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Sample records for continuous insulin infusion

  1. Continuous subcutaneous insulin infusion: practical issues

    PubMed Central

    Saboo, Banshi D.; Talaviya, Praful A.

    2012-01-01

    The growing number of individuals with diabetes mellitus has prompted new way of treating these patients, continuous subcutaneous insulin infusion (CSII) or insulin pump therapy is an increasingly form of intensive insulin therapy. An increasing number of individuals with diabetes mellitus individuals of all ages have started using insulin pump therapy. Not everyone is a good candidate for insulin pump therapy, and the clinician needs to be able to determine which patients are able to master the techniques required and to watch for the adverse reactions that may develop. Insulin pump increases quality of life of patient with diabetes mellitus with increasing satisfaction with treatment and decrease impact of diabetes mellitus. Manual errors by insulin pump users may lead to hypo or hyperglycemia, resulting into diabetic ketoacidosis (DKA) sometimes. Some of practical aspect is associated with insulin pump therapy such as selection of candidates, handling of pump and selection of site, and pump setting, henceforth this review is prepared to explore and solve the practical problems or issues associated with pump therapy. PMID:23565394

  2. Insulin Infusion Set: The Achilles Heel of Continuous Subcutaneous Insulin Infusion

    PubMed Central

    Heinemann, Lutz; Krinelke, Lars

    2012-01-01

    Continuous subcutaneous insulin infusion from an insulin pump depends on reliable transfer of the pumped insulin to the subcutaneous insulin depot by means of an insulin infusion set (IIS). Despite their widespread use, the published knowledge about IISs and related issues regarding the impact of placement and wear time on insulin absorption/insulin action is relatively small. We also have to acknowledge that our knowledge is limited with regard to how often patients encounter issues with IISs. Reading pump wearer blogs, for instance, suggests that these are a frequent source of trouble. There are no prospective clinical studies available on current IIS and insulin formulations that provide representative data on the type and frequency of issues with infusion sets. The introduction of new IISs and patch pumps may foster a reassessment of available products and of patient problems related to their use. The aim of this review is to summarize the current knowledge and recommendations about IISs and to highlight potential directions of IIS development in order to make insulin absorption safer and more efficient. PMID:22920824

  3. Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics.

    PubMed

    Pozzilli, Paolo; Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz-Chobot, Przemyslawa; Renard, Eric

    2016-01-01

    The level of glycaemic control necessary to achieve optimal short-term and long-term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid-acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health-related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid-acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost-effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid-acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients

  4. Complications of continuous intraperitoneal insulin infusion with an implantable pump

    PubMed Central

    van Dijk, Peter R; Logtenberg, Susan JJ; Groenier, Klaas H; Haveman, Jan Willem; Kleefstra, Nanno; Bilo, Henk JG

    2012-01-01

    AIM: To monitor the course of continuous intraperitoneal insulin infusion (CIPII) and to gain more insight into possible complications. METHODS: A retrospective, longitudinal observational cohort study in patients with type 1 diabetes mellitus (T1DM) was performed. Only patients with “brittle” T1DM who started CIPII between January 1, 2000 and June 1, 2011, and were treated in the only centre in The Netherlands providing CIPII treatment (Isala clinics, Zwolle) were eligible for inclusion. Outcomes were defined as operation-free period (OFP), rate and type of complications. Subanalyses were made between patients starting CIPII from 2000 to 2007 and from 2007 onwards in order to study possible changes over time in complications and/or OFP. The OFP was calculated as the time from initial implantation to the date of first documented re-operation. If patients had not experienced an operation, their data were recorded at the date of last follow up or death. Kaplan-Meier curves were constructed to visualize the OFP. A (two-sided) P value of less than 0.05 was considered statistically significant. RESULTS: Fifty-seven patients were treated with CIPII, although one patient was excluded from analyses because of self-induced complications. In the remaining 56 patients, 70 complications occurred during 283 patient years. Catheter occlusion (32.9%), pump dysfunction (17.1%), pain at the pump site (15.7%) and infections (10.0%) were the most frequent complications. This resulted in a median OFP of 4.5 years (95% confidence interval 4.1-4.8 years) without any difference between the time periods. Fifty re-operations were performed because of complications, one per 5.6 patient years, with a decrease in pump dysfunction (P = 0.04) and pump explantations (P = 0.02) after 2007. In total, 9 episodes of ketoacidosis occurred during follow up and there were 69 hospital re-admissions, with a median duration of 6 d. CIPII was ceased in five patients due to recurrent infections (n = 2

  5. Practical aspects and considerations when switching between continuous subcutaneous insulin infusion and multiple daily injections.

    PubMed

    Meneghini, Luigi; Sparrow-Bodenmiller, Jane

    2010-06-01

    Insulin pump therapy is considered the gold standard for insulin management in patients requiring full physiologic insulin replacement. Compared to traditional delivery of short- and long-acting insulin preparations by multiple daily insulin injections, delivery of insulin via continuous subcutaneous infusion brings with it several advantages, which in the past have translated into better glycemic control and treatment satisfaction. Delivery of insulin via pump reduces the number needle insertions (from four or five per day to once every 2-3 days), allows for greater flexibility of insulin delivery with regard to both the basal and prandial component, facilitates portability of the insulin preparation, and allows for more accurate dosing. Continuous subcutaneous insulin infusion does have some drawbacks, including a greater risk of inadvertent insulin non-delivery, greater costs of therapy, and the need to be "tethered" with some systems that might be considered "burdensome" or even undesirable to some patients. For the most part patients who initiate insulin pump therapy are satisfied and continue using the technology, but there might be instances that arise that require the re-introduction of insulin delivery by pen or syringe. This article will review some of the reasons and strategies for switching from one mode of delivery to the other. PMID:20515298

  6. Feasibility of continuous subcutaneous insulin infusion in young diabetic patients.

    PubMed

    Levy-Marchal, C; Czernichow, P

    1988-01-01

    Seven diabetic children (age: 8-12 y.) participated in a study comparing CSII and conventional treatment (CT) under the same monitoring and supervision for a year. The aim of the study was to explore the feasibility, the risks and the results on the glycemic control of CSII. Mean HbAlC fell from 9.3 +/- 2.1% to 7.3 +/- 1.4% (p less than 0.001) after the first month of CSII, remaining stable thereafter and with marginally lower, daily insulin requirements. There was a trend for HbAlc to increase, (HbAlC = 8.6 +/- 1.8%) under conventional treatment. The individual means of premeal capillary blood glucose concentrations were lower under CSII than under CT, but exhibited large variability under both treatments. Symptomatic hypoglycemia was as frequent under CSII as under CT. Ketonuria occurred frequently after the night basal infusion, but was of moderate clinical relevance and mainly due to technical problems. All seven children completed the trial; 4 of them chose to return to pump treatment. No psychologically adverse effects were noted. They all liked the flexibility of lifestyle afforded by CSII, and were generally compliant with the guidelines of this regimen. The pump itself was a valuable educational tool for the children and their families. However, CSII was recognized as individually demanding. This study demonstrates the feasibility of CSII in prepubertal children, and its impact on the glycemic control. The risks of this form of intensified treatment were limited by the strict monitoring and medical supervision provided by a specialized team. PMID:3042484

  7. An experimental study of pulsed micro-flows pertinent to continuous subcutaneous insulin infusion therapy

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Demuren, Ayodeji; Gyuricsko, Eric; Hu, Hui

    2011-07-01

    An experimental study was conducted to investigate the unsteady micro-flow driven by an insulin pump commonly used in continuous subcutaneous insulin infusion (CSII) therapy. A microscopic particle image velocimetry (PIV) system was used to characterize the transient behavior of the micro-flow upon the pulsed excitation of the insulin pump in order to elucidate the underlying physics for a better understanding of the microphysical process associated with the insulin delivery in CSII therapy. The effects of air bubbles entrained inside the micro-sized CSII tubing system on the insulin delivery process were also assessed based on the micro-PIV measurements. While most solutions to insulin occlusion-related problems are currently based on clinical trials, the findings derived from the present study can be used to provide a better guidance for the troubleshooting of insulin occlusion in CSII therapy.

  8. 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…

  9. A Review of Insulin-Dosing Formulas for Continuous Subcutaneous Insulin Infusion (CSII) for Adults with Type 1 Diabetes.

    PubMed

    King, Allen B; Kuroda, Akio; Matsuhisa, Munehide; Hobbs, Todd

    2016-09-01

    Dosing guidelines for patients with type 1 diabetes using continuous subcutaneous insulin infusion (CSII), which are historically based on clinical experience and retrospective studies of patients consuming an American diet, recommend that basal insulin should represent approximately 50 % of the total daily dose (TDD). Recent prospective studies in the USA and Japan conclude that the more appropriate proportion is closer to 30-40 % of TDD. In addition, currently used formulas for calculating the carbohydrate-to-insulin ratio (CIR) and correction factor (CF) may lead to underdosing of bolus insulin by as much as 12.8-50 % for a hypothetical patient. The discrepancies between traditional formulas and data from newer studies can be accounted for by the more rigorous design of the newer studies (e.g., prospective design, controlled diets, meal omission, and frequent glucose monitoring). International differences in diet composition may also be important to consider when developing dosing recommendations for CSII. PMID:27457238

  10. Position Statement on the management of continuous subcutaneous insulin infusion (CSII): The Italian Lazio experience.

    PubMed

    Maurizi, Anna R; Suraci, Concetta; Pitocco, Dario; Schiaffini, Riccardo; Tubili, Claudio; Morviducci, Lelio; Giordano, Renato; Manfrini, Silvia; Lauro, Davide; Frontoni, Simona; Pozzilli, Paolo; Buzzetti, Raffaella

    2016-01-01

    This document has been developed by a group of Italian diabetologists with extensive experience in continuous subcutaneous insulin infusion (CSII) therapy to provide indications for the clinical management of CSII in diabetic patients (both type 1 and type 2) based on delivery mode operating in Italy. Although the potential benefits of pump therapy in achieving glycemic goals is now accepted, such results cannot be obtained without specific knowledge and skills being conveyed to patients during ad hoc educational training. To ensure that these new technologies reach their full effectiveness, as demonstrated theoretically and clinically, a careful assessment of the overall therapeutic and educational process is required, in both qualitative and quantitative terms. Therefore, to ensure the cost-effectiveness of insulin pump therapy and to justify reimbursement of therapy costs by the National Health System in Italy, in this article we present a model for diabetes and healthcare centers to follow that provides for different levels of expertise in the field of CSII therapy. This model will guarantee the provision of excellent care during insulin pump therapies, thus representing the basis for a successful outcome and expansion of this form of insulin treatment in patients with diabetes while also keeping costs under control. PMID:26118939

  11. Long-acting insulin analogues (insulin glargine or determir) and continuous subcutaneous insulin infusion in the treatment of type 1 diabetes mellitus in the paediatric population.

    PubMed

    Barrio Castellanos, Raquel

    2005-12-01

    Despite many improvements in the treatment of type 1 diabetes mellitus (DM1), the non-physiological time-action profiles of conventional insulins remain a significant obstacle. In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular and NPH insulin. The rapid insulin analogs used as prandial and the long-acting insulin analogs used as basal simulate physiological insulin profiles more closely than the older conventional insulins. The efficacy of insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in DM1 has been established in pediatric patients. Insulin pumps have improved since they were first introduced. CSII therapy may provide an effective alternative for selected pediatric patients with DM1. In most studies at pediatric age, CSII therapy resulted in a improvement in HbA1c, a decreased rate of hypoglycemia without an abnormal increase in BMI, and without adversely affecting psychosocial outcomes in children and adolescents with DM1. PMID:16398447

  12. Development of Gendine-Coated Cannula for Continuous Subcutaneous Insulin Infusion for Extended Use

    PubMed Central

    Jamal, Mohamed A.; Garoge, Kumait; Rosenblatt, Joel S.; Hachem, Ray Y.

    2015-01-01

    Continuous subcutaneous insulin infusion (CSII) using pumps is a widely used method for insulin therapy in patients with diabetes mellitus. Among the major factors that usually lead to the discontinuation of CSII are CSII set-related issues, including infection at the infusion site. The American Diabetic Association currently recommends rotating sites every 2 to 3 days. This recommendation adds cost and creates inconvenience. Therefore, in order to prevent infections and extend the duration between insertion site changes, we developed a Teflon cannula coated with a combination of gentian violet and chlorhexidine (gendine) and tested its antimicrobial efficacy against different pathogens. The cannulas were coated with gendine on the exterior surface and dried. The efficacy and durability of gendine-coated cannulas were determined against methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, methicillin-susceptible S. aureus, Streptococcus pyogenes, vancomycin-resistant enterococci, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Candida glabrata using a biofilm colonization method. The cytotoxicity of gendine was assessed against mouse fibroblast cell lines. The gendine-coated cannulas showed complete prevention of biofilm colonization of all organisms tested for up to 2 weeks (P < 0.0001) compared to that with the uncoated control. A gendine-coated catheter against mouse fibroblast cells was shown to be noncytotoxic. Our in vitro results show that a novel gendine cannula is highly effective in completely inhibiting the biofilm of multidrug-resistant pathogens for up to 2 weeks and may have potential clinical applications, such as prolonged use, cost reduction, and lower infection rate. PMID:25941227

  13. Development of Gendine-Coated Cannula for Continuous Subcutaneous Insulin Infusion for Extended Use.

    PubMed

    Jamal, Mohamed A; Garoge, Kumait; Rosenblatt, Joel S; Hachem, Ray Y; Raad, Issam I

    2015-08-01

    Continuous subcutaneous insulin infusion (CSII) using pumps is a widely used method for insulin therapy in patients with diabetes mellitus. Among the major factors that usually lead to the discontinuation of CSII are CSII set-related issues, including infection at the infusion site. The American Diabetic Association currently recommends rotating sites every 2 to 3 days. This recommendation adds cost and creates inconvenience. Therefore, in order to prevent infections and extend the duration between insertion site changes, we developed a Teflon cannula coated with a combination of gentian violet and chlorhexidine (gendine) and tested its antimicrobial efficacy against different pathogens. The cannulas were coated with gendine on the exterior surface and dried. The efficacy and durability of gendine-coated cannulas were determined against methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, methicillin-susceptible S. aureus, Streptococcus pyogenes, vancomycin-resistant enterococci, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Candida glabrata using a biofilm colonization method. The cytotoxicity of gendine was assessed against mouse fibroblast cell lines. The gendine-coated cannulas showed complete prevention of biofilm colonization of all organisms tested for up to 2 weeks (P < 0.0001) compared to that with the uncoated control. A gendine-coated catheter against mouse fibroblast cells was shown to be noncytotoxic. Our in vitro results show that a novel gendine cannula is highly effective in completely inhibiting the biofilm of multidrug-resistant pathogens for up to 2 weeks and may have potential clinical applications, such as prolonged use, cost reduction, and lower infection rate. PMID:25941227

  14. Carbohydrate-to-Insulin Ratio in a Mediterranean Population of Type 1 Diabetic Patients on Continuous Subcutaneous Insulin Infusion Therapy

    PubMed Central

    Alcántara-Aragón, Valeria; Gonzalez, Cintia; Corcoy, Rosa; Ubeda, Justa; Chico, Ana

    2014-01-01

    Background: The carbohydrate-to-insulin ratio (CIR) is initially calculated from the total daily insulin dose (TDID). However, CIR likely presents variations owing to different population characteristics and intraday variations not being taken into account by most formulas. No information is available concerning the Mediterranean population. We investigated the CIR used by patients with type 1 diabetes (T1DM) using continuous subcutaneous insulin infusion (CSII) therapy in a Mediterranean area, to identify possible intraday variations and establish an adequate formula to calculate CIR. Methods: Data from 170 T1DM patients from Barcelona were obtained retrospectively from the Spanish National Registry of CSII Therapy (SNR-CSII). Theoretical CIR was calculated using the formula: 500 divided by TDID. This theoretical CIR was compared to the real CIR. Results: The real CIR was also compared between main meals. Patients with HbA1c < 7% (n = 44) were considered a reference group for accurate bolus calculation and were analyzed as a subgroup. The real CIR used was 11.5 g/UI for breakfast, 12 g/UI for lunch, and 13.3 g/UI for dinner. CIR obtained by the 500/TDID formula for all meals was 15.5 g/UI. We obtained similar results for the group with HbA1c < 7%. The real CIR differed significantly from the theoretical CIR values and between breakfast and the other main meals (P < .005). Conclusions: CIR in our population was significantly lower for breakfast than for other meals. CIR using the 500/TDID formula underestimated prandial insulin requirements. A calculation of 350/TDID for breakfast and 400/TDID for lunch and dinner would be more appropriate for this population. PMID:25519294

  15. Effect of optimal glycaemic control with continuous subcutaneous insulin infusion on energy expenditure in type I diabetes mellitus.

    PubMed Central

    Leslie, P; Jung, R T; Isles, T E; Baty, J; Newton, R W; Illingworth, P

    1986-01-01

    To assess the role of insulin in the control of body weight energy expenditure was measured by indirect calorimetry in eight patients of normal weight with type I diabetes initially while poorly controlled during conventional insulin treatment and later during optimal glycaemic control achieved by using the continuous subcutaneous insulin infusion pump. Their response to seven days of fat supplementation was also assessed and the results compared with those in eight non-diabetic subjects. After a mean of 5.3 months of continuous subcutaneous insulin infusion the diabetic subjects had gained on average 3.5 kg. In the poorly controlled diabetic state the resting metabolic rate was raised but decreased by a mean of 374 kJ (90 kcal) per 24 hours with optimal glycaemic control. The thermic response to infused noradrenaline was reduced by 59% in the diabetic subjects, was not improved by continuous subcutaneous insulin infusion, but was improved when three of the subjects were given metformin in addition. The diabetic subjects had no abnormality in the thermic response to a meal while taking their usual diabetic diet. During fat supplementation, however, this thermic response was reduced when glycaemic control was poor but not when control was precise. Fat supplementation did not alter the resting metabolic rate or the reduced noradrenergic thermic response in the diabetic subjects. These findings suggest that precise glycaemic control could produce weight gain if energy intake remained unaltered, for diabetic subjects do not compensate for the decrease in metabolic rate by an increase in noradrenergic and dietary thermic responses. Also precise glycaemic control using continuous subcutaneous insulin infusion does not correct all the metabolic abnormalities of diabetes mellitus. PMID:3094802

  16. Opinions and Satisfaction Regarding Continuous Subcutaneous Insulin Infusion Therapy in Adult Patients with Type 1 Diabetes

    PubMed Central

    Nishio, Ikuko; Chujo, Masami; Ohkura, Tsuyoshi; Kataoka, Hideyuki

    2015-01-01

    Background This study examined the treatment satisfaction of type 1 diabetic patients undergoing continuous subcutaneous insulin infusion (CSII) therapy, and patients’ thoughts regarding CSII. Methods We provided a self-administered questionnaire survey over the internet. Participants were 106 individuals with type-one diabetes aged 20 years or older, undergoing CSII. The survey examined patients’ treatment satisfaction, and their thoughts regarding CSII. Descriptive statistics were calculated. We compared relationships between treatment satisfaction and other variables using the Kruskal-Wallis rank sum test, and performed content analysis on participants’ thoughts regarding CSII. Results Regarding treatment satisfaction, the response, “neither of them” was the most frequent. Comparing relationships between treatment satisfaction and other variables, significant differences were found for the variables “age,” “presence of dissatisfaction regarding doctors’ response,” and “presence of a significant medical expense burden.” Participants’ thoughts regarding CSII were classified into 10 categories. Conclusion Participants expressed positive evaluations, such as that their blood sugar control had improved due to CSII, and that they perceived improvement in their health. Participants also expressed negative evaluations, however, such as that medical expenses resulting from CSII were high, and that these expenses may cause distress and future economic insecurity. In future, patients may benefit from nursing support that allows patients to confidently continue with CSII. PMID:26538796

  17. Type 1 Diabetes Patients Using Continuous Subcutaneous Insulin Infusion Therapy: Feeling Burdened Correlated with Factors

    PubMed Central

    Nishio, Ikuko; Chujo, Masami

    2015-01-01

    Background The purpose of this study was to investigate factors related to feelings of being burdened in type 1 diabetes patients using continuous subcutaneous insulin infusion (CSII) therapy. Methods Participants were 106 subscribers to the Diabetes Network’s e-mail newsletter. An online survey was used. Eligible participants were aged at least 20 years, had type 1 diabetes, and were using CSII. Survey questions concerned whether participants found CSII burdensome, and seven potential reasons for feelings of burden. Analysis calculated correlations among participants’ demographic and treatment-related factors, and among participants’ reasons for feeling CSII to be burdensome. Results Regarding demographic and treatment-related factors, gender was found to be weakly negatively correlated with the following variables: employment status, and whether participants had discussed their concerns with a doctor. Employment status was found to be weakly correlated with diabetes duration; employment status and diabetes duration were found to be weakly correlated with age. Regarding reasons for finding CSII therapy burdensome, “It takes too much time” was found to be strongly positively correlated with “It interferes with work responsibilities”; 16 weak positive correlations were also found. Conclusion To explain our results, we suggest that medical expenses, glycemic control, scheduling outpatient visits around home and work responsibilities, and interacting with medical staff may have caused participants to find CSII therapy burdensome. Most participants had never discussed their treatment concerns with a doctor. This suggests that nurses may be able to mitigate feeling burdened in participants using CSII therapy. PMID:26538798

  18. A Comparison of Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Insulin Injection in Children with Type I Diabetes in Kuwait: Glycemic Control, Insulin Requirement, and BMI

    PubMed Central

    Mousa, Mohammad; Al-Mahdi, Maria; Al-Sanaa, Hala; Al-Kandari, Hessa

    2015-01-01

    Objective Continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) are two methods currently used to manage type I diabetes mellitus (T1DM). Here we compare our experiences with CSII and MDI in a large cohort of pediatric patients in Kuwait. Methods Data on 326 patients with T1DM who were started on CSII between 2007 and 2012 were retrospectively compared with those of 326 patients on MDI. They were matched for sex, age at diagnosis, T1DM duration, glycemic control, insulin requirement, and body mass index (BMI). Data were collected at baseline and every three months and included glycated hemoglobin (HbA1c), insulin dose, and adverse events (severe hypoglycemia, diabetic ketoacidosis, and skin problems). Results The main reason for switching to CSII was to achieve better glycemic control (37%), followed by reducing hypoglycemia, and improving the quality of life (13.3% each). Although HbA1c decrease was most significant in the first year, it continued to be significantly lower in the CSII group compared to the MDI throughout the study period. Total daily insulin requirements were significantly lower in the CSII group. BMI increased in both groups, but the difference was significant only at the end of the fifth year. There was no significant change in the rate of diabetic ketoacidosis in either group. The CSII patients had more severe hypoglycemic episodes at baseline; however, it significantly decreased throughout the study period. Only five patients discontinued CSII therapy and two of these restarted within three months. Conclusion CSII is a safe intensive insulin therapy in youngsters with T1DM and achieved markedly fewer severe hypoglycemic episodes and lower daily insulin requirements PMID:26421114

  19. Continuous Subcutaneous Insulin Infusion (CSII) Pumps for Type 1 and Type 2 Adult Diabetic Populations

    PubMed Central

    2009-01-01

    Executive Summary In June 2008, the Medical Advisory Secretariat began work on the Diabetes Strategy Evidence Project, an evidence-based review of the literature surrounding strategies for successful management and treatment of diabetes. This project came about when the Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the Ministry’s newly released Diabetes Strategy. After an initial review of the strategy and consultation with experts, the secretariat identified five key areas in which evidence was needed. Evidence-based analyses have been prepared for each of these five areas: insulin pumps, behavioural interventions, bariatric surgery, home telemonitoring, and community based care. For each area, an economic analysis was completed where appropriate and is described in a separate report. To review these titles within the Diabetes Strategy Evidence series, please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html, Diabetes Strategy Evidence Platform: Summary of Evidence-Based Analyses Continuous Subcutaneous Insulin Infusion Pumps for Type 1 and Type 2 Adult Diabetics: An Evidence-Based Analysis Behavioural Interventions for Type 2 Diabetes: An Evidence-Based Analysis Bariatric Surgery for People with Diabetes and Morbid Obesity: An Evidence-Based Summary Community-Based Care for the Management of Type 2 Diabetes: An Evidence-Based Analysis Home Telemonitoring for Type 2 Diabetes: An Evidence-Based Analysis Application of the Ontario Diabetes Economic Model (ODEM) to Determine the Cost-effectiveness and Budget Impact of Selected Type 2 Diabetes Interventions in Ontario Objective The objective of this analysis is to review the efficacy of continuous subcutaneous insulin infusion (CSII) pumps as compared to multiple daily injections (MDI) for the type 1 and type 2 adult diabetics. Clinical Need

  20. Update on a Quality Initiative to Standardize Perioperative Care for Continuous Subcutaneous Insulin Infusion Therapy

    PubMed Central

    Mackey, Patricia A.; Thompson, Bithika M.; Boyle, Mary E.; Apsey, Heidi A.; Seifert, Karen M.; Schlinkert, Richard T.; Stearns, Joshua D.; Cook, Curtiss B.

    2015-01-01

    Objective: The objective of the analysis was to review the effectiveness of a care process model (CPM) developed to guide management of patients on insulin pump therapy undergoing elective surgical procedures. Methods: Electronic medical records were reviewed to assess the impact of the CPM on documentation of insulin pump status, glucose monitoring, and safety during the perioperative phase of care. Post-CPM care was compared with management provided before CPM implementation. Results: We reviewed 45 cases on insulin pump therapy in the pre-CPM cohort and 106 in the post-CPM cohort. Demographic characteristics, categories of surgery, and perioperative times were not significantly different between the 2 groups. Recommended hemoglobin A1c monitoring occurred in 73% of cases in the pre-CPM cohort but improved to 94% in the post-CPM group (P < .01). There was a higher frequency of documentation of the insulin pump during the preoperative, intraoperative, and postanesthesia care unit segments of care in the post- vs pre-CPM periods (all P < .01). The number of cases with intraoperative glucose monitoring increased (57% pre-CPM vs 81% post-CPM; P < .01). Glycemic control was comparable between the 2 CPM periods. Hypoglycemia was rare, with only 3 episodes in the pre-CPM group and 4 in the post-CPM. No adverse events associated with perioperative insulin pump use were observed. Conclusions: This analysis adds to previous data on use of insulin pump therapy during the perioperative period. Some processes require additional attention, but data continue to indicate that a standardized approach to care can lead to a successful and safe transition of insulin pump therapy throughout the perioperative period. PMID:26092687

  1. Comparative Effectiveness of Continuous Subcutaneous Insulin Infusion Using Insulin Analogs and Multiple Daily Injections in Pregnant Women with Diabetes Mellitus: A Systematic Review and Meta-Analysis

    PubMed Central

    Maruthur, Nisa M.; Nicholson, Wanda K.; Yeh, Hsin-Chieh; Brown, Todd; Suh, Yong; Wilson, Lisa M.; Nannes, Elisabeth B.; Berger, Zack; Bass, Eric B.; Golden, Sherita Hill

    2015-01-01

    Abstract We systematically reviewed the effectiveness and safety of continuous subcutaneous insulin infusion (CSII) with insulin analogs compared with multiple daily injections (MDI) in pregnant women with diabetes mellitus. We searched Medline®, Embase®, and the Cochrane Central Register of Controlled Trials through May 2013. Studies comparing CSII with MDI in pregnant women with diabetes mellitus were included. Studies using regular insulin CSII were excluded. We conducted meta-analyses where there were two or more comparable studies based on the type of insulin used in the MDI arm. Seven cohort studies of pregnant women with type 1 diabetes reported improvement in hemoglobin A1c (HbA1c) in both groups. Meta-analysis showed no difference in maternal and fetal outcomes for CSII versus MDI. Results were similar when CSII was compared with MDI with insulin analogs or regular insulin. Studies had moderate to high risk bias with incomplete descriptions of study methodology, populations, treatments, follow up, and outcomes. We conclude that observational studies reported similar improvements in HbA1c with CSII and MDI during pregnancy, but evidence was insufficient to rule out possible important differences between CSII and MDI for maternal and fetal outcomes. This highlights the need for future studies to examine the effectiveness and safety of CSII with insulin analogs and MDI in pregnant women with diabetes mellitus. PMID:25713996

  2. Comparison of a Multiple Daily Insulin Injection Regimen (Glargine or Detemir Once Daily Plus Prandial Insulin Aspart) and Continuous Subcutaneous Insulin Infusion (Aspart) in Short-Term Intensive Insulin Therapy for Poorly Controlled Type 2 Diabetes Patients

    PubMed Central

    Lv, Wen-shan; Li, Li; Wen, Jun-ping; Pan, Rong-fang; Sun, Rui-xia; Wang, Jing; Xian, Yu-xin; Cao, Cai-xia; Gao, Yan-yan

    2013-01-01

    Aims. To examine the potential differences between multiple daily injection (MDI) regimens based on new long-acting insulin analogues (glargine or detemir) plus prandial insulin aspart and continuous subcutaneous insulin aspart infusion (CSII) in patients with poorly controlled type 2 diabetes. Methods. Patients (n = 119) with poorly controlled type 2 diabetes of a duration exceeding five years were randomly assigned into three groups: Group A treated with CSII using insulin aspart; Group B treated with glargine-based MDI and Group C treated with detemir-based MDI. Results. Good glycemic control was achieved by patients in Group A in a significantly shorter duration than patients in Groups B and C. Total daily insulin, basal insulin dose and dose per kg body weight in Group A were significantly less than those in Groups B and C. Daily blood glucose fluctuation in Group A was significantly less than that in Groups B and C. There were no differences between Groups B and C. Conclusions. Aspart-based CSII may achieve good blood glucose control with less insulin doses over a shorter period compared with glargine or detemir-based MDI. No differences between glargine- and detemir-based MDI were detected in poorly controlled subjects with type 2 diabetes. PMID:23737776

  3. 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. PMID:3297580

  4. Designing the modern pump: engineering aspects of continuous subcutaneous insulin infusion software.

    PubMed

    Welsh, John B; Vargas, Steven; Williams, Gary; Moberg, Sheldon

    2010-06-01

    Insulin delivery systems attracted the efforts of biological, mechanical, electrical, and software engineers well before they were commercially viable. The introduction of the first commercial insulin pump in 1983 represents an enduring milestone in the history of diabetes management. Since then, pumps have become much more than motorized syringes and have assumed a central role in diabetes management by housing data on insulin delivery and glucose readings, assisting in bolus estimation, and interfacing smoothly with humans and compatible devices. Ensuring the integrity of the embedded software that controls these devices is critical to patient safety and regulatory compliance. As pumps and related devices evolve, software engineers will face challenges and opportunities in designing pumps that are safe, reliable, and feature-rich. The pumps and related systems must also satisfy end users, healthcare providers, and regulatory authorities. In particular, pumps that are combined with glucose sensors and appropriate algorithms will provide the basis for increasingly safe and precise automated insulin delivery-essential steps to developing a fully closed-loop system. PMID:20515305

  5. Short-Term Continuous Subcutaneous Insulin Infusion Combined with Insulin Sensitizers Rosiglitazone, Metformin, or Antioxidant α-Lipoic Acid in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

    PubMed Central

    Huang, Zhimin; Wan, Xuesi; Liu, Juan; Deng, Wanping; Chen, Ailing; Liu, Liehua; Liu, Jianbin; Wei, Guohong; Li, Hai; Fang, Donghong

    2013-01-01

    Abstract Background Short-term continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes has been proved effective in improving metabolic control and β-cell function, thus inducing long-term drug-free remission. A randomized controlled trial was conducted to investigate whether CSII in combination with rosiglitazone, metformin, or α-lipoic acid separately brings about extra benefits. Patients and Methods One hundred sixty patients with newly diagnosed type 2 diabetes were randomized to one of four treatment groups: CSII alone, CSII in combination with rosiglitazone or metformin for 3 months, or CSII with α-lipoic acid intravenous infusion for 2 weeks. Duration of CSII treatment was identical in the four groups. Glucose and lipid profiles, homeostasis model assessment (HOMA) indices, acute insulin response (AIR), intramyocellular lipid (IMCL) level, and malondialdehyde level were compared before and after intervention. Results The near-normoglycemia rate at the third month in CSII alone and that in combination with rosiglitazone, metformin, or α-lipoic acid was 72.5%, 87.5%, 90%, and 75%, respectively (metformin group vs. CSII alone, P=0.045). The metformin group achieved euglycemia in a shorter time (2.6±1.3 vs. 3.7±1.8 days, P=0.020) with less daily insulin dosage and was more powerful in lowering total cholesterol, increasing AIR and HOMA β-cell function, whereas reduction of IMCL in the soleus was more obvious in the rosiglitazone group but not in the metformin group. The efficacy of combination with α-lipoic acid was similar to that of CSII alone. Conclusions Short-term CSII in combination with rosiglitazone or metformin is superior to CSII alone, yet the efficacy of the two differs in some way, whereas that with α-lipoic acid might not have an additive effect. PMID:23991629

  6. Continuous intraperitoneal insulin infusion in type 1 diabetes: a 6-year post-trial follow-up

    PubMed Central

    2014-01-01

    Background Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a treatment option for patients with type 1 diabetes mellitus (T1DM). Aim of the present study was to describe the long-term course of glycaemic control, complications, health related quality of life (HRQOL) and treatment satisfaction among T1DM patients treated with CIPII. Methods Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) therapy in 2006 were followed until 2012. Laboratory, continuous glucose monitoring, HRQOL and treatment satisfaction measurements were performed at the start of the study, the end of the SC-, the end of the CIPII treatment phase in 2006 and during CIPII therapy in 2012. Linear mixed models were used to calculate estimated values and to test differences between the moments in time. Results In 2012, more time was spent in hyperglycaemia than after the CIPII treatment phase in 2006: 37% (95% CI 29, 44) vs. 55% (95% CI 48, 63), mean difference 19.8% (95% CI 3.0, 36.6). HbA1c was 65 mmol/mol (95% CI 60, 71) at the end of the SC treatment phase in 2006, 58 mmol/mol (95% CI 53, 64) at the end of the CIPII treatment phase and 65 mmol/mol (95% CI 60, 71) in 2012, respectively (p > 0.05). In 2012, the median number of grade 2 hypoglycaemic events per week (1 (95% CI 0, 2)) was still significantly lower than during prior SC therapy (3 (95% CI 2, 4)): mean change -1.8 (95% CI -3.4, -0.4). Treatment satisfaction with CIPII was better than with SC insulin therapy and HRQOL remained stable. Pump or catheter dysfunction of the necessitated re-operation in 7 patients. No mortality was reported. Conclusions After 6 years of CIPII treatment, glycaemic regulation is stable and the number of hypoglycaemic events decreased compared to SC insulin therapy. Treatment satisfaction with CIPII is superior to SC insulin therapy, HRQOL is stable and complications are scarce. CIPII is a safe and effective treatment

  7. Progression of diabetic retinopathy and changes in serum insulin-like growth factor I (IGF I) during continuous subcutaneous insulin infusion (CSII).

    PubMed

    Hyer, S L; Sharp, P S; Sleightholm, M; Burrin, J M; Kohner, E M

    1989-01-01

    The rise in serum IGF I concentration during continuous subcutaneous insulin infusion (CSII) may be a contributory factor in the deterioration of diabetic retinopathy that sometimes occurs during this treatment but the relation of serum levels to the severity of retinopathy has not been previously studied. In twelve non-obese insulin dependent diabetics (age range: 22-41 yrs) with mean +/- SD duration of diabetes: 14.8 +/- 4.7 yrs, serum IGF I concentration, HbA1 and retinopathy score were estimated prospectively over twelve months following the institution of CSII therapy. After four months of treatment, eight patients showed deterioration of retinopathy by at least one level of severity. Serum IGF I concentration rose from a mean +/- SEM of 155 +/- 17.7 micrograms/l at entry to 199 +/- 23.1 micrograms/l at four months and by twelve months had returned to near initial values 163 +/- 17.4 micrograms/l. There was however, no significant correlation between retinopathy score and serum IGF I level by analysis of variance for the whole group, or in the group of diabetics whose retinopathy deteriorated. The rise in IGF I concentration over the first four months and subsequent decline in IGF I values over the next eight months was inversely related to HbA1 concentration (r = -0.58; P less than 0.05). One patient with early ischaemic retinopathy on entry, experienced a marked rise in serum IGF I corresponding to a rapid tightening of glycaemic control. At four months she developed florid proliferative changes requiring panretinal laser therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2925151

  8. The Variable Rate Intravenous Insulin Infusion Protocol.

    PubMed

    Collard, Benjamin; Sturgeon, Jonathan; Patel, Natasha; Asharia, Shabbar

    2014-01-01

    Insulin use among inpatients is high and associated with severe and regular medication errors. An initial baseline audit showed a wide variation in the prescription of intravenous insulin within the trust. These included variation in the choice of fluid prescribed, electrolyte levels not consistently checked, handwritten illegible prescriptions, and varying parameters set for adjustment of the prescription. A Variable Rate Intravenous Insulin Infusion protocol (VRIII)) was introduced to standardize intravenous insulin prescription throughout the trust by all members of the clinical team. We looked at and measured uptake and effects of the VRIII protocol in improving standardization of insulin prescription for inpatients on insulin at St George's NHS trust. The protocol was uploaded to the intranet to allow access 24 hours a day and the staff educated about it. The VRIII protocol was routinely used successfully throughout the trust. Any initial problems were addressed through education of clinical staff. The protocol has shown decreased prescribing and administrative errors, whilst demonstrating good glucose and electrolyte control. Use of a standardized protocol helps reduce medication errors and demonstrates good glycaemic control. Regular and continued education of clinical staff is necessary to maintain its efficacy. PMID:26734228

  9. Attitudes Toward Diabetes Affect Maintenance of Drug-Free Remission in Patients With Newly Diagnosed Type 2 Diabetes After Short-Term Continuous Subcutaneous Insulin Infusion Treatment

    PubMed Central

    Chen, Ailing; Huang, Zhimin; Wan, Xuesi; Deng, Wanping; Wu, Jiyan; Li, Licheng; Cai, Qiuling; Xiao, Haipeng; Li, Yanbing

    2012-01-01

    OBJECTIVE Short-term intensive insulin treatment in patients with newly diagnosed type 2 diabetes can improve β-cell function and insulin sensitivity, which results in long-term remission without need for further antidiabetes medication. Patient attitudes toward their disease were assessed using the Diabetes Care Profile (DCP) tool to evaluate the potential impact on maintaining long-term remission. RESEARCH DESIGN AND METHODS Newly diagnosed patients with type 2 diabetes were recruited and treated with continuous subcutaneous insulin infusion (CSII) for 2–3 weeks. They were also invited to participate in diabetes self-management intervention during hospitalization and complete a DCP questionnaire on attitudes toward diabetes at baseline and 3, 6, and 12 months after suspension of CSII. RESULTS Near normoglycemia was achieved by 118 patients after short-term CSII, with 65 remaining in drug-free remission for >1 year. They had significantly better glycemic control and greater restoration of acute insulin response after CSII as well as higher educational attainment compared with patients experiencing relapse. They also achieved higher scores in positive attitude, (belief in) importance of care, care ability, self-care adherence, and less negative attitude. Differences between the two groups became greater over time. Cox proportional hazards model analysis indicated that greater self-care adherence (hazard ratio 0.184, P < 0.001) and homeostasis model assessment of insulin resistance before treatment (0.854, P = 0.053) were independent predictors for long-term remission, whereas elevated 2-h postprandial plasma glucose after CSII (1.156, P = 0.015) was a risk factor for relapse. CONCLUSIONS Attitudes toward diabetes affect long-term drug-free remission in newly diagnosed patients with type 2 diabetes after short-term CSII. PMID:22228747

  10. Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate

    SciTech Connect

    Hildebrandt, P.; Birch, K.; Jensen, B.M.; Kuehl, C.

    1986-11-01

    Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of /sup 125/I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting.

  11. Implantable, remotely-programmable insulin infusion system

    SciTech Connect

    Carlson, G.A.; Bair, R.E.; Gaona, J.I. Jr.; Love, J.T.; Urenda, R.S.

    1981-10-01

    An implantable, remotely-programmable insulin infusion system is described which has a mass of 280 grams and an implanted lifetime exceeding two years. The system uses a rotary solenoid-driven peristaltic pump controlled by low power CMOS timing circuitry which provides bimodal insulin delivery. Fifteen low rates from 0.39 to 5.9 units/hour and 15 high doses from 0.84 to 12.5 units are available using U100 insulin. The system has been tested in the laboratory, evaluated in diabetic dogs, and implanted in one diabetic human.

  12. A Comparison Study of Continuous Insulin Infusion Protocols in the Medical Intensive Care Unit: Computer-Guided Vs. Standard Column-Based Algorithms

    PubMed Central

    Newton, Christopher A.; Smiley, Dawn; Bode, Bruce W.; Kitabchi, Abbas E.; Davidson, Paul C.; Jacobs, Sol; Steed, R. Dennis; Stentz, Frankie; Peng, Limin; Mulligan, Patrick; Freire, Amado X.; Temponi, Angel; Umpierrez, Guillermo E.

    2013-01-01

    PURPOSE To compare the safety and efficacy of continuous insulin infusion (CII) via a computer-guided and a standard paper form protocol in a medical intensive care unit (ICU). METHODS Multicenter randomized trial of 153 ICU patients randomized to CII using the Glucommander (n = 77) or a standard paper protocol (n = 76). Both protocols used glulisine insulin and targeted blood glucose (BG) between 80 mg/dL and 120 mg/dL. RESULTS The Glucommander resulted in a lower mean BG value (103 ± 8.8 mg/dL vs. 117 ± 16.5 mg/dL, P < 0.001) and in a shorter time to reach BG target (4.8 ± 2.8 vs.7.8 hours ± 9.1 hours, P < 0.01), and once at target resulted in a higher percentage of BG readings within target (71.0 ± 17.0% vs. 51.3 ± 19.7%, P < 0.001) than the standard protocol. Mean insulin infusion rate in the Glucommander was similar to the standard protocol (P = 0.12). The percentages of patients with ≥1 episode of BG <40 mg/dL and <60 mg/dL were 3.9% and 42.9% in the Glucommander and 5.6% and 31.9% in the standard, respectively [P = not significant (NS)]. Repeated measures analyses show that the probabilities of BG reading <40 mg/dL or <60 mg/dL were not significantly different between groups (P = 0.969, P = 0.084) after accounting for within-patient correlations with or without adjusting for time effect. There were no differences between groups in the length of hospital stay (P = 0.704), ICU stay (P = 0.145), or inhospital mortality (P = 0.561). CONCLUSION Both treatment algorithms resulted in significant improvement in glycemic control in critically ill patients in the medical ICU. The computer-based algorithm resulted in tighter glycemic control without an increased risk of hypoglycemic events compared to the standard paper protocol. PMID:20945468

  13. Comparison of the Effects of Continuous Subcutaneous Insulin Infusion and Add-On Therapy with Sitagliptin in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

    PubMed

    Wan, Heng; Zhao, Defu; Shen, Jie; Lu, Lu; Zhang, Tong; Chen, Zhi

    2016-01-01

    To identify a new regimen to optimize treatment for patients with newly diagnosed type 2 diabetes (T2DM) by short-term continuous subcutaneous insulin infusion (CSII) alone. Methods. 60 patients with newly diagnosed T2DM were randomized into two groups (n = 30 each) and treated for 2 weeks with CSII alone (CSII group) or with CSII plus sitagliptin (CSII + Sig group). The glycemic variability of the patients was measured using a continuous glucose monitoring system (CGMS) for the last 72 hours. A standard meal test was performed before and after the interventions, and the levels of glycated albumin, fasting glucose, fasting C-peptide, postprandial 2 h blood glucose, and postprandial 2 h C-peptide were examined. Results. Compared with the CSII group, the indicators of glycemic variability, such as the mean amplitude of glycemic excursion (MAGE) and the standard deviation of blood glucose (SDBG), were decreased significantly in the CSII + Sig group. The changes before and after treatment in the C-peptide reactivity index (ΔCPI) and the secretory unit of islet in transplantation index (ΔSUIT) indicated a significant improvement in the CSII + Sig group. Conclusions. Add-on therapy with sitagliptin may be an optimized treatment for patients with newly diagnosed T2DM compared with short-term CSII alone. PMID:26798658

  14. Cross-sectional Survey and Retrospective Analysis of a Large Cohort of Adults With Type 1 Diabetes With Long-Term Continuous Subcutaneous Insulin Infusion Treatment

    PubMed Central

    Morera, Julia; Vicente, Angel; Rod, Anne; Parienti, Jean-Jacques; Reznik, Yves

    2014-01-01

    Background. Continuous subcutaneous insulin infusion (CSII) is an established modality for intensive insulin treatment of type 1 diabetes (T1D), but long-term data concerning satisfaction, CSII function use, safety, and efficacy in real-life conditions are scarce. Methods. We analyzed a cohort of adult patients with T1D treated with CSII for more than 1 year in a single diabetes center. We performed a cross-sectional survey in 2010 (tolerance/satisfaction and behavior forms) and a retrospective analysis of medical records (including HbA1c level, hospitalization, and catheter infections). The primary objective was to assess long-term tolerance/satisfaction, and secondary objectives were safety and efficacy. Results. There were 295 patients analyzed. After a median duration of CSII use of 5 years, overall satisfaction was high for about 90% of patients. Mean CSII-related discomfort scores were low for work, recreation, and sleep and moderate for sport and sexual activity (2.5 ± 1.9, 2.6 ± 1.8, 2.6 ± 2.1, 3.4 ± 2.3, and 4.0 ± 2.9 of 10, respectively). Despite a high level of diabetes education, only one third of patients were using advanced CSII functions. During long-term follow-up, the safety of CSII treatment was good; the hospitalization rate was 0.18 patients/year, and catheter infections were scarce. The HbA1c level dropped about −0.5% independently from CSII duration (P < .05). Conclusions. In this adult cohort, satisfaction and tolerance, together with safety, of CSII were maintained at long-term follow up. The sole basic functions of CSII were currently used by patients. A 0.5% decrease in the HbA1c level was maintained during the study period. PMID:24876454

  15. [Continuous intravenous infusion of insulin to girls with hereditary tall growth and secretion of human growth hormone, prior to and during Deposiston treatment (author's transl)].

    PubMed

    Richter, J; Heine, W; Rudolf, K; Uhlmann, M

    1980-01-01

    Continuous intravenous insulin infusion tests, accompanied by growth hormone determination, were applied to 40 girls of tall growth whose final lengths were predicted to be in excess of 181 cm. The girls were aged between nine and half and 14 years and one month, all of them being in the premenarchic phase. The tests were conducted prior to and following at least one year of Deposiston therapy (oestrogen/gestagen). - Really effective inhibition of growth (7.4 +/- 0.6 cm) was obtained only from five girls, aged between nine years and ten months and eleven years, in whom basal secretion of HGH was lower with significance than that of the whole group, with their stimulation reaction being fully retained. Secretion of somatotropic hormone (STH) of the other girls remained unaffected, prior to and following treatment. The weekly oestrogen dose of 1 mg was relatively low, when compared to propositions made by other authors, but it seemed to be justified by the average reduction in expected final body length obtained for the probands reviewed (5.4 +/- 2.0 cm). PMID:7008461

  16. 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

  17. A Review of the Security of Insulin Pump Infusion Systems

    SciTech Connect

    Klonoff, David C.; Paul, Nathanael R; Kohno, Tadayoshi

    2011-01-01

    Insulin therapy has enabled diabetic patients to maintain blood glucose control to lead healthier lives. Today, rather than manually injecting insulin using syringes, a patient can use a device, such as an insulin pump, to programmatically deliver insulin. This allows for more granular insulin delivery while attaining blood glucose control. The insulin pump system features have increasingly benefited patients, but the complexity of the resulting system has grown in parallel. As a result security breaches that can negatively affect patient health are now possible. Rather than focus on the security of a single device, we concentrate on protecting the security of the entire system. In this paper we describe the security issues as they pertain to an insulin pump system that includes an embedded system of components including the insulin pump, continuous glucose management system, blood glucose monitor, and other associated devices (e.g., a mobile phone or personal computer). We detail not only the growing wireless communication threat in each system component, but we also describe additional threats to the system (e.g., availability and integrity). Our goal is to help create a trustworthy infusion pump system that will ultimately strengthen pump safety, and we describe mitigating solutions to address identified security issues both for now and in the future.

  18. 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

  19. Pharmacokinetics and toxicology of continuously infused nitroimidazoles

    SciTech Connect

    Eifel, P.J.; Brown, J.M.

    1984-08-01

    The pharmacokinetics and toxicology of misonidazole (MISO) and SR-2508 given by continuous intraperitoneal infusion were studied in female C/sub 3/H mice. The survival (time to death) of animals receiving continuous infusions of SR-2508 and MISO was compared and related to plasma concentration, rate of infusion and total amount of drug delivered. Brain and plasma concentrations were determined by HPLC. For SR-2508, plasma concentration was directly proportional to the infusion rate. However, as the infusion rate of MISO was doubled, the plasma concentration of MISO increased approximately 6-fold, reflecting a substantial increase in the apparent half-life. The brain/plasma concentration ratio in animals infused for up to 6 days with SR-2508 remained constant, at approximately 0.09. At plasma concentrations of 0.08-1.5 mM, animals receiving SR-2508 survived approximately 3 times as long as animals exposed to a comparable plasma concentration of MISO. Even at the lowest infusion rates employed in this study, the survival of mice receiving SR-2508 was much shorter than would have been predicted if the toxicity of these two drugs were solely related to the integral brain exposure. The low brain/plasma concentration ratio of SR-2508 was maintained throughout long continuous exposures.

  20. Effects of Liraglutide Combined with Short-Term Continuous Subcutaneous Insulin Infusion on Glycemic Control and Beta Cell Function in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Pilot Study

    PubMed Central

    Ke, Weijian; Liu, Liehua; Liu, Juan; Chen, Ailing; Deng, Wanping; Zhang, Pengyuan; Cao, Xiaopei; Liao, Zhihong; Xiao, Haipeng; Liu, Jianbin; Li, Yanbing

    2016-01-01

    The objective of this paper is to investigate the effects of liraglutide in combination with short-term continuous subcutaneous insulin infusion (CSII) therapy on glycemic control and beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM). Thirty-nine eligible newly diagnosed T2DM patients were recruited and randomized to receive either of two therapies: short-term CSII alone (CSII alone group) or CSII in combination with liraglutide (CSII + Lira group) for 12 weeks. Blood glucose control, homeostasis model assessment (HOMA) indices, and acute insulin response (AIR) were compared between the two groups. The patients in CSII + Lira group achieved euglycemia with equivalent insulin dosage in shorter time (1 (0) versus 2 (3) days, P = 0.039). HbA1c at the end of study was comparable between two groups (6.3 ± 0.7% versus 6.0 ± 0.5%, for CSII alone group and CSII + Lira group, resp., P = 0.325). The increment of AIR was higher in CSII + Lira group (177.58 (351.57) μU·min/mL versus 58.15 (51.30) μU·min/mL, P < 0.001). However, after stopping liraglutide, its effect on beta cell function disappeared completely. Liraglutide combined with short-term CSII was effective in further improving beta cell function, but the beneficial effects did not sustain after suspension of the therapy. PMID:26640805

  1. A Hazard Analysis for a Generic Insulin Infusion Pump

    PubMed Central

    Zhang, Yi; Jones, Paul L.; Jetley, Raoul

    2010-01-01

    Background Researchers at the Food and Drug Administration (FDA)/Center for Device and Radiological Health/Office of Science and Engineering Laboratories have been exploring the concept of model-based engineering as a means for improving the quality of medical device software. Insulin pumps were chosen as a research subject because their design provides the desired degree of research complexity and these types of devices present an ongoing regulatory challenge. Methods Insulin pump hazards and their contributing factors are considered in the context of a highly abstract generic insulin infusion pump (GIIP) model. Hazards were identified by consulting with manufacturers, pump users, and clinicians; by reviewing national and international standards and adverse event reports collected by the FDA; and from workshops sponsored by Diabetes Technology Society. This information has been consolidated in tabular form to facilitate further community analysis and discussion. Results A generic insulin infusion pump model architecture has been established. A fairly comprehensive hazard analysis document, corresponding to the GIIP model, is presented in this article. Conclusions We believe that this work represents the genesis of an insulin pump safety reference standard upon which future insulin pump designs can be based to help ensure a basic level of safety. More interaction with the diabetes community is needed to assure the quality of this safety modeling process. PMID:20307387

  2. Stimulation of muscle protein synthesis by long-term insulin infusion in severely burned patients.

    PubMed Central

    Sakurai, Y; Aarsland, A; Herndon, D N; Chinkes, D L; Pierre, E; Nguyen, T T; Patterson, B W; Wolfe, R R

    1995-01-01

    OBJECTIVE: To determine if long-term (7 days) infusion of insulin can ameliorate altered protein kinetics in skeletal muscle of severely burned patients and to investigate the hypothesis that changes in protein kinetics during insulin infusion are associated with an increased rate of transmembrane amino acid transport from plasma into the intracellular free amino acid pool. SUMMARY BACKGROUND DATA: In critically ill patients, vigorous nutritional support alone may often fail to entirely curtail muscle catabolism; insulin stimulates muscle protein synthesis in normal volunteers. METHODS: Nine patients with severe burns were studied once during enteral feeding alone (control period), and once after 7 days of high-dose insulin. The order of treatment with insulin was randomized. Data were derived from a model based on a primed-continuous infusion of L-[15N]phenylalanine, sampling of blood from the femoral artery and vein, and biopsies of the vastus lateralis muscle. RESULTS: Net leg muscle protein balance was significantly (p < 0.05) negative during the control period. Exogenous insulin eliminated this negative balance by stimulating protein synthesis approximately 350% (p < 0.01). This was made possible in part by a sixfold increase in the inward transport of amino acids from blood (p < 0.01). There was also a significant increase in leg muscle protein breakdown. The new rates of synthesis, breakdown, and inward transport during insulin were in balance, such that there was no difference in the intracellular phenylalanine concentration from the control period. The fractional synthetic rate of protein in the wound was also stimulated by insulin by approximately 50%, but the response was variable and did not reach significance. CONCLUSIONS: Exogenous insulin may be useful in promoting muscle protein synthesis in severely catabolic patients. PMID:7677459

  3. The direct cost of intravenous insulin infusions to the NHS in England and Wales.

    PubMed

    Rajendran, Rajesh; Scott, Anne; Rayman, Gerry

    2015-08-01

    The cost of intravenous insulin infusion to the NHS is unknown. The aim of this study was to estimate the direct cost of insulin infusions to the NHS in England and Wales in the first 24-hour period of infusion. Data from the National Inpatient Diabetes Audit 2013 in the UK were used to estimate the number of insulin infusions in use across England and Wales. Costs were calculated for six models for setting up and maintenance of insulin infusions, depending on the extent of involvement of different healthcare professionals in the UK. In this study, the direct costs of intravenous insulin infusions to the NHS in England and Wales have been estimated to vary from £6.4-8.5 million in the first 24-hour period on infusion. More appropriate use of these infusions could result in substantial cost savings. PMID:26407380

  4. Stability of thyroid hormones during continuous infusion.

    PubMed

    Golombek, Sergio G; Alpan, Gad; Frey, Michael; Corbi, Dominick; Lagamma, Edmund F

    2011-07-01

    We investigated the stability of thyroid hormones during a mode of continuous drug infusion via polypropylene tubing using the same conditions that would be applied to treating patients in a hospital setting. The diluted thyroid hormones were prepared using aseptic technique, stored at 2-8°C (36-46°F) and tested within 24 h of preparation for stability and percent recovery from within plastic tubing. Experiments were done in duplicate with triplicate sets of readings for each assay point. Only T(4) prepared with 5% dextrose water (D5W) containing 1 mg/mL albumin remained constant, stable, predictable and accurate over time under various conditions. Other methods of preparation lost drug by adhering to the plastic containers and tubing by as much as 40% of starting concentration. T(3) recovery in the presence of 1 mg/mL of albumin was 107±2% (mean±standard error of the mean) of anticipated drug concentrations. We conclude from this series of experiments that to maintain an accurate and stable dosing of patients receiving intravenous thyroid hormones, 1 mg/mL of albumin must be added to the infusate to prevent lost on the plastic intravenous tubing. PMID:21501101

  5. Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin.

    PubMed

    Morris, Jill K; Vidoni, Eric D; Mahnken, Jonathan D; Montgomery, Robert N; Johnson, David K; Thyfault, John P; Burns, Jeffrey M

    2016-03-01

    Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p < 0.0001) and no change in performance on an additional task (delayed logical memory). In this study, although insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND

  6. Insulin Infusion Set Use: European Perspectives and Recommendations.

    PubMed

    Deiss, Dorothee; Adolfsson, Peter; Alkemade-van Zomeren, Marije; Bolli, Geremia B; Charpentier, Guillaume; Cobelli, Claudio; Danne, Thomas; Girelli, Angela; Mueller, Heiko; Verderese, Carol A; Renard, Eric

    2016-09-01

    Insulin pump users worldwide depend on insulin infusion sets (IISs) for predictable delivery of insulin to the subcutaneous tissue. Yet emerging data indicates that IISs are associated with many pump-related adverse events and may contribute to potentially life-threatening problem of unexplained hyperglycemia. The relative scarcity of published research on IISs to date, the heterogeneity of regional IIS practices, and the increasing demand for international standards guiding their use prompted convening of a panel of diabetologists and diabetes nurse educators last February, in Milan, Italy, to discuss a framework for optimizing IIS practice in Europe. The multinational panel was tasked, first, with identifying the often-overlooked IIS issues that can affect patients' experience of pump therapy-e.g., partial or complete blockage of the cannula, skin pathologies, unpredictable variations in insulin absorption, dislodgment, and the demands of site rotation and set changes-and, second, with establishing direction for developing cohesive protocols to assure long-term success. As reported in this article, the panel examined IIS-related complications of pump therapy encountered in clinical practice, considered country-wide policies to prevent and mitigate such complications, and updated priorities for improving IIS education on issues of device selection, skin care, and troubleshooting unexplained hyperglycemia. These recommendations may be more relevant with the possibility of closed-loop systems available in the near future. PMID:27526329

  7. Comparative Dose Accuracy of Durable and Patch Insulin Infusion Pumps

    PubMed Central

    Jahn, Luis G.; Capurro, Jorge J.; Levy, Brian L.

    2013-01-01

    Background: As all major insulin pump manufacturers comply with the international infusion pump standard EN 60601-2-24:1998, there may be a general assumption that all pumps are equal in insulin-delivery accuracy. This research investigates single-dose and averaged-dose accuracy of incremental basal deliveries for one patch model and three durable models of insulin pumps. Method: For each pump model, discrete single doses delivered during 0.5 U/h basal rate infusion over a 20 h period were measured using a time-stamped microgravimetric system. Dose accuracy was analyzed by comparing single doses and time-averaged doses to specific accuracy thresholds (±5% to ±30%). Results: The percentage of single doses delivered outside accuracy thresholds of ±5%, ±10%, and ±20% were as follows: Animas OneTouch® Ping® (43.2%, 14.3%, and 1.8%, respectively), Roche Accu-Chek® Combo (50.6%, 24.4%, and 5.5%), Medtronic Paradigm® RevelTM/VeoTM (54.2%, 26.7%, and 6.6%), and Insulet OmniPod® (79.1%, 60.5%, and 34.9%). For 30 min, 1 h, and 2 h averaging windows, the percentage of doses delivered outside a ±15% accuracy were as follows: OneTouch Ping (1.0%, 0.4%, and 0%, respectively), Accu-Chek Combo (4.2%, 3.5%, and 3.1%), Paradigm Revel/Veo (3.9%, 3.1%, and 2.2%), and OmniPod (33.9%, 19.9%, and 10.3%). Conclusions: This technical evaluation demonstrates significant differences in single-dose and averaged-dose accuracy among the insulin pumps tested. Differences in dose accuracy were most evident between the patch pump model and the group of durable pump models. Of the pumps studied, the Animas OneTouch Ping demonstrated the best single-dose and averaged-dose accuracy. Further research on the clinical relevance of these findings is warranted. PMID:23911184

  8. Changes in fetal mannose and other carbohydrates induced by a maternal insulin infusion in pregnant sheep

    PubMed Central

    2014-01-01

    Background The importance of non-glucose carbohydrates, especially mannose and inositol, for normal development is increasingly recognized. Whether pregnancies complicated by abnormal glucose transfer to the fetus also affect the regulation of non-glucose carbohydrates is unknown. In pregnant sheep, maternal insulin infusions were used to reduce glucose supply to the fetus for both short (2-wk) and long (8-wk) durations to test the hypothesis that a maternal insulin infusion would suppress fetal mannose and inositol concentrations. We also used direct fetal insulin infusions (1-wk hyperinsulinemic-isoglycemic clamp) to determine the relative importance of fetal glucose and insulin for regulating non-glucose carbohydrates. Results A maternal insulin infusion resulted in lower maternal (50%, P < 0.01) and fetal (35-45%, P < 0.01) mannose concentrations, which were highly correlated (r2 = 0.69, P < 0.01). A fetal insulin infusion resulted in a 50% reduction of fetal mannose (P < 0.05). Neither maternal nor fetal plasma inositol changed with exogenous insulin infusions. Additionally, maternal insulin infusion resulted in lower fetal sorbitol and fructose (P < 0.01). Conclusions Chronically decreased glucose supply to the fetus as well as fetal hyperinsulinemia both reduce fetal non-glucose carbohydrates. Given the role of these carbohydrates in protein glycosylation and lipid production, more research on their metabolism in pregnancies complicated by abnormal glucose metabolism is clearly warranted. PMID:24917928

  9. Radiofrequency ablation during continuous saline infusion can extend ablation margins

    PubMed Central

    Ishikawa, Toru; Kubota, Tomoyuki; Horigome, Ryoko; Kimura, Naruhiro; Honda, Hiroki; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki

    2013-01-01

    AIM: To determine whether fluid injection during radiofrequency ablation (RFA) can increase the coagulation area. METHODS: Bovine liver (1-2 kg) was placed on an aluminum tray with a return electrode affixed to the base, and the liver was punctured by an expandable electrode. During RFA, 5% glucose; 50% glucose; or saline fluid was infused continuously at a rate of 1.0 mL/min through the infusion line connected to the infusion port. The area and volume of the thermocoagulated region of bovine liver were determined after RFA. The Joule heat generated was determined from the temporal change in output during the RFA experiment. RESULTS: No liquid infusion was 17.3 ± 1.6 mL, similar to the volume of a 3-cm diameter sphere (14.1 mL). Mean thermocoagulated volume was significantly larger with continuous infusion of saline (29.3 ± 3.3 mL) than with 5% glucose (21.4 ± 2.2 mL), 50% glucose (16.5 ± 0.9 mL) or no liquid infusion (17.3 ± 1.6 mL). The ablated volume for RFA with saline was approximately 1.7-times greater than for RFA with no liquid infusion, representing a significant difference between these two conditions. Total Joule heat generated during RFA was highest with saline, and lowest with 50% glucose. CONCLUSION: RFA with continuous saline infusion achieves a large ablation zone, and may help inhibit local recurrence by obtaining sufficient ablation margins. RFA during continuous saline infusion can extend ablation margins, and may be prevent local recurrence. PMID:23483097

  10. Effect of insulin and glucose infusion on myocardial infarction size in uraemic rats.

    PubMed

    Dikow, Ralf; Wasserhess, Caroline; Zimmerer, Katrin; Kihm, Lars Philipp; Schaier, Matthias; Schwenger, Vedat; Hardt, Stefan; Tiefenbacher, Christiane; Katus, Hugo; Zeier, Martin; Gross, Lisa Marie

    2009-09-01

    The post myocardial infarction (MI) mortality rate is high in renal patients. One possible explanation is the reduced ischemia tolerance caused by uraemia. Previous investigations showed larger MI size in uraemic rats when compared with sham-operated controls. To explore a possible link between uraemic insulin resistance syndrome and MI size in uraemia, we studied an intervention model with administration of insulin and glucose during acute MI in subtotally nephrectomized (SNX) rats and sham-operated controls. In 16 SNX rats and 16 sham-operated controls, the left coronary artery was ligated for 60 min, followed by reperfusion for 90 min. To visualize the perfused myocardium, lissamine-green ink was injected. The nonperfused area (lissamine exclusion) and the area of total infarction (TTC stain) were assessed in sections of the left ventricle (LV) using image analysis. While eight SNX rats and eight sham-operated controls were treated with a placebo during the procedure, the other animals received an insulin bolus of 85 mU/kg and then a continuous insulin infusion of 8 mU/kg per minute. Blood glucose levels were clamped to baseline levels with an infusion of 25% glucose. Insulin receptor substrates (IRS-1 and IRS-2) and glucose transporter (GLUT 4) were studied by western blot in another seven SNX and seven sham-operated controls without further intervention. The infarcted area, given as a proportion of the nonperfused risk area, was not different in sham-operated controls treated with a hyperinsulinaemic clamp versus untreated (0.55 +/- 0.07 vs. 0.51 +/- 0.13, p = 0.477). The eight SNX animals treated with the hyperinsulinaemic clamp utilized significantly less glucose to stabilize baseline glucose levels when compared with the sham-operated controls (5,637 vs. 3,207 microl Glc 25%, p = 0.007). The infarcted area was significantly lower in SNX rats treated with the hyperinsulinaemic clamp compared to non-treated SNX animals (0.56 +/- 0.06 vs. 0.79 +/- 0.09, p < 0

  11. Responses of Blood Glucose, Insulin, Glucagon, and Fatty Acids to Intraruminal Infusion of Propionate in Hanwoo

    PubMed Central

    Oh, Y. K.; Eun, J. S.; Lee, S. C.; Chu, G. M.; Lee, Sung S.; Moon, Y. H.

    2015-01-01

    This study was carried out to investigate the effects of intraruminal infusion of propionate on ruminal fermentation characteristics and blood hormones and metabolites in Hanwoo (Korean cattle) steers. Four Hanwoo steers (average body wt. 270 kg, 13 month of age) equipped with rumen cannula were infused into rumens with 0.0 M (Water, C), 0.5 M (37 g/L, T1), 1.0 M (74 g/L, T2) and 1.5 M (111 g/L, T3) of propionate for 1 hour per day and allotted by 4×4 Latin square design. On the 5th day of infusion, samples of rumen and blood were collected at 0, 60, 120, 180, and 300 min after intraruminal infusion of propionate. The concentrations of serum glucose and plasma glucagon were not affected (p>0.05) by intraruminal infusion of propionate. The serum insulin concentration at 60 min after infusion was significantly (p<0.05) higher in T3 than in C, while the concentration of non-esterified fatty acid (NEFA) at 60 and 180 min after infusion was significantly (p<0.05) lower in the propionate treatments than in C. Hence, intraruminal infusion of propionate stimulates the secretion of insulin, and decreases serum NEFA concentration rather than the change of serum glucose concentration. PMID:25557815

  12. A guideline for the use of variable rate intravenous insulin infusion in medical inpatients.

    PubMed

    George, S; Dale, J; Stanisstreet, D

    2015-06-01

    The present paper summarizes the key recommendations in a recent publication produced by the Joint British Diabetes Societies for Inpatient Care on the use of variable rate i.v. insulin infusion in 'medical' inpatients. The full guideline is available at http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_VRIII.pdf and is designed to be a practical guide that can used by any healthcare professional who manages medical inpatients with hyperglycaemia. Its main aim is to allow variable rate i.v. insulin infusion to be used safely, effectively and efficiently for this specific group of inpatients. PMID:25980646

  13. Experience with intraperitoneal insulin infusion from implantable programmable systems in type 1 (insulin-dependent) diabetes mellitus previously treated by external pumps.

    PubMed

    Renard, E; Lauton, D; Bonifacj, C; Costalat, G; Jacques, D; Bringer, J; Jaffiol, C

    1993-01-01

    The feasibility of the continuous intraperitoneal insulin infusion from implantable programmable systems was evaluated in 17 Type 1 (insulin-dependent) diabetic patients currently treated by external pumps. Eight subjects were using a continuous subcutaneous insulin infusion (cumulated experience: 7.4 patients x years) and nine subjects had a cumulated experience of 61.4 patients x years of continuous intra peritoneal insulin delivery by external pumps. The two studied implantable systems (A and B) were delivering the same pH neutral surfactant-stabilized semi-synthetic human insulin, but at the respective concentrations of 400 units per ml in group A (n = 12) and of 100 units per ml in group B (n = 5), via a peritoneal catheter. The pump was implanted in a subcutaneous pocket created in the abdominal wall under general anesthesia. The reported trial of implantable programmable systems is 21 patient x years with an individual experience of 1.2 +/- 0.4 years (mean +/- SD). A sustained and stable glycaemic control was obtained, as indicated by the haemoglobin A1c: 7.4 +/- 1.3% (normal range: 4.3-6.1%), the mean blood glucose: 7.4 +/- 2.1 mM.l-1, the standard deviation of blood glucose values: 3.4 +/- 0.4 mM.l-1 and the percentages of 13.1 +/- 4.5% and 6.1 +/- 6.1% of blood glucose values respectively over 11 mM.l-1 and under 2.8 mM.l-1 after one year. The only metabolic event to occur was one episode of ketoacidosis secondary to a catheter obstruction. No hypoglycaemic coma occurred contrasting with incidences of 0.54 and 0.05 per patient x year during subcutaneous external and intraperitoneal pumps respectively (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8293863

  14. The effect of portal infusions of epinephrine on ingestion, plasma glucose and insulin in dogs.

    PubMed

    Bellinger, L L; Williams, F E

    1990-09-01

    Preabsorptive satiety has been hypothesized to occur as the result of food activating oral and gastrointestinal receptors that cause the release of catecholamines in the liver. The catecholamines were then proposed to hyperpolarize hepatic glucoreceptors and produce satiety. In the present study the hepatic portal vein was chronically cannulated in six mongrel dogs. Upon recovery the dogs were infused, over three minutes, with either saline or epinephrine (0.83 and 1.5 micrograms/kg b. wt.). Infusions ended 10 minutes prior to the animals' daily one-hour feeding period. The epinephrine infusions resulted in physiological increases in plasma glucose and insulin, but did not inhibit food consumption. The animals were next prefed 20% of their normal daily food intake 30 minutes prior to infusion of epinephrine at the above noted doses. Again plasma glucose and insulin increased, but food consumption was not affected. These data show that epinephrine infusions which produce physiological changes in plasma glucose and insulin do not alter feeding behavior of mongrel dogs. These findings are in agreement with previous data that question the physiological importance of the preabsorptive catecholamine satiety hypothesis. PMID:2176295

  15. The regulatory system for diabetes mellitus: Modeling rates of glucose infusions and insulin injections

    NASA Astrophysics Data System (ADS)

    Yang, Jin; Tang, Sanyi; Cheke, Robert A.

    2016-08-01

    Novel mathematical models with open and closed-loop control for type 1 or type 2 diabetes mellitus were developed to improve understanding of the glucose-insulin regulatory system. A hybrid impulsive glucose-insulin model with different frequencies of glucose infusions and insulin injections was analyzed, and the existence and uniqueness of the positive periodic solution for type 1 diabetes, which is globally asymptotically stable, was studied analytically. Moreover, permanence of the system for type 2 diabetes was demonstrated which showed that the glucose concentration level is uniformly bounded above and below. To investigate how to prevent hyperinsulinemia and hyperglycemia being caused by this system, we developed a model involving periodic intakes of glucose with insulin injections applied only when the blood glucose level reached a given critical glucose threshold. In addition, our numerical analysis revealed that the period, the frequency and the dose of glucose infusions and insulin injections are crucial for insulin therapies, and the results provide clinical strategies for insulin-administration practices.

  16. Regional blood flow during continuous low-dose endotoxin infusion

    SciTech Connect

    Fish, R.E.; Lang, C.H.; Spitzer, J.A.

    1986-01-01

    Escherichia coli endotoxin (ET) was administered to adult rats by continuous IV infusion from a subcutaneously implanted osmotic pump (Alzet). Cardiac output and regional blood flow were determined by the radiolabeled microsphere method after 6 and 30 hr of ET or saline infusion. Cardiac output (CO) of ET rats was not different from time-matched controls, whereas arterial pressure was 13% lower after 30 hr of infusion. After both 6 and 30 hr of ET, pancreatic blood flow and percentage of cardiac output were lower than in controls. Estimated portal venous flow was decreased at each time point, and an increased hepatic arterial flow (significant after 30 hr) resulted in an unchanged total hepatic blood flow. Blood flow to most other tissues, including epididymal fat, muscle, kidneys, adrenals, and gastrointestinal tract, was similar between treatments. Maintenance of blood flow to metabolically important tissues indicates that the previously reported alterations in in vitro cellular metabolism are not due to tissue hypoperfusion. Earlier observations of in vitro myocardial dysfunction, coexistent with the significant impairment in pancreatic flow, raise the possibility that release of a myocardial depressant factor occurs not only in profound shock but also under less severe conditions of sepsis and endotoxemia.

  17. Intravenous infusion of glucose and insulin in relation to milk secretion in the sow.

    PubMed

    Reynolds, L; Rook, J A

    1977-01-01

    1. A comparison was made of the composition of milk from front and rear tetas in four sows. There were small and not significant differences in fat, protein and lactose contents, and in the fatty-acid composition of the milk fat with the exception of the 18:3 acid where the difference was also small but significant. 2. The effects of intravenous infusions of glucose and insulin in lactating sows on milk secretion and blood composition were investigated in two sows. 3. Intravenous infusion of glucose had no effect on blood plasma glucose concentration but increased the yields of lactose, protein and water. 4. Intravenous infusion of insulin depressed plasma glucose concentration and the yields of lactose and water. The yield of protein was unaffected. 5. It is concluded that differences between the non-ruminant (the sow) and the ruminant in the responses in milk secretion to glucose infusion may be related to differences in the sensitivity to insulin of mammary tissue. PMID:849401

  18. Minimization of Hypoglycemia as an Adverse Event During Insulin Infusion: Further Refinement of the Yale Protocol

    PubMed Central

    Inzucchi, Silvio E.; Besterman, Brian J.

    2016-01-01

    Abstract Background: The management of hyperglycemia in the intensive care unit has been a controversial topic for more than a decade, with target ranges varying from 80–110 mg/dL to <200 mg/dL. Multiple insulin infusion protocols exist, including several computerized protocols, which have attempted to achieve these targets. Importantly, compliance with these protocols has not been a focus of clinical studies. Methods: GlucoCare™, a Food and Drug Administration (FDA)-cleared insulin-dosing calculator, was originally designed based on the Yale Insulin Infusion Protocol to target 100–140 mg/dL and has undergone several modifications to reduce hypoglycemia. The original Yale protocol was modified from 100–140 mg/dL to a range of 120–140 mg/dL (GlucoCare 120–140) and then to 140 mg/dL (GlucoCare 140, not a range but a single blood glucose [BG] level target) in an iterative and evidence-based manner to eliminate hypoglycemia <70 mg/dL. The final modification [GlucoCare 140(B)] includes the addition of bolus insulin “midprotocol” during an insulin infusion to reduce peak insulin rates for insulin-resistant patients. This study examined the results of these protocol modifications and evaluated the role of compliance with the protocol in the incidence of hypoglycemia <70 mg/dL. Results: Protocol modifications resulted in mean BG levels of 133.4, 136.4, 143.8, and 146.4 mg/dL and hypoglycemic BG readings <70 mg/dL of 0.998%, 0.367%, 0.256%, and 0.04% for the 100–140, 120–140, 140, and 140(B) protocols, respectively (P < 0.001). Adherence to the glucose check interval significantly reduced the incidence of hypoglycemia (P < 0.001). Protocol modifications led to a reduction in peak insulin infusion rates (P < 0.001) and the need for dextrose-containing boluses (P < 0.001). Conclusion: This study demonstrates that refinements in protocol design can improve glucose control in critically ill patients and that the use of

  19. Sclerosing cholangitis after continuous hepatic artery infusion of FUDR.

    PubMed Central

    Kemeny, M M; Battifora, H; Blayney, D W; Cecchi, G; Goldberg, D A; Leong, L A; Margolin, K A; Terz, J J

    1985-01-01

    Eight of 46 (17.4%) patients treated in our trial of continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUDR) by Infusaid pump developed biliary strictures. The lesions were clinically, radiographically, and pathologically identical to the idiopathic sclerosing cholangitis frequently seen in association with inflammatory bowel disease. Treatment included immediate cessation of intraarterial FUDR, and surgical or percutaneous drainage of the biliary tree if it was dilated. Two of the eight patients died of the complication. Three patients stabilized after biliary system drainage, and two patients improved on observation only. The pathogenesis of this complication is not understood. This report details the clinical and pathological features of this entity. Images FIG. 1. FIG. 2. FIG. 3. FIG. 4. FIG. 5. FIG. 6. FIG. 7. PMID:3160313

  20. Euglycemic Infusion of Insulin Detemir Compared With Human Insulin Appears to Increase Direct Current Brain Potential Response and Reduces Food Intake While Inducing Similar Systemic Effects

    PubMed Central

    Hallschmid, Manfred; Jauch-Chara, Kamila; Korn, Oliver; Mölle, Matthias; Rasch, Björn; Born, Jan; Schultes, Bernd; Kern, Werner

    2010-01-01

    OBJECTIVE In the treatment of diabetic patients, the long-acting insulin analog insulin detemir is less prone to induce weight gain than other insulin formulations. Assuming that because of its pharmacologic properties, detemir displays stronger central nervous anorexigenic efficacy than human insulin, we compared acute effects of human insulin and detemir on electroencephalography (EEG) measures and food intake. RESEARCH DESIGN AND METHODS Frontocortical EEG direct current (DC) potentials were recorded in 15 healthy men during two hyperinsulinemic-euglycemic clamps that included an insulin bolus injection (human insulin, 17.75 mU/kg body wt; detemir, 90 mU/kg body wt) followed by a steady 90-min infusion (1.0 vs. 2.0 mU · kg−1 · min−1). A higher dosage was chosen for detemir to compensate for its delay in impact relative to human insulin and to elicit similar systemic effects. At 20 min after infusion, subjects were allowed to eat ad libitum from a test buffet. RESULTS Mean glucose infusions to maintain euglycemia (P > 0.93) and blood glucose concentrations (P > 0.34) did not differ between conditions. Detemir infusion induced a negative DC-potential shift, averaging −372.2 μV from 21 to 90 min that was not observed during human insulin infusion (146.5 μV, P = 0.02). Detemir, in comparison with human insulin, reduced subsequent food intake by 303 kcal (1,257 vs. 1,560, P < 0.04). CONCLUSIONS While inducing comparable peripheral effects, detemir exerts stronger acute effects on brain functions than human insulin and triggers a relative decrease in food consumption, suggesting an enhanced anorexigenic impact of detemir compared with human insulin on central nervous networks that control nutrient uptake. PMID:20068139

  1. 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

  2. Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

    PubMed

    Viscarra, Jose A; Rodriguez, Ruben; Vazquez-Medina, Jose Pablo; Lee, Andrew; Tift, Michael S; Tavoni, Stephen K; Crocker, Daniel E; Ortiz, Rudy M

    2013-08-01

    Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation. PMID:23997935

  3. Continuous infusion interleukin-2 and intravenous famotidine in metastatic melanoma.

    PubMed

    Quan, Walter D Y; Milligan, Karen S; Quan, Francine M; Cuenca, Rosa E; Khan, Nawazish; Liles, Darla K; Walker, Paul R

    2006-12-01

    Lymphokine-activated killer cell (LAK) cytotoxicity against tumor cells is induced by the use of high-dose infusional interleukin-2 (IL-2). LAK cytotoxicity against neoplastic cells may be augmented by famotidine. Twelve (12) patients have been treated with continuous infusion IL-2 (18 MIU/m2/24 hours) for 72 hours and famotidine 20 mg IVPB twice per day. Cycles were repeated every 3 weeks. These patients were of median age--67 years (range, 25-79), had a median performance status of 1 (range, 0-1), and had metastatic sites, including lung, lymph node, subcutaneous/soft tissue, and liver. The most common toxicities of this regimen were fever, rigors, nausea/emesis, hypophosphatemia, and hypomagnesemia. Three (3) partial responses have been seen (25% response rate). One (1) of these responders has undergone complete surgical resection and is disease-free at 15+ months. Four (4) patients are alive at a median of > 25 months. The median survival for all patients is 13 months. This combination of infusional IL-2 with famotidine is active in metastatic melanoma. PMID:17257076

  4. Continuous infusion interleukin-2 and antihistamines in metastatic kidney cancer.

    PubMed

    Walker, Paul R; Khuder, Sadik A; Quan, Walter D Y

    2005-10-01

    A prior randomized trial suggested a possible survival advantage favoring the combination of histamine and subcutaneous interleukin-2 (IL-2), compared to IL-2 alone in patients with metastatic melanoma. It has been postulated previously that antihistamines may, therefore, actually be antagonistic to IL-2 and thus interfere with its antitumor activity. We have previously shown no such antagonistic effect in patients with melanoma receiving IL-2 and antihistamines when reviewing the known literature. We sought to determine whether there was any negative effect of the combination in patients with metastatic kidney cancer. A PubMed literature search between 1985 and 2005 was done. High-dose continuous (or constant) infusion (CIV) interleukin-2 was used as the reference therapy because of the relatively constant IL-2 levels generated by this approach. Studies in which cimetidine, ranitidine, or famotidine were regularly scheduled and administered concurrently with IL-2 were included. Thirteen studies were identified. A total of 47 patients responded to therapy. Total response rate = 22%; 95%; Confidence Interval: 17%-28%. Eleven complete responses were noted. Complete response rate = 5%; 95% Confidence Interval: 3%-9%. These response rates are consistent with previously noted IL-2 response rates. In this study of CIV IL-2 and antihistamines, this combination appears to be active in metastatic kidney cancer. There appears to be no negative effect of antihistamine on the CIV IL-2 response rate in this disease. PMID:16248764

  5. Continuous infusion interleukin-2 and famotidine in metastatic kidney cancer.

    PubMed

    Quan, Walter D Y; Vinogradov, Mikhail; Quan, Francine M; Khan, Nawazish; Liles, Darla K; Walker, Paul R

    2006-10-01

    Infusional interleukin-2 (IL-2) is able to elicit lymphokine-activated killer cell (LAK) cytotoxicity against kidney cancer in vitro and in vivo. Famotidine may be able to augment LAK cytotoxicity against neoplastic cells. Fifteen (15) patients were treated with continuous-infusion IL-2 (9-18 MIU/m2/24 hours) for 72 hours and famotidine 20 mg intravenously twice per day. Cycles were repeated every 3 weeks. These patients had a median age of 60 years (range, 29-72), had a median performance status of 1 (range, 0-1), and had metastatic sites, including lung, bone, lymph node, and liver. The most common toxicities of this regimen were hypophosphatemia, fever, nausea/emesis, rigors, elevated creatinine, and hypomagnesemia. One (1) complete and 6 partial responses have been seen (47% response rate). The median duration of response is 9 months. The median survival for all patients is 20 months. Five (5) patients are alive at a median of 36+ months. This combination of infusional IL-2 with famotidine is active in metastatic kidney cancer. PMID:17105423

  6. Variable Patterns of Continuous Morphine Infusions at End of Life

    PubMed Central

    Lin, Katrina J.; Ching, Andrea; Edmonds, Kyle P.; Roeland, Eric J.; Revta, Carolyn; Ma, Joseph D.

    2015-01-01

    Abstract Background: Continuous morphine infusions (CMIs) treat pain and dyspnea at the end of life (EOL). CMIs may be initiated at an empiric rate and/or are rapidly escalated without proper titration. Objective: The study objective was to evaluate CMI patterns at the EOL. Methods: This single-center, retrospective chart review evaluated adult patients who died while receiving CMI at EOL. Patient demographics and opioid dosing information were extracted from an electronic medical record. Twenty-four hour IV morphine equivalent was calculated prior to CMI initiation and at the time of death. Results: Of the 190 patient charts, 63.2% (n=120) received no bolus doses prior to CMI initiation. Mean 24-hour IV morphine equivalent prior to CMI initiation was 49.3 mg (range: 0–1200 mg, SD 384.9) and at time of death was 267.1 mg (12.0–5193.2 mg, SD 442.2), representing an increase of +442%. Mean CMI starting rate was 3.3 mg/hour (0.4–30.0 mg/hour, SD 3.6) with titration at time of death to a mean of 7.7 mg/hour (0.4–70.0 mg/hour, SD 9.4), representing an increase of +130%. Mean number of CMI rate adjustments was 2.5 (0–5, SD 3.3); and number of bolus doses administered between titrations was 4.2 (0–27, SD 4.8). Mean time from CMI initiation to death was 15.5 hours (0.05–126.9 hours, SD 21.7). There was a negative association between rate of infusion increase per hour and total number of hours on CMI (r=−0.2, p=0.0062). Conclusions: Hospitalized patients at EOL had a much higher 24-hour IV morphine equivalents and CMI rates at time of death compared to CMI initiation. Variability was observed in the number of CMI rate adjustments and the number of bolus doses administered. PMID:26107143

  7. Improved myocardial contractility with glucose-insulin-potassium infusion during pacing in coronary artery disease.

    PubMed

    McDaniel, H G; Rogers, W J; Russell, R O; Rackley, C E

    1985-04-01

    The metabolic and mechanical effects of a solution of glucose-insulin-potassium (G-I-K) were investigated in 18 patients who underwent diagnostic cardiac catheterization for coronary artery disease. All patients were paced at a rate of approximately 140 beats/min before and after infusion of G-I-K. Basal and paced left ventricular (LV) end-diastolic pressure, dP/dt, arterial substrate levels and osmolarity were measured in all 18 patients. In 13 patients cardiac index was also measured. In 5 patients arterial-coronary sinus measurements of oxygen, carbon dioxide, glucose, free fatty acids, lactate, alanine, glutamate, glutamine, ammonia and urea were made, in addition to coronary sinus blood flow. G-I-K increased the blood sugar level to approximately 200 mg/dl and raised the serum osmolarity 9 mosmol. Pacing alone raised the cardiac index 4% and pacing with G-I-K increased the cardiac index 6% (p less than 0.05). Pacing before G-I-K augmented dP/dt (21%) and pacing with G-I-K increased it (30%) (p less than 0.01). The metabolic changes noted included a shift in the respiratory quotient from 0.77 to 0.96 with G-I-K infusion (p less than 0.05). During G-I-K infusion the myocardial oxygen consumption at rest increased from 17.1 to 21.8 ml/min (23%, p less than 0.05). Myocardial oxygen consumption during pacing was similar before and after G-I-K infusion. Before G-I-K infusion nitrogen balance was slightly positive; after G-I-K infusion it was negative with regard to the nitrogen-containing compounds measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3885708

  8. Effect of insulin with concurrent amino acid infusion on protein metabolism in rapidly growing pubertal children with type 1 diabetes.

    PubMed

    Godil, Mushtaq A; Wilson, Thomas A; Garlick, Peter J; McNurlan, Margaret A

    2005-08-01

    Insulin treatment of prepubertal children with insulin-dependent diabetes improves body protein balance by decreasing the rate of protein degradation without stimulating protein synthesis. However, insulin also causes hypoaminoacidemia, so the inability of insulin to stimulate protein synthesis may have been limited by substrate availability. We investigated the ability of insulin to stimulate protein synthesis in growing pubertal children who were given sufficient amino acids to counter insulin-induced hypoaminoacidemia. Protein metabolism in six pubertal children with type 1 diabetes was assessed from leucine kinetics during a primed, 6-h infusion of L-[1-(13)C]leucine. The children were studied in the postabsorptive state during a basal (insulin withdrawn) period and during the infusion of 0.83 mU * kg(-1) * min(-1) human regular insulin. Amino acids and glucose were given with insulin to prevent hypoaminoacidemia and hypoglycemia. Net leucine balance was significantly higher with insulin than in the basal state, the result of decreased protein degradation but also decreased protein synthesis. The data suggest that insulin alone does not increase protein synthesis in pubertal children with type 1 diabetes. PMID:16006430

  9. Cyclic AMP infusion and blood sugar, serum insulin and serum nonesterified fatty acid responses to glucose in recent experimental hyperthyroid dogs.

    PubMed

    Renauld, A; Garrido, D

    1992-01-01

    Recent experimental hyperthyroid (REH) dogs exhibit poor "in vivo" insulin responses to glucose probably due to a failure somewhere in cAMP-adenylate cyclase system. The actions of exogenous cAMP on these responses and on the regulation of blood sugar (BS) and serum nonesterified fatty acids (NEFA) during glucose infusion tests (GIT) in REH and normal dogs were studied here. Hyperthyroidism was induced by 1-thyroxine administration (100 micrograms/kg body wt./die, 10 days). GIT consisted of i.v. glucose-priming followed by glucose i.v. continuous infusion (60 min). cAMP (0, 33 or 66 mg/kg body wt./min) was infused alone (30 min) and then overlapped to gluco-se infusion (60 min). Peripheral veins were used for infusions and blood sample withdrawal. BS, serum inmunoreactive insulin (IRI) and serum NEFA concentrations, basally and throughout the test, were measured. Basally, there was neither action nor interaction of hyperthyroidism and exogenous cAMP on these variables. During the GIT, the BS levels remained unaffected by hyperthyroidism; cAMP increased them, but failed to interact with hyperthyroidism. cAMP noninfused normal dogs responded to hyperglycemia with hyperinsulinemia, whereas REH dogs noninfused the nucleotide did not. cAMP administration at a high dose promoted their response in normal and REH dogs, particularly in the former; in the latter, the response was still lower than in cAMP noninfused normal controls. Although recent hyperthyroidism increased serum NEFA basal level, it exerted neither action nor interaction with the infused cAMP on serum NEFA during GIT. Results are discussed on the basis that the abolished insulin secretion "in vivo" characterizing the REH dogs, related to beta-adrenergic deficiency, can be for the most part restored by exogenous cAMP administration, despite which some glucose and triglyceride metabolism impairments are developed. PMID:1343982

  10. Two case reports of retained steel insulin pump infusion set needles.

    PubMed

    Plager, Phillip; Murati, Michael A; Moran, Antoinette; Sunni, Muna

    2016-03-01

    Insulin pumps are common in the management of type 1 diabetes (T1D). We report two cases of metal insulin infusion set needles which broke off the tubing and remained embedded in the soft tissue of two boys with T1D (five needles in one case, and one needle in the other). The patient with five retained needles was asymptomatic and had a normal physical examination, and the missing needles were only detected using pelvic X-ray; the second patient had only mild discomfort. While these are the first such cases reported in the medical literature, there may be other cases which have gone unnoticed, suggesting the potential need to explore the safety of this product further. PMID:25683199

  11. Serum concentrations of amoxicillin in neonates during continuous intravenous infusion.

    PubMed

    van Boekholt, A; Fleuren, H; Mouton, J; Kramers, C; Sprong, T; Gerrits, P; Semmekrot, B

    2016-06-01

    Amoxicillin is commonly used for the treatment of neonatal bacterial infection with intermittent dosing (ID) regimens. However, increasing bacterial resistance, in addition to a lack of new antimicrobial agents, urges the optimization of current therapeutic options. Clinical studies in adults suggest continuous infusion (CI) regimens of beta-lactam antibiotics to be superior to ID. There are as yet no guidelines concerning the CI dosing of amoxicillin. The present study was developed to describe the CI pharmacokinetics and -dynamics of amoxicillin during the first 3 days of life in search of the optimal dosing regimen. Neonates with a gestational age above 34 weeks, at risk of neonatal infection and requiring amoxicillin therapy, were included. Serum concentrations of amoxicillin were measured during CI on days 1 and 3 in the steady state. Twenty-two serum samples of 11 patients were collected. All patients reached and retained serum concentrations of amoxicillin within the therapeutic range without exceeding the toxic concentration (serum concentrations on day 1 mean 55.4 mg/l, range 30.9-69.5, SD 10.5, and on day 3 48.8 mg/l, range 25.5-92.4, SD 18.4). There was no significant decrease in concentration from day 1 to day 3 (p = 0.38). This study showed therapeutic, nontoxic concentrations of amoxicillin in neonates on CI of amoxicillin in the first 3 days of life. Randomized controlled trials should reveal whether the clinical benefits of the CI of amoxicillin exceed those of ID regimens. PMID:27039340

  12. Chronic central leptin infusion modulates the glycemia response to insulin administration in male rats through regulation of hepatic glucose metabolism.

    PubMed

    Burgos-Ramos, Emma; Canelles, Sandra; Rodríguez, Amaia; Gómez-Ambrosi, Javier; Frago, Laura M; Chowen, Julie A; Frühbeck, Gema; Argente, Jesús; Barrios, Vicente

    2015-11-01

    Leptin and insulin use overlapping signaling mechanisms to modify hepatic glucose metabolism, which is critical in maintaining normal glycemia. We examined the effect of an increase in central leptin and insulin on hepatic glucose metabolism and its influence on serum glucose levels. Chronic leptin infusion increased serum leptin and reduced hepatic SH-phosphotyrosine phosphatase 1, the association of suppressor of cytokine signaling 3 to the insulin receptor in liver and the rise in glycemia induced by central insulin. Leptin also decreased hepatic phosphoenolpyruvate carboxykinase levels and increased insulin's ability to phosphorylate insulin receptor substrate-1, Akt and glycogen synthase kinase on Ser9 and to stimulate glucose transporter 2 and glycogen levels. Peripheral leptin treatment reproduced some of these changes, but to a lesser extent. Our data indicate that leptin increases the hepatic response to a rise in insulin, suggesting that pharmacological manipulation of leptin targets may be of interest for controlling glycemia. PMID:26296906

  13. Continuous infusion of low-dose doxorubicin, epirubicin and mitoxantrone in cancer chemotherapy: a review.

    PubMed

    Greidanus, J; Willemse, P H; Uges, D R; Oremus, E T; De Langen, Z J; De Vries, E G

    1988-12-01

    With the recent development of reliable portable pumps and safe venous access systems, continuous infusion of chemotherapeutic agents on an out-patient basis has become feasible. Advantages of continuous infusion are the long-term exposure of tumour cells to the drug and the fact that most toxic effects are reduced for doxorubicin, epirubicin and mitoxantrone due to elimination of the high peak plasma levels. Preliminary data for doxorubicin suggest that its antitumour activity is maintained. Pharmacokinetic studies with epirubicin and mitoxantrone showed a linear relationship between drug dose infused and the steady-state plasma level for these drugs. The area under the curve for leukocytes drug level was higher during continuous infusion than after an equitoxic bolus injection of epirubicin and mitoxantrone. Well-randomized clinical trials will be necessary to investigate the role of continuous infusion of antracyclines and mitoxantrone in cancer chemotherapy in the future. PMID:3062572

  14. Tolerance to cocaine in brain stimulation reward following continuous cocaine infusions.

    PubMed

    Pudiak, Cindy M; KuoLee, Rhonda; Bozarth, Michael A

    2014-07-01

    This study examined tolerance to cocaine's threshold-lowering effect in brain stimulation reward (BSR) following continuous cocaine infusions and secondly, used the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) to determine NO's involvement in the development of cocaine tolerance. Animals were continuously infused with saline or cocaine (30 mg/kg per day) via osmotic minipump for 14 days and injected daily with saline or L-NAME (30 mg/kg, i.p.) following BSR testing. Saline-treated animals continuously infused with saline showed stable BSR thresholds across the 14-day infusion period. Saline-treated animals continuously infused with cocaine showed markedly lowered BSR thresholds on Day 1 followed by a progressive increase in BSR thresholds across the infusion period - indicating the development of tolerance. L-NAME-treated animals continuously infused with cocaine showed stimulation thresholds that were not significantly different from saline-treated animals continuously infused with cocaine. A cocaine challenge injection (10 mg/kg, i.p.) administered 3 and again at 10 days following minipump removal revealed that saline-treated animals continuously infused with saline showed lowered BSR thresholds. Saline-treated animals continuously infused with cocaine displayed lowered BSR thresholds that were not significantly different from saline-infused animals. L-NAME treated animals continuously infused with cocaine showed higher BSR thresholds to a challenge 3 days following pump removal. However, stimulation thresholds for this group failed to reach statistical significance on both days (i.e., Days 3 and 10) following pump removal. Results showed that animals continuously infused with cocaine develop robust tolerance to cocaine's threshold-lowering effect during the 14-day infusion period. Tolerance to cocaine's threshold-lowering effect was short-lived and dissipated soon after minipump removal. L-NAME treatment failed to significantly

  15. Human hippocampal energy metabolism is impaired during cognitive activity in a lipid infusion model of insulin resistance

    PubMed Central

    Emmanuel, Yaso; Cochlin, Lowri E; Tyler, Damian J; de Jager, Celeste A; David Smith, A; Clarke, Kieran

    2013-01-01

    Neuronal glucose uptake was thought to be independent of insulin, being facilitated by glucose transporters GLUT1 and GLUT3, which do not require insulin signaling. However, it is now known that components of the insulin-mediated glucose uptake pathway, including neuronal insulin synthesis and the insulin-dependent glucose transporter GLUT4, are present in brain tissue, particularly in the hippocampus. There is considerable recent evidence that insulin signaling is crucial to optimal hippocampal function. The physiological basis, however, is not clear. We propose that while noninsulin-dependent GLUT1 and GLUT3 transport is adequate for resting needs, the surge in energy use during sustained cognitive activity requires the additional induction of insulin-signaled GLUT4 transport. We studied hippocampal high-energy phosphate metabolism in eight healthy volunteers, using a lipid infusion protocol to inhibit insulin signaling. Contrary to conventional wisdom, it is now known that free fatty acids do cross the blood–brain barrier in significant amounts. Energy metabolism within the hippocampus was assessed during standardized cognitive activity. 31Phosphorus magnetic resonance spectroscopy was used to determine the phosphocreatine (PCr)-to-adenosine triphosphate (ATP) ratio. This ratio reflects cellular energy production in relation to concurrent cellular energy expenditure. With lipid infusion, the ratio was significantly reduced during cognitive activity (PCr/ATP 1.0 ± 0.4 compared with 1.4 ± 0.4 before infusion, P = 0.01). Without lipid infusion, there was no reduction in the ratio during cognitive activity (PCr/ATP 1.5 ± 0.3 compared with 1.4 ± 0.4, P = 0.57). This provides supporting evidence for a physiological role for insulin signaling in facilitating increased neuronal glucose uptake during sustained cognitive activity. Loss of this response, as may occur in type 2 diabetes, would lead to insufficient neuronal energy availability during cognitive activity

  16. Effect of continuous regional vasoactive agent infusion on liver metastasis blood flow.

    PubMed Central

    Dworkin, M. J.; Carnochan, P.; Allen-Mersh, T. G.

    1997-01-01

    Regionally administered vasopressors might increase tumour chemotherapy uptake by differentially constricting normal and tumour blood vessels, leading to a selective increase in blood flow to the tumour. In this study, we compared the effects of the vasopressors angiotensin II, vasopressin and endothelin I and the vasodilator calcitonin gene-related peptide (CGRP) by continuously measuring liver parenchymal and tumour blood flow during a 30-min regional vasoactive infusion in a rat HSN liver metastasis model. Vasopressin and angiotensin II produced a vasoconstriction that decreased despite continued infusion, while endothelin I infusion led to prolonged vasoconstriction with a more gradual onset. CGRP infusion resulted in increased vessel conductance but a reduction in blood flow due to systemic hypotension. The tumour to normal flow ratio (TNR) was transiently increased during infusion of all pressors, but only endothelin I produced sufficient change to result in a rise in average TNR throughout pressor infusion. Continuous liver and tumour blood flow measurement throughout vasoactive infusion demonstrated that the extent and the duration of blood flow change varied with the agents assessed. No vasoactive agent increased tumour blood flow, but endothelin I had the most suitable vasoactive properties for enhancing tumour uptake of continuously infused chemotherapy. PMID:9365170

  17. 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

  18. Use of Continuous Infusion Pumps During Radiation Treatment

    PubMed Central

    Bak, Kate; Gutierrez, Eric; Lockhart, Elizabeth; Sharpe, Michael; Green, Esther; Costa, Sarah; Hertz, Sherrie; Kaizer, Leonard; Whitton, Anthtony; Warde, Padraig

    2013-01-01

    Introduction: Despite increasing chemoradiotherapy treatment, there is a paucity of information regarding the effects of radiation exposure on ambulatory infusion pumps used to deliver chemotherapy or other essential medications. The aim of this overview is to present the available evidence on this subject, heighten awareness within the clinical community, provide considerations for minimizing possible negative effects on patient care, and encourage the monitoring of infusion devices after exposure to radiation or electromagnetic interference. Methods: Published literature was systematically searched using MEDLINE and EMBASE; gray literature was searched using Google and an environmental scan of relevant Web sites. A multidisciplinary working group reviewed the compiled evidence, and a draft of the document was sent to health professionals from various disciplines for an external review. Results: Four reports and three manufacturer device alerts were identified that suggest a risk of pump malfunction as a result of radiation exposure. The estimated cumulative dose at which pump failure has been reported ranges from 28.5 to 42 Gy; however, additional clinical investigations should be undertaken. Pump relocation, pump shielding, and assessment of the pump after radiation exposure are most commonly suggested to minimize pump malfunction related to radiation exposure. A list of additional considerations is offered for those developing institution specific policies and procedures based on the available evidence and expert consensus. Conclusion: The varied and unpredictable results of radiation exposure on infusion devices suggest that additional testing should be carried out to determine the limits of dose exposure and to raise awareness around this patient safety issue. PMID:23814520

  19. Rescue therapy with terlipressin by continuous infusion in a child with catecholamine-resistant septic shock.

    PubMed

    Zeballos, Gonzalo; López-Herce, Jesús; Fernández, Carmen; Brandstrup, Kay B; Rodríguez-Núñez, Antonio

    2006-01-01

    A 2-month-old female infant presented with septic shock, refractory to high doses of catecholamines. Continuous infusion of terlipressin at a rate of 10 mcg/kgh produced a significant increase in the mean arterial pressure that was evident within half and hour, so allowing a reduction in the rate of catecholamine infusion. However, 18 h later, the blood pressure fell again and finally the patient died. This case shows the potential value of terlipressin infusion to restore normal mean arterial pressure in children with vasodilatory shock and hypotension refractory to catecholamines. PMID:16325320

  20. Regulation of de novo hepatic lipogenesis by insulin infusion in rainbow trout fed a high-carbohydrate diet.

    PubMed

    Polakof, S; Médale, F; Larroquet, L; Vachot, C; Corraze, G; Panserat, S

    2011-10-01

    Carbohydrate energy intake in excess of total energy expenditure is converted to fat. In fish, the liver is considered to be the main lipogenic tissue. Its regulation by insulin is not fully understood, and some of the available in vivo findings are contradictory. In this study, bovine insulin was infused for 5 d into rainbow trout fed a high-carbohydrate diet, and variables of de novo hepatic lipogenesis were measured. We found that hepatic lipogenesis in trout is stimulated by insulin, reflected in enhanced mRNA and protein abundance and enzyme activity of ATP-citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase. These results were further supported by parallel changes in enzymes acting as NAD phosphate donors, especially those participating in the pentose phosphate pathway. This is the first time that the main enzymes involved in de novo hepatic lipogenesis have been studied at the molecular, protein, and activity levels in fish. We hypothesize that some of the delayed changes found in the different levels of regulation were probably related to the insulin resistance achieved by the trout liver after 5 d of insulin infusion. We assessed enzyme activity and mRNA abundance of lipid oxidation-related enzymes in the livers of insulin-infused fish in which paradoxically increased β-oxidation potential was found. The insulin-stimulated de novo hepatic lipogenesis in carbohydrate-fed trout reinforces the hypothesis that this pathway may act as an important sink for excess glucose, which could ultimately contribute to improved glucose homeostasis in this carnivorous and glucose-intolerant species when fed high-carbohydrate diets. PMID:21571891

  1. In silico evaluation of a control system and algorithm for automated insulin infusion in the ICU setting

    PubMed Central

    2010-01-01

    Background It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS) for inpatient treatment, and tested its stability under simulated clinical conditions. Methods The system included: reference glucose, glucose sensor, insulin and glucose infusion controllers and emergency infusion logic. We carried out computer simulations using Matlab/Simulink®, in both common and worst-case conditions. Results The system was capable of controlling glucose levels without entering in a phase of catastrophic instability, even under severe simulated challenges. Care was taken to include in all simulations the 5-10 minute delay of the subcutaneous glucose signal when compared to the real-time serum glucose signal, a well-known characteristic of all subcutaneous glucose sensors. Conclusions When tested in-Silico, a commercially available subcutaneous glucose sensor allowed the stable functioning of a proportional-derivative Automatic Insulin Infusion System, which was able to maintain glucose within acceptable limits when using a well-established glucose response model simulating a patient. Testing of the system in vivo using animal models is now warranted. PMID:20642855

  2. 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

  3. Dialysis Access Graft Thrombolysis: Randomized Study of Pulse-Spray Versus Continuous Urokinase Infusion

    SciTech Connect

    Goodwin, Scott C.; Arora, Lokesh C.; Razavi, Mahmood K.; Sayre, James; McNamara, Thomas O.; Yoon, Chun

    1998-03-15

    Purpose: To compare pulse-spray to continuous-infusion thrombolysis with high-dose urokinase in thrombosed dialysis access grafts. Methods: A prospective randomized controlled trial was performed. From August 1992 to September 1993, 30 thrombosed polytetrafluoroethylene (PTFE) grafts in 24 patients were included, 15 grafts in each group. The success of thrombolysis, mean time to thrombolysis, mean urokinase dose, and 60-day patency rate were evaluated. Results: In the pulse-spray group, the mean time to thrombolysis was 72 min with a mean urokinase dose of 560,000 U. The 60-day patency rate was 71%. In the continuous-infusion group, the mean infusion time to thrombolysis was 55 min with a mean dose of 479,000 U. The 60-day patency rate was 73%. Conclusion: No statistically significant difference was found between the two techniques in the mean time to thrombolysis, the mean urokinase dose used, or the 60-day patency rate.

  4. High-dose continuous infusion plus pulse interleukin-2 and famotidine in melanoma.

    PubMed

    Quan, Walter; Ramirez, Maria; Taylor, W Chris; Vinogradov, Mikhail; Khan, Nawazish; Jackson, Shawn

    2004-12-01

    High-dose, continuous infusion interleukin-2 (IL-2) regimens generate greater Lymphokine Activated Killer cell (LAK) cytotoxicity in vitro and a higher rebound lymphocytosis in vivo than do bolus IL-2 regimens. Lymphocytes initially activated by continuous infusion IL-2 then subsequently pulsed with IL-2 have increased cytotoxicity against cancer cells. Famotidine may enhance the lysis of tumors by cytotoxic lymphocytes. Fourteen patients with melanoma were treated with famotidine 20 mg intravenously twice per day and continuous infusion IL-2 (18 MIU/sq m/24 hours) for 72 hours, followed by a 24-hour rest, then IL-2 18 MIU/sq m over 15-30 minutes for 1 dose (12 patients) or daily for 3 doses (2 patients). Most common toxicities were fever, nausea/emesis, hypophosphatemia, hypomagnesemia, and rigors. Nine partial responses (64% response rate; 95% Confidence Interval: 39%-84%) have been seen. Median survival has not been reached at greater than 10 months. Two patients responding to therapy showed an increase in detectable CD 56(+) cells in serial subcutaneous or lymph node biopsies, while 1 patient undergoing progression of disease had no such infiltrate. High-dose, 72-hour continuous infusion plus pulse interleukin-2 with famotidine has activity in melanoma. CD 56(+) cells may play a role in responding patients. PMID:15665626

  5. High-dose continuous infusion plus pulse interleukin-2 and famotidine in metastatic kidney cancer.

    PubMed

    Quan, Walter; Ramirez, Maria; Taylor, Chris; Vinogradov, Mikhail; Quan, Francine; Khan, Nawazish

    2005-02-01

    High-dose continuous infusion interleukin-2 (IL-2) regimens generate a higher degree of lymphokine activated killer cell (LAK) cytotoxicity when tested against tumor cells in vitro and a higher rebound lymphocytosis in vivo than do bolus IL-2 regimens. Lymphocytes initially activated by continuous infusion IL-2 have increased cytotoxicity against cancer cells when they are subsequently pulsed with additional IL-2. Famotidine may enhance LAK cytolytic ability. Six patients with kidney cancer have been treated with a combination of famotidine 20 mg intravenous bid and continuous infusion IL-2 (18 MIU/sq m/24 hours) for 72 hours, followed by a 24-hour rest, then IL-2 18 MIU/sq m over 15-30 minutes. The most common metastatic sites were the lung, lymph node, and bone. Median number of cycles received = 5 (range, 3-8). The most common toxicities were fever, rigors, nausea/emesis, hypophosphatemia, hypotension, elevated creatinine, and metabolic acidosis. There were no treatment-related deaths, and no patients required intensive care admission. Two partial responses (33% response rate) have been seen. Median survival has not been reached at greater than 8 months. The combination of high-dose continuous infusion plus pulse IL-2 and famotidine is active in metastatic kidney cancer. An accrual of additional patients is needed to better assess the response rate. PMID:15778577

  6. Bolus dose with continuous infusion of midazolam as sedation for outpatient surgery.

    PubMed

    Luyk, N H; Zacharias, M; Wanwimolaruk, S

    1992-06-01

    This double-blind, randomised, cross-over trial in 41 patients for 3rd molar surgery compared the safety, amnesic properties and psychomotor recovery between a bolus injection of midazolam and a bolus injection followed by continuous infusion of midazolam. The latter showed good safety and better amnesia to events during the procedure, but prolonged the recovery time. PMID:1640130

  7. Vascular Access System for Continuous Arterial Infusion of a Protease Inhibitor in Acute Necrotizing Pancreatitis

    SciTech Connect

    Ganaha, Fumikiyo; Yamada, Tetsuhisa; Yorozu, Naoya; Ujita, Masuo; Irie, Takeo; Fukuda, Yasushi; Fukuda, Kunihiko; Tada, Shimpei

    1999-09-15

    We used a vascular access system (VAS) for continuous arterial infusion (CAI) of a protease inhibitor in two patients with acute necrotizing pancreatitis. The infusion catheter was placed into the dorsal pancreatic artery in the first patient and into the gastroduodenal artery in the second, via a femoral artery approach. An implantable port was then connected to the catheter and was secured in a subcutaneous pocket prepared in the right lower abdomen. No complications related to the VAS were encountered. This system provided safe and uncontaminated vascular access for successful CAI for acute pancreatitis.

  8. Continuous subcutaneous infusion of lidocaine for persistent hiccup in advanced cancer.

    PubMed

    Kaneishi, Keisuke; Kawabata, Masahiro

    2013-03-01

    Persistent hiccup can cause anorexia, weight loss, disabling sleep deprivation, anxiety, and depression. Therefore, relief of persistent hiccup is important for advanced cancer patients and their family. Most reports on this condition are case series reports advocating the use of baclofen, haloperidol, gabapentin, and midazolam. However, these medications are occasionally ineffective or accompanied by intolerable side effects. The sodium channel blocker lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms. Intravenous administration of lidocaine is common but efficacy has also been reported for subcutaneous infusion. In advanced cancer patients, subcutaneous infusion is easy, advantageous, and accompanied by less discomfort. We report a case of severe and sustained hiccup caused by gastric cancer that was successfully treated with a continuous subcutaneous infusion of lidocaine (480 mg (24 ml)/day) without severe side effects. PMID:22661318

  9. Cyclic ethanol metabolism in hypophysectomized rats continuously infused alcohol-containing diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic ethanol (EtOH) intake induces hepatic alcohol dehydrogenase (ADH) expression via disruption of insulin signaling in liver (JBC 2006; 281:1126-34). Total enteral nutrition (TEN) is a method of slow and continuous (approx. 23/day) feeding patients through an intragastric tube. Rats fed EtOH-co...

  10. Cerebral blood flow with the continuous infusion of oxygen-15-labeled water

    SciTech Connect

    Jones, S.C.; Greenberg, J.H.; Dann, R.; Robinson, G.D. Jr.; Kushner, M.; Alavi, A.; Reivich, M.

    1985-12-01

    This work describes the determination of CBF in eight normal human subjects with positron emission tomographic (PET) imaging using the continuous intravenous infusion of H2(15)O. A whole-brain CBF model is described that permits the comparison of the CBF values determined using PET with those obtained using other methods. This model includes a correction for whole-brain recovery coefficient, a correction for the underestimation of flow due to the nonlinearity of the CBF model when considering tissue that includes both gray and white matter, the use of in vitro-determined brain-blood partition coefficients for gray and white matter, and a variation of the equilibrium model that permits the arterial concentration to vary. CBF values using this method compare well with values determined previously. Regional determinations using a brain overlay atlas are presented. Radiation dosimetry for the continuous infusion of H2(15)O is also included.

  11. Continuously Infusing Hyperpolarized 129Xe into Flowing Aqueous Solutions Using Hydrophobic Gas Exchange Membranes

    PubMed Central

    Cleveland, Zackary I.; Möller, Harald E.; Hedlund, Laurence W.; Driehuys, Bastiaan

    2009-01-01

    Hyperpolarized (HP) 129Xe yields high signal intensities in magnetic resonance (MR) and, through its large chemical shift range of ∼300 ppm, provides detailed information about the local chemical environment. To exploit these properties in aqueous solutions and living tissues requires the development of methods for efficiently dissolving HP 129Xe over an extended time period. To this end, we have used commercially available gas exchange modules to continuously infuse concentrated HP 129Xe into flowing liquids, including rat whole blood, for periods as long as one hour, and have demonstrated the feasibility of dissolved-phase MR imaging with sub-millimeter resolution within minutes. These modules, which exchange gases using hydrophobic microporous polymer membranes, are compatible with a variety of liquids and are suitable for infusing HP 129Xe into the bloodstream in vivo. Additionally, we have developed a detailed mathematical model of the infused HP 129Xe signal dynamics that should be useful in designing improved infusion systems that yield even higher dissolved HP 129Xe signal intensities. PMID:19702286

  12. Pharmacokinetics and Pharmacodynamics of Continuous-Infusion Meropenem in Pediatric Hematopoietic Stem Cell Transplant Patients

    PubMed Central

    Cojutti, Piergiorgio; Maximova, Natalia

    2015-01-01

    This study explored the pharmacokinetics and the pharmacodynamics of continuous-infusion meropenem in a population of pediatric hematopoietic stem cell transplant (HSCT) patients who underwent therapeutic drug monitoring. The relationship between meropenem clearance (CLM) and estimated creatinine clearance (CLCR) was assessed by nonlinear regression. A Monte Carlo simulation was performed to investigate the predictive performance of five dosing regimens (15 to 90 mg/kg of body weight/day) for the empirical treatment of severe Gram-negative-related infections in relation to four different categories of renal function. The optimal target was defined as a probability of target attainment (PTA) of ≥90% at steady-state concentration-to-MIC ratios (CSS/MIC) of ≥1 and ≥4 for MICs of up to 8 mg/liter. A total of 21 patients with 44 meropenem CSS were included. A good relationship between CLM and estimated CLCR was observed (r2 = 0.733). Simulations showed that at an MIC of 2 mg/liter, the administration of continuous-infusion meropenem at doses of 15, 30, 45, and 60 mg/kg/day may achieve a PTA of ≥90% at a CSS/MIC ratio of ≥4 in the CLCR categories of 40 to <80, 80 to <120, 120 to <200, and 200 to <300 ml/min/1.73 m2, respectively. At an MIC of 8 mg/liter, doses of up to 90 mg/kg/day by continuous infusion may achieve optimal PTA only in the CLCR categories of 40 to <80 and 80 to <120 ml/min/1.73 m2. Continuous-infusion meropenem at dosages up to 90 mg/kg/day might be effective for optimal treatment of severe Gram-negative-related infections in pediatric HSCT patients, even when caused by carbapenem-resistant pathogens with an MIC of up to 8 mg/liter. PMID:26124157

  13. Activity of continuous infusion + pulse interleukin-2 with famotidine in metastatic melanoma.

    PubMed

    Quan, Walter D Y; Quan, Francine M

    2009-02-01

    High-dose interleukin-2 (IL-2), given via continuous intravenous (i.v.) infusion, induces lymphokine-activated killer (LAK) cell cytotoxicity against tumor cells. These LAKs exhibit enhanced cytotoxicity against tumor cells in vitro when they are subsequently pulsed with additional IL-2. Famotidine may increase LAK cytotoxicity against neoplastic cells by allowing for greater IL-2 uptake at the IL-2 receptor on lymphocytes. Twenty-three (23) patients received famotidine 20 mg i.v. twice per day and continuous-infusion IL-2 (18 MIU/m(2)/24 hours) for 72 hours, followed by a 24-hour rest, then 1-3 daily-pulse IL-2 doses of 18 MIU/m(2) over 15-30 minutes preceded by famotidine 20 mg i.v. Cycles were repeated every 3 weeks. The most common metastatic sites were lung, lymph node, and subcutaneous/soft tissue. The most common toxicities were fever, rigor, nausea/emesis, hypophosphatemia, hypotension, elevated creatinine, and pulmonary edema. There were no treatment-related deaths. One (1) complete (4%) and 9 partial responses (39%) were seen (43% total response rate; 95% confidence interval: 22%-65%). Median survival for all patients is 13 months. The combination of famotidine and high-dose continuous infusion + pulse IL-2 is active in metastatic melanoma. PMID:19243244

  14. Pharmacokinetics of ketamine and propofol combination administered as ketofol via continuous infusion in cats.

    PubMed

    Zonca, A; Ravasio, G; Gallo, M; Montesissa, C; Carli, S; Villa, R; Cagnardi, P

    2012-12-01

    The pharmacokinetics of the extemporaneous combination of low doses of ketamine and propofol, known as 'ketofol', frequently used for emergency procedures in humans to achieve safe sedation and analgesia was studied in cats. The study was performed to assess propofol, ketamine and norketamine kinetics in six female cats that received ketamine and propofol (1:1 ratio) as a loading dose (2 mg/kg each, IV) followed by a continuous infusion (10 mg/kg/h each, IV, 25 min of length). Blood samples were collected during the infusion period and up to 24 h afterwards. Drug quantification was achieved by HPLC analysis using UV-visible detection for ketamine and fluorimetric detection for propofol. The pharmacokinetic parameters were deduced by a two-compartment bolus plus infusion model for propofol and ketamine and a monocompartmental model for norketamine. Additional data were derived by a noncompartmental analysis. Propofol and ketamine were quantifiable in most animals until 24 and 8 h after the end of infusion, respectively. Propofol showed a long elimination half-life (t(1/2λ2) 7.55 ± 9.86 h), whereas ketamine was characterized by shorter half-life (t(1/2λ2) 4 ± 3.4 h) owing to its rapid biotransformation into norketamine. The clinical significance of propofol's long elimination half-life and low clearance is negligible when the drug is administered as short-term and low-dosage infusion. The concurrent administration of ketamine and propofol in cats did not produce adverse effects although it was not possible to exclude interference in the metabolism. PMID:22283551

  15. Repeated cycles with 72-hour continuous infusion interleukin-2 in kidney cancer and melanoma.

    PubMed

    Quan, Walter; Brick, Wendy; Vinogradov, Mikhail; Taylor, W Chris; Khan, Nawazish; Burgess, Russell

    2004-06-01

    While high-dose bolus inpatient interleukin-2 is generally given on 8-week cycles, continuous infusion interleukin-2 could potentially allow for more rapidly repeated cycles. Fourteen (14) patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, having either kidney cancer (6) or melanoma (8), have been treated with continuous infusion (CIV) interleukin-2 (IL-2) 18 MIU/m(2)/24 hours for 72 hours. Cycles were repeated every 3 weeks up to 4 cycles, then every 3-4 weeks for 2 cycles, then every 6-8 weeks, until progression or intolerable toxicity. All patients received famotidine 20 mg intravenously (i.v.) twice per day during the 72-hour infusions. Patient characteristics included a median ECOG performance status of 1; median age = 63 (range: 25-79); most common metastatic sites: lung (9), bone (5), lymph nodes (5), and the liver (3). No patients with metastatic kidney cancer underwent a nephrectomy prior to interleukin-2. Median number of cycles received = 5 (1-9). No patients required Intensive Care Unit (ICU) admission. There have been no treatment-related deaths. Most common toxicities have been rigors, fever, nausea/emesis, and the reversible elevation of creatinine. One complete response and three partial responses (67% response rate; 95% confidence interval: 30%-90%) have been seen in kidney cancer, and two partial responses (25% response rate; 95% confidence interval: 7%-60%) have occurred in melanoma. Median survival has not been reached at >9+ months. Responding sites include the liver, bone, lung, lymph node and subcutaneous sites. Inpatient 72-hour continuous infusion interleukin-2 at this dose and schedule is well tolerated by patients with an ECOG performance status of 0 or 1 and has activity in kidney cancer and melanoma. PMID:15285881

  16. The Effects of Propofol and Thiopental Continuous Infusion on Serum Potassium Disturbances in Neurosurgical Patients

    PubMed Central

    Kim, Tae Kyong; Lim, Young-Jin; Ju, Jae-Woo; Kim, Jin Wook

    2015-01-01

    Objective The potassium disturbance associated with thiopental continuous infusion in neurosurgical patients is well known. However, the effect of propofol continuous infusion on serum potassium levels has not been investigated extensively. Methods We reviewed the medical records of 60 consecutive patients who received coma therapy or deep sedation for intracranial pressure control using either thiopental or propofol between January 2010 and January 2012. Results The overall incidence of hypokalemia (K<3.5 mmol/L) was comparable between thiopental and propofol groups (89.2% vs. 82.6%). But, the incidence of moderate to severe hypokalemia (K<3.0 mmol/L) was significantly higher in thiopental group (51.4% vs. 13.0%, p=0.003). The lowest potassium level (2.9 mmol/L vs. 3.2 mmol/L, p=0.020) was lower in thiopental group. The patients in the thiopental group required greater potassium replacement than the propofol group patients (0.08 mmol/kg/h vs. 0.02 mmol/kg/h, p<0.001). On multivariate analysis, thiopental [odds ratio, 95% confidence interval, 7.31 (1.78-27.81); p=0.005] was associated with moderate to severe hypokalemia during continuous infusion. The incidence of rebound hyperkalemia (K>5.0 mmol/L, 32.4% vs. 4.3%, p=0.010) and the peak potassium concentration (4.8 mmol/L vs. 4.2 mmol/L, p=0.037) after the cessation of therapy were higher in thiopental group. On multivariate analysis, thiopental [8.82 (1.00-77.81); p=0.049] and duration of continuous infusion [1.02 (1.00-1.04); p=0.016] were associated with rebound hyperkalemia once therapy was discontinued. Conclusion Propofol was less frequently associated with moderate to severe hypokalemia after induction and rebound hyperkalemia following the cessation of continuous infusion than thiopental. PMID:25810860

  17. The use of dexmedetomidine continuous rate infusion for horses undergoing transvenous electrical cardioversion — A case series

    PubMed Central

    Marly-Voquer, Charlotte; Schwarzwald, Colin C.; Bettschart-Wolfensberger, Regula

    2016-01-01

    Five horses were presented for treatment of atrial fibrillation by transvenous electrical cardioversion (TVEC). A dexmedetomidine infusion was administered for sedation during positioning of the cardioversion catheters, and continued during general anesthesia. Shocks were applied until return to sinus rhythm. Dexmedetomidine infusion provided excellent conditions for TVEC catheter placement and procedure. PMID:26740702

  18. Pilot study of interaction of radiation therapy with doxorubicin by continuous infusion

    SciTech Connect

    Rosenthal, C.J.; Rotman, M.

    1988-01-01

    Doxorubicin was initially administered alone by continuous infusion for 5 days every 3 weeks in escalating doses to 13 patients with advanced metastatic and/or recurrent malignancies. The maximum tolerable dosage was 13 mg/m2 per day for 5 days. Kinetic data showed a steady level of 60 ng/ml for 4 days and a biphasic disappearance curve. Radiation therapy (150-200 cGy per session) was then administered in 5-day cycles, every 3 weeks, concomitantly with continuous infusion of doxorubicin (12 mg/m2 per day) to 21 patients with various advanced unresectable recurrent or metastatic malignancies. Four of 9 patients with soft tissue sarcomas achieved complete response after a radiation dose of 2,206 +/- 590 (SD) cGy and 3 had partial response; the median durations of the response were 142 +/- 65 (SD) weeks for complete response and 28 +/- 10 weeks for partial response. Of 4 patients with primary hepatoma, 2 achieved partial response after 1,290 +/- 210 cGy. No response was seen in any of the 7 patients with adenocarcinoma of the gastrointestinal tract or breast. Complications of this regimen included moderate leukopenia and thrombocytopenia, mucositis, skin erythema, and decrease of the ventricular ejection fraction at a cumulative doxorubicin dose of 840 mg/m2. We conclude that doxorubicin given by protracted infusion can be safely administered with concomitant radiation and appears to enhance the effects of radiation on most soft tissue sarcomas and on some hepatocellular carcinomas.

  19. Circadian continuous chemotherapy of renal cell carcinoma with an implantable, programmable infusion pump.

    PubMed

    Damascelli, B; Marchianò, A; Spreafico, C; Lutman, R; Salvetti, M; Bonalumi, M G; Mauri, M; Garbagnati, F; Del Nero, A; Comeri, G

    1990-07-15

    The authors treated 42 metastatic renal cell carcinoma (RCC) patients who had received no previous chemotherapy or radiation therapy with circadian venous continuous infusion of 5-fluoro-2-deoxyuridine (FUDR). The drug was delivered by Medtronic Synchromed implantable pump (Medtronic, Inc., Minneapolis, MN) in 14-day cycles alternating with 14-day intervals of heparinized physiologic saline infusion. In the course of 24 months 444 cycles of therapy have been given for a total of 12449 days of pump function. Of the patients observed for at least 3 months (range, 3 to 23 months; median, 7 months) three showed complete response (7%; 95% confidence interval, 0% to 15%), three partial response (7%; confidence interval, 0% to 15%), 18 stable disease, and 18 showed progression. Eighteen patients, all with advanced disease at the time of implantation, were living 6 months after treatment started. Circadian continuous central venous infusion of FUDR is minimally toxic. The FUDR can be delivered safely and conveniently in this way for long spans. This therapy is as active as any currently available treatment, is administered in an entirely outpatient setting, and is associated with a normal quality of life. PMID:2142443

  20. Flexibility and efficacy of automatic continuous fluorodeoxyuridine infusion in metastases from a renal cell carcinoma.

    PubMed

    Damascelli, B; Marchianò, A; Frigerio, L F; Salvetti, M; Spreafico, C; Garbagnati, F; Zanoni, F; Radice, F

    1991-09-01

    Complete and lasting control of diffuse metastases from a renal cell carcinoma has been achieved by automatic continuous infusion of a single cytotoxic agent, fluorodeoxyuridine (FUDR). A patient with a single brain metastasis from renal cell carcinoma developed pulmonary, mediastinal, and retroperitoneal metastases after radical nephrectomy. A Medtronic Synchromed pump (Medtronic Inc., Minneapolis, MN) was implanted for the circadian systemic infusion of FUDR in 14-day courses with 14-day drug-free intervals. A complete response (CR) at all sites, was obtained in 3 months, and maintained for 22 months. After a second brain metastasis, treated by radiation therapy and cisplatin as radiosensitizer, a CR was obtained again and is now of 31 months' duration, which is four times the record to date. The overall hospitalization was 2 days. Acceptance of the pump is excellent and it functions precisely and reliably. This case should stimulate greater interest in techniques of automatic continuous infusion of cytostatics, given its greater efficacy and lower toxicity. PMID:1833043

  1. Continuous versus intermittent infusion of vancomycin in adult patients: A systematic review and meta-analysis.

    PubMed

    Hao, Jing-Jing; Chen, Han; Zhou, Jian-Xin

    2016-01-01

    Continuous infusion of vancomycin (CIV) and intermittent infusion of vancomycin (IIV) are two major administration strategies in clinical settings. However, previous articles comparing the efficacy and safety of CIV versus IIV showed inconsistent results. Therefore, a meta-analysis was conducted to compare the efficacy and safety of CIV and IIV. PubMed, the Cochrane Library and Web of Science up to June 2015 were searched using the keywords 'vancomycin', 'intravenous', 'parenteral', 'continuous', 'intermittent', 'discontinuous', 'infusion', 'administration' and 'dosing'. Eleven studies were included in the meta-analysis. Neither heterogeneity nor publication bias were observed. Patients treated with CIV had a significantly lower incidence of nephrotoxicity compared with patients receiving IIV [risk ratio (RR)=0.61, 95% confidence interval (CI) 0.47-0.80; P<0.001]. No significant difference in treatment failure between the two groups was detected. Mortality between patients receiving CIV and patients receiving IIV was similar (RR=1.15, 95% CI 0.85-1.54; P=0.365). This meta-analysis showed that CIV had superior safety compared with IIV, whilst the clinical efficacy was not significantly different. A further multicentre, randomised controlled trial is required to confirm these results. PMID:26655032

  2. A Mathematical Model for Comparison of Bolus Injection, Continuous Infusion, and Liposomal Delivery of Doxorubicin to Tumor Cells1

    PubMed Central

    El-Kareh, Ardith W; Secomb, Timothy W

    2000-01-01

    Abstract Determining the optimal mode of delivery for doxorubicin is important given the wide use of the drug against many tumor types. The relative performances of bolus injection, continuous infusion, liposomal and thermoliposomal delivery are not yet definitely established from clinical trials. Here, a mathematical model is used to compare bolus injection, continuous infusion for various durations, liposomal and thermoliposomal delivery of doxorubicin. Effects of the relatively slow rate, and saturability, of doxorubicin uptake by cells are included. Peak concentrations attained in tumor cells are predicted and used as a measure of antitumor effectiveness. To measure toxicity, plasma area under the curve (AUC) and peak plasma concentrations of free doxorubicin are computed. For continuous infusion, the duration of infusion significantly affects predicted outcome. The optimal infusion duration increases with dose, and is in the range 1 to 3 hours at typical doses. The simulations suggest that continuous infusion for optimal durations is superior to the other protocols. Nonthermosensitive liposomes approach the efficacy of continuous infusion only if they release drug at optimal rates. Predictions for thermosensitive liposomes indicate a potential advantage at some doses, but only if hyperthermia is applied locally so that the blood is not significantly heated. PMID:11005567

  3. Effect of Heparin on Coagulation Tests: A Comparison of Continuous and Bolus Infusion in Haemodialysis Patients

    PubMed Central

    Nasiri, Ali Akbar; Ahmadidarrehsima, Sudabeh; Balouchi, Abbas; Moghadam, Mahdiye Poodine

    2016-01-01

    Introduction Haemodialysis is one of the most conventional treatments of chronic renal failure. The risk of clot formation is high during haemodialysis due to regular contact of blood with the surfaces of foreign objects such as catheters, dialyzers’ membrane, and other materials used for dialysis. Therefore, to prevent clot formation during haemodialysis, the dialysis system requires anticoagulation; this is usually done by heparin. Aim The present study aimed to compare two heparinization methods and determine the proper impacts of these methods. Materials and Methods In this quasi-experimental study, 80 haemodialysis patients covered by the dialysis center of Amir-al-momenin Hospital of Zabol were studied in two 40-member groups of heparin therapy methods of bolus injection and continuous infusion. PT and PTT were measured in blood samples collected from all patients before starting haemodialysis. The first group received 3000 units of heparin once the haemodialysis machine started to work and 2000 units of heparin two hours later as bolus injection. In the second group, 1500 units of heparin was injected at the start of dialysis after then, 5000 units of heparin (one mL) were mixed with 11 mL of distilled water and infused using a heparin injection pump up to half an hour before the end of dialysis. At 30 minutes after starting dialysis and at the end of 4 hours of haemodialysis, PT and PTT were measured and compared between the two groups. Results According to the results, the mean partial thromboplastin time in the bolus and continuous heparin-receiving group was 41.75±6.29 and 37.90±4.77, respectively, which was statistically significant (p=0.036). But PT was 14.45±1.82 in the bolus heparin group and 13.95±1.39 in the continuous heparin group, which was not significant according to the results of independent t-test (p=0.336). Conclusion The results indicated a statistically significant difference between the bolus heparin injection and the continuous

  4. The analgesic efficacy of continuous presternal bupivacaine infusion through a single catheter after cardiac surgery

    PubMed Central

    Nasr, Dalia Abdelhamid; Abdelhamid, Hadeel Magdy; Mohsen, Mai; Aly, Ahmad Helmy

    2015-01-01

    Background: Median sternotomy, sternal spreading, and sternal wiring are the main causes of pain during the early recovery phase following cardiac surgery. Aim: This study was designed to evaluate the analgesic efficacy of continuous presternal bupivacaine infusion through a single catheter after parasternal block following cardiac surgery. Materials and Methods: The total of 40 patients (American Society of Anesthesiologist status II, III), 45–60 years old, undergoing coronary – artery bypass grafting were enrolled in this prospective, randomized, double-blind study. A presternal catheter was inserted with continuous infusion of 5 mL/h bupivacaine 0.25% (Group B) or normal saline (Group C) during the first 48 postoperative hrs. Primary outcomes were postoperative morphine requirements and pain scores, secondary outcomes were extubation time, postoperative respiratory parameters, incidence of wound infection, Intensive Care Unit (ICU) and hospital stay duration, and bupivacaine level in blood. Statistical Methods: Student's t-test was used to analyze the parametric data and Chi-square test for categorical variables. Results: During the postoperative 48 h, there was marked reduction in morphine requirements in Group B compared to Group C, (8.6 ± 0.94 mg vs. 18.83 ± 3.4 mg respectively, P = 0.2), lower postoperative pain scores, shorter extubation time (117 ± 10 min vs. 195 ± 19 min, respectively, P = 0.03), better respiratory parameters (PaO2/FiO2, PaCO2 and pH), with no incidence of wound infection, no differences in ICU or hospital stay duration. The plasma concentration of bupivacaine remained below the toxic threshold (at T24, 1.2 ug/ml ± 0.3 and T48 h 1.7 ± 0.3 ug/ml). Conclusion: Continuous presternal bupivacaine infusion has resulted in better postoperative analgesia, reduction in morphine requirements, shorter time to extubation, and better postoperative respiratory parameters than the control group. PMID:25566704

  5. Continuous infusion of amphotericin B deoxycholate: an innovative, low-cost strategy in antifungal treatment.

    PubMed

    Falci, Diego R; dos Santos, Rodrigo P; Wirth, Fernanda; Goldani, Luciano Z

    2011-03-01

    The combination of amphotericin B and sodium deoxycholate is the formulation most used in clinical practice. The development of new agents such as amphotericin with lipid formulations, caspofungin, voriconazole and other azolic derivatives, promoted alternatives to amphotericin B deoxycholate. However, because of the high cost of these new drugs, their use is difficult in a scenario of limited resources. A few strategies have been devised to make the use of amphotericin B deoxycholate less toxic. In this review, we seek to describe the accumulated knowledge about this molecule, with focus on its use in continuous infusion, which appears to be an alternative to reduce toxicity, while maintaining its clinical efficacy. PMID:19878457

  6. Optimizing the Concentration and Bolus of a Drug Delivered by Continuous Infusion

    PubMed Central

    Thall, Peter F.; Szabo, Aniko; Nguyen, Hoang Q.; Amlie-Lefond, Catherine M.; Zaidat, Osama O.

    2011-01-01

    Summary We consider treatment regimes in which an agent is administered continuously at a specified concentration until either a response is achieved or a predetermined maximum infusion time is reached. Response is an event defined to characterize therapeutic efficacy. A portion of the maximum planned total amount administered is given as an initial bolus. For such regimes, the amount of the agent received by the patient depends on the time to response. An additional complication when response is evaluated periodically rather than continuously is that the response time is interval censored. We address the problem of designing a clinical trial in which such response time data and a binary indicator of toxicity are used together to jointly optimize the concentration and the size of the bolus. We propose a sequentially adaptive Bayesian design that chooses the optimal treatment for successive patients by maximizing the posterior mean utility of the joint efficacy-toxicity outcome. The methodology is illustrated by a trial in which tissue plasminogen activator is infused intra-arterially as rapid treatment for acute ischemic stroke. PMID:21401568

  7. [Current concept of insulin therapy intensification, and the role of human regular insulin and rapid-acting insulin analogs in insulin treatment].

    PubMed

    Hamaguchi, Tomoya; Sadahiro, Katsuhiko; Satoh, Tomomi

    2015-03-01

    The evolution of insulin therapy from animal insulin to recombinant human regular insulin has improved diabetes treatment. Generating of rapid-acting insulin analogs, mimicking physiologic insulin action enables us to provide better control of post-prandial glucose level and lower incidence of hypoglycemia compared with human regular insulin. These rapid-acting insulin analogs show lower susceptibility of insulin precipitation and catheter occlusions, and are suitable for insulin pump therapy of continuous subcutaneous insulin infusion. Insulin lispro and insulin aspart are also applicable for diabetic patients with pregnancy, requiring excellent glycemic control. In some studies, stepwise addition of prandial insulin, as well as full basal-bolus regimen can improve glycemic control with less hypoglycemia. Treatment intensification with rapid-acting insulin analogs may offer a proper method to reach glycemic goals. PMID:25812371

  8. Kinetics of cell labeling and thymidine replacement after continuous infusion of halogenated pyrimidines in vivo

    SciTech Connect

    Rodriguez, R.; Ritter, M.A.; Fowler, J.F.; Kinsella, T.J. )

    1994-04-30

    The authors present experiments on an in vivo human tumor xenograft continuously exposed to a fixed serum concentration of halogenated pyrimidines so as to study the kinetics of cell labeling and thymidine replacement. Human colon tumor (HCT-116) cells were injected subcutaneously into nude mice. After 10 days, most animals (>90%) developed measurable tumor nodules with a volume doubling time of 5 [+-] 1 days. Once the tumors reached a cross-sectional area of 0.25-0.30 cm[sup 2], miniosmotic pumps were implanted to deliver a dose of 100 mg/kg/day of IdUrd (iododeoxyuridine) by continuous infusion. After an IdUrd exposure time of 1-7 days, blood and tumor tissue were collected. The steady state serum IdUrd concentration was 0.95 [+-] 0.1 [mu]M, which is a clinically relevant concentration for a prolonged continuous intravenous infusion. The tumor cell potential doubling time (T[sub pot]) was 25. The percent IdUrd thymidine replacement and the fraction of cells labeled followed exponential saturation kinetics with a halflife of 33 and 27 h, respectively. After 5 days of exposure, the thymidine replacement in tumor cells was 2.0% and the fraction of tumor cells labeled was 94%. Immunohistochemical staining of IdUrd labeled tumor tissues showed an exposure-dependent gradient of cellular labeling that was initially highest in regions close to blood vessels. After 4 days of exposure at 100 mg/kg/day, there was an increase in the fraction of cells in G[sub 0] + G[sub 1] and a decrease in the S phase population, suggesting a block between G[sub 1] and S phase. They conclude that the in vivo kinetics of IdUrd thymidine replacement and fraction of cells labeled after continuous exposure followed exponential saturation kinetics with a halflife of approximately the potential doubling time of the tumor cell population. Some form of prolonged, or briefly interrupted, continuous infusion should be considered for clinical administration. 48 refs., 5 figs.

  9. Continuous Regional Arterial Infusion Therapy for Acute Necrotizing Pancreatitis Due to Mycoplasma pneumoniae Infection in a Child

    SciTech Connect

    Nakagawa, Motoo Ogino, Hiroyuki; Shimohira, Masashi; Hara, Masaki; Shibamoto, Yuta

    2009-05-15

    A case of acute necrotizing pancreatitis due to Mycoplasma pneumoniae infection was treated in an 8-year-old girl. She experienced acute pancreatitis during treatment for M. pneumoniae. Contrast-enhanced computed tomographic scan revealed necrotizing pancreatitis. The computed tomographic severity index was 8 points (grade E). A protease inhibitor, ulinastatin, was provided via intravenous infusion but was ineffective. Continuous regional arterial infusion therapy was provided with gabexate mesilate (FOY-007, a protease inhibitor) and meropenem trihydrate, and the pancreatitis improved. This case suggests that infusion therapy is safe and useful in treating necrotizing pancreatitis in children.

  10. Continuous Glucose Monitoring Analysis as Predictor of Islet Yield and Insulin Requirements in Autologous Islet Transplantation After Complete Pancreatectomy

    PubMed Central

    Georgiev, George Ivanov; Cercone, Renee; Tiwari, Mukesh; Rilo, Horacio L. R.

    2014-01-01

    We analyzed the pretransplant continuous glucose monitoring (CGM) data of 45 patients that underwent total pancreatectomy followed by autologous islet transplantation (AIT) at the University of Arizona Medical Center. Traditional and novel metrics of CGM time series were correlated to the total islet count (TIC), islet equivalents (IEQs), and weight-normalized IEQs (IEQ/kg). In a subset cohort (n = 26) we analyzed the relationship among the infused number of islets, the CGM indicators, and the first recorded insulin requirement after the procedure. We conclude that receiving a high islet yield is sufficient yet not necessary to achieve low or null insulin requirements within the first 50 days after surgery. Furthermore, CGM inertia and CGM length of curve (2 novel CGM indicators) are shown to be correlated to islet yield, and the CGMs normalized area (Ao) and time ratio above hyperglycemic level (To) are strongly correlated to insulin requirement. A screening test based on To is shown to have 100% sensitivity and 88% specificity discriminating insulin independence upon discharge. PMID:25190081

  11. The Development of Recurrent Seizures after Continuous Intrahippocampal Infusion of Methionine Sulfoximine in Rats

    PubMed Central

    Wang, Yue; Zaveri, Hitten P.; Lee, Tih-Shih W; Eid, Tore

    2009-01-01

    Glutamine synthetase is deficient in astrocytes in the epileptogenic hippocampus in human mesial temporal lobe epilepsy (MTLE). To explore the role of this deficiency in the pathophysiology of MTLE, rats were continuously infused with the glutamine synthetase inhibitor methionine sulfoximine (MSO, 0.625 µg/h) or 0.9% NaCl (saline control) unilaterally into the hippocampus. The seizures caused by MSO were assessed by video-intracranial electroencephalogram (EEG) monitoring. All (28 of 28) of the MSO-treated animals and none (0 of 12) of the saline-treated animals developed recurrent seizures. Most recurrent seizures appeared in clusters of 2 days’ duration (median; range, 1 to 12 days). The first cluster was characterized by frequent, predominantly Stage I seizures, which presented after the first 9.5 h of infusion (median; range, 5.5 to 31.7 h). Subsequent clusters of less-frequent, mainly partial seizures occurred after a clinically silent interval of 7.1 days (median; range, 1.8 to 16.2 days). The ictal intracranial EEGs shared several characteristics with recordings of partial seizures in humans, such as a distinct evolution of the amplitude and frequency of the EEG signal. The neuropathology caused by MSO had similarities to hippocampal sclerosis in 23.1% of cases, whereas 26.9% of the animals had minimal neuronal loss in the hippocampus. Moderate to severe diffuse neuronal loss was observed in 50% of the animals. In conclusion, the model of intrahippocampal MSO infusion replicates key features of human MTLE and may represent a useful tool for further studies of the cellular, molecular and electrophysiological mechanisms of this disorder. PMID:19747915

  12. A low dose euglycemic infusion of recombinant human insulin-like growth factor I rapidly suppresses fasting-enhanced pulsatile growth hormone secretion in humans.

    PubMed Central

    Hartman, M L; Clayton, P E; Johnson, M L; Celniker, A; Perlman, A J; Alberti, K G; Thorner, M O

    1993-01-01

    To determine if insulin-like growth factor I (IGF-I) inhibits pulsatile growth hormone (GH) secretion in man, recombinant human IGF-I (rhIGF-I) was infused for 6 h at 10 micrograms.kg-1.h-1 during a euglycemic clamp in 10 normal men who were fasted for 32 h to enhance GH secretion. Saline alone was infused during an otherwise identical second admission as a control. As a result of rhIGF-I infusion, total and free IGF-I concentrations increased three- and fourfold, respectively. Mean GH concentrations fell from 6.3 +/- 1.6 to 0.59 +/- 0.07 micrograms/liter after 120 min. GH secretion rates, calculated by a deconvolution algorithm, decreased with a t 1/2 of 16.6 min and remained suppressed thereafter. Suppression of GH secretion rates occurred within 60 min when total and free IGF-I concentrations were 1.6-fold and 2-fold above baseline levels, respectively, and while glucose infusion rates were < 1 mumol.kg-1.min-1. During saline infusion, GH secretion rates remained elevated. Infusion of rhIGF-I decreased the mass of GH secreted per pulse by 84% (P < 0.01) and the number of detectable GH secretory pulses by 32% (P < 0.05). Plasma insulin and glucagon decreased to nearly undetectable levels after 60 min of rhIGF-I. Serum free fatty acids, beta-hydroxybutyrate, and acetoacetate were unaffected during the first 3 h of rhIGF-I but decreased thereafter to 52, 32, and 50% of levels observed during saline. We conclude that fasting-enhanced GH secretion is rapidly suppressed by a low-dose euglycemic infusion of rhIGF-I. This effect of rhIGF-I is likely mediated through IGF-I receptors independently of its insulin-like metabolic actions. PMID:8514857

  13. Pharmacokinetics and Postprandial Glycemic Excursions following Insulin Lispro Delivered by Intradermal Microneedle or Subcutaneous Infusion

    PubMed Central

    McVey, Elaine; Hirsch, Laurence; Sutter, Diane E.; Kapitza, Christoph; Dellweg, Sibylle; Clair, Janina; Rebrin, Kerstin; Judge, Kevin; Pettis, Ronald J.

    2012-01-01

    Background Intradermal (ID) delivery has been shown to accelerate insulin pharmacokinetics (PK). We compared the PK and pharmacodynamic (PD) effects of insulin lispro administered before two daily standardized solid mixed meals (breakfast and lunch), using microneedle-based ID or traditional subcutaneous (SC) delivery. Method The study included 22 subjects with type 1 diabetes in an eight-arm full crossover block design. One arm established each subject’s optimal meal dose. In six additional arms, the optimal, higher, and lower doses (+30%, -30%) were each given ID and SC delivery, in random order. The final arm assessed earlier timing for the ID optimal dose (-12 versus -2 min). The PK/PD data were collected for 6 h following meals. Intravenous basal regular insulin was given throughout, and premeal blood glucose (BG) adjusted to 115 mg/dl. Results The primary end point, postprandial time in range (70–180 mg/dl), showed no route-based differences with a high level of overall BG control for both SC and ID delivery. Secondary insulin PK end points showed more rapid ID availability versus SC across doses and meals (∆Tmax -16 min, ∆T50rising -7 min, ∆T50falling -30 min, all p < .05). Both intrasubject and intersubject variability for ID Tmax were significantly lower. Intradermal delivery showed modest, statistically significant secondary PD differences across doses and meals, generally within 90–120 min postprandially (∆12 mg/dl BG at 90 min, ∆7 mg/dl BGmax, ∆7 mg/dl mean BG 0–2 h, all p < .05). Conclusions This study indicates that ID insulin delivery is superior to SC delivery in speed of systemic availability and PK consistency and may improve postprandial glucose control. PMID:22920798

  14. A continuous [{sup 15}O]H{sub 2}O production and infusion system for PET imaging

    SciTech Connect

    Sajjad, Munawwar; Liow, Jeih-San

    1999-06-10

    A system for continuous production and infusion of [{sup 15}O]H{sub 2}O has been designed for PET cerebral blood flow studies. The injection system consists of a four-port-two-position valve, two Horizon Nxt infusion pumps, and a sterile 50 ml vial. The variation of the production of [{sup 15}O]H{sub 2}O was <1%. The variation of activity delivered measured by scanner counts during the steady state period was <2%.

  15. Infection risk and stability of a continuous 8-h 250 mL rFVIII infusion.

    PubMed

    Lambing, A; Kuriakose, P; Mueller, L M

    2014-03-01

    This study seeks to identify the delivery method of continuous infusion using a 250 cc IV bag via pump, change every 8 h. Additionally, the study will examine the infection risk with the use of 8 h infusions. Ten hemophilia A patients were identified for the study. Each patient received a bolus factorVIII (FVIII) infusion with a pre FVIII level and 1 h post FVIII level to determine recovery levels for optimal dosing. On the day of 8-h continuous infusion, the pt received a bolus VIII (Kogenate FS (™)) for correction to 100% followed by individually calculated continuous infusion (Kogenate FS (™)) FVIII. FVIII levels were drawn from the IV bag and peripherally from the patient in the opposite arm at time points: pre infusion, 1, 2, 3, 4, 5, 6 and 8 h. Additionally, blood cultures were drawn from the IV bag and from the IV tubing at time points pre infusion, 4 and 8 h. Fourteen subjects agreed to participate in the study; 4 failed to follow up, hence 10 subjects were included in the analysis of data; 7 severe, 2 moderate, and 1 mild hemophilia A. Age range was 26-62 years. Ethnic breakdown included 5 African American, 4 Caucasian, 1 Hispanic. With all infusions, the range of FVIII was 65-135% (blood) and 62-200% (bag). After the start of infusion, there were no significant differences noted between the hourly FVIII levels in the subjects and the IV values (P-value range 0.36-0.9). Additionally, given three time points with six cultures per patient, totaling 60 points of cultures drawn for the study, all cultures from the IV bag and patient were negative. The effective delivery method and safety of an 8-h continuous infusion of FVIII (Kogenate FS (™)) has been confirmed. This method can be helpful given that many hospitals may not carry the required mini-pumps, allowing a standard safe delivery of FVIII (Kogenate FS (™)) continuous infusion by available means. PMID:24251950

  16. [Brain edema treatment procedure using continuous controlled infusion of mannitol in neurosurgical patients].

    PubMed

    Taranova, I I; Kokhno, V N

    2010-01-01

    The paper evaluates the efficiency and safety of the developed osmotherapy protocol using controlled continuous infusion of 15% mannitol solution. Two hundred and nine patients with intracranial hypertension (ICH) syndrome of various etiologies had 15% mannitol infusion, the rate of which was determined by clinical criteria. The infusion rate was 50 ml/hr with midline brain structure dislocation of 8 mm or more and major depression of consciousness (a Glasgow coma scale (GCS) score of less than 8) and 25 ml/hr with brain dislocation of 7-mm or less and a GCS score of 8 or higher. The monitoring program was as follows: Block 1 comprised the clinical and instrumental data characterizing the adequacy of brain perfusion (GCS, the magnitude of focal neurological symptoms, ICH, mean blood pressure, computed tomographic dislocation); Block 2 involved the clinical and laboratory data identifying the extracerebral complications of osmotherapy (packed cell volume, plasma osmolarity, urine density, and renal ultrasonography); Block 3 consisted of cerebral oximetry (CO) and Neurotrend. The authors' early proposed integral indicators of OC, such as interhemispheric asymmetry coefficient and hemodynamic conformity index, were used to estimate the adequacy of brain perfusion. In cerebral vasospasm, a Neurotrend microsensor was implanted at 3-cm depth for the direct quantitative determination of pO2, pCO2, pH, and brain temperature. ICH was characterized by natural changes in the CO indicators. In vasospasm, the mean linear blood flow velocity was 245 +/- 14 cm/sec in the basilar arteries, which was attended by low pO2 and metabolic acidosis, as shown by readings. Optimization of artificial ventilation, stabilization of hemodynamics, and the use of postural exposures and osmo diuretics promoted ICH normalization and central perfusion pressure optimization, which was accompanied by the disappearance of tissue hypoxia and acidosis, as suggested by Neurotrend reading. The duration of

  17. Continuous Infusion of 20-Hydroxyecdysone Increased Mass of Triceps Brachii in C57BL/6 Mice

    PubMed Central

    Cheng, Diana M.; Kutzler, Louis W.; Boler, Dustin D.; Drnevich, Jenny; Killefer, John; Lila, Mary Ann

    2012-01-01

    Phytoecdysteroids have been attributed with numerous pharmacological properties in animals, including increasing muscle mass, and 20-hydroxyecdysone (20E) is one of the most abundant phytoecdysteroids produced by plants. In this study, the physiological and gene expression effects of 20E were analyzed in C57BL/6 mice given a continuous infusion of saline or 20E (5 mg/kg/day) for 5 or 15 d using subcutaneously implanted Alzet® osmotic pumps. The masses of the total body, muscle groups and organs were determined. There was a significant increase (p = 0.01) in the mass of triceps brachii in mice treated with 20E for 5 d (115 +/− 8 mg) compared to mice treated with saline for 5 d (88 +/− 3 mg), however, there were no differences in the other measured parameters. To determine potential mechanisms of 20E in skeletal muscle, Illumina’s Mouse Whole Genome-6 v2.0 Expression BeadChips were used to evaluate changes in gene expression of the triceps brachii after 20E infusion. Ingenuity Pathways Analysis was used to identify genes with the most evidence for differential expression, of which, 16 genes involved in the skeletal and muscular system were identified. Overall, the data suggests that 20E does not have potent anabolic properties, however, a muscle-specific increase was observed and genes were identified to provide an explanation for the muscle accretion. PMID:22495969

  18. Administration of high-dose continuous infusion interleukin-2 to patients age 70 or over.

    PubMed

    Quan, Walter; Ramirez, Maria; Taylor, Chris; Quan, Francine; Vinogradov, Mikhail; Walker, Paul

    2005-02-01

    High-dose bolus or continuous infusion interleukin-2-based therapy can cause capillary leak syndrome. Significant cardiovascular/hemodynamic events, including myocardial infarction, hypotension, pulmonary edema, and cardiac arrhythmia, have been described with such therapy. Concern over the toxicity of highdose interleukin-2 (IL-2) therapy has led to some clinicians excluding patients 70 years of age or over. We have treated 15 patients 70 years of age or over having an Eastern Conference Oncology Group (ECOG) performance status of 0 or 1, with therapy based on continuous infusion IL-2 18 MIU/sq m/24 hours for 72 hours. All patients underwent a pretreatment evaluation of cardiac status with a low-level stress or adenosine stress test. Cycles were typically repeated every 3 weeks for 4 cycles, then every 3-4 weeks thereafter. Patients were treated by oncology nurses in either the stem cell transplant (intermediate unit) or the oncology inpatient unit. Patient characteristics were: median age, 72 years (range, 70-83 years); tumor types: melanoma (10), kidney cancer (5); most common sites of disease: lung (11), lymph nodes (6), subcutaneous (3), liver (2); prior therapy included: none (8), outpatient IL-2 (5), other immunotherapy (4). Median number of cycles received: 3 (1-10). Most common toxicities were: fever, rigors, nausea, emesis, hypophosphatemia, and hypomagnesemia. Three patients required the use of dopamine for blood pressure support. Two patients declined further therapy. There were no treatment-related deaths. No patients required endotracheal intubation or transfer to an intensive care unit. One complete and 8 partial responses (60% response rate) have been seen. Responding sites include the lung, lymph node, intact kidney primary, and liver. Median survival has not been reached at over 14 months (range 3+-26+ months). Patients who are 70 years of age and older with an ECOG performance status of 0 or 1 are able to tolerate high-dose continuous infusion IL

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

    PubMed

    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

  20. 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

  1. A wearable optical device for continuous monitoring during neoadjuvant chemotherapy infusions

    NASA Astrophysics Data System (ADS)

    Teng, Fei; Cormier, Timothy; Sauer-Budge, Alexis; Roblyer, Darren M.

    2016-03-01

    We present a new continuous-wave (CW) wearable diffuse optical device aimed at investigating the hemodynamic response of locally advanced breast cancer patients during a patient's first neoadjuvant chemotherapy infusion. The system consists of a flexible substrate that supports an array of surface-mount LED and photodiode pairs (i.e. optodes). Probe performance was evaluated using solid tissue-simulating phantoms. Measurements revealed high SNR (65dB), low source-detector crosstalk (-59 dB), high measurement precision (0.17%), and good thermal stability (0.2% Vrms/°C). A cuff occlusion experiment was performed on the forearm of a healthy volunteer to demonstrate the ability to track rapid hemodynamic changes.

  2. [Effect of the continuous epidural saline infusion for patients with postdural puncture headache after pulmonary resection].

    PubMed

    Katayama, Tatsuya; Hirai, Shinji; Hamanaka, Yoshiharu; Fukui, Takayuki; Itou, Shimon; Hatooka, Shunzou; Mitsudomi, Tetsuya

    2011-11-01

    The dual puncture is one of the diseaseful complications at the induction of the epidural anesthesia, which causes severe symptoms of intracranial hypotension such as headache and nausea. The clinical courses of 3 patients with the dual puncture symptoms after pulmonary resections were retrospectively reviewed, and the effect of the continuous epidural saline infusion treatment (CESI) for the dual puncture was evaluated. Pneumococcal empyema developed in 1 patient who had been treated with conservative management. In contrast, the symptoms of the others who were treated with the CESI were quickly recovered or were effectively prevented. This report strongly suggested that the CESI was convenient and effective treatment for dual punctune symptoms by suppressing the cerebrospinal fluid leakage by elevation of the fluid pressure in the extradural space. PMID:22187867

  3. Transient hyperammonemia related to chemotherapy with continuous infusion of high-dose 5-fluorouracil.

    PubMed

    Liaw, C C; Liaw, S J; Wang, C H; Chiu, M C; Huang, J S

    1993-06-01

    Hyperammonemic encephalopathy has been reported in patients receiving chemotherapy (CT). It is characterized by abrupt alteration in mental status with markedly elevated plasma ammonium levels in the absence of obvious liver disease. This paper reports seven patients who developed transient hyperammonemia during chemotherapy. The regimens all included continuous infusion of high-dose 5-fluorouracil (5-FU). The onset of hyperammonemic encephalopathy was 1.5-4 days after the start of CT. Five cases had infection and six had prerenal azotemia at the time of hyperammonemia. After management, plasma ammonium levels all returned to the normal range within 2 days. Except for one persistent coma, status of consciousness cleared completely. The true mechanism of transient hyperammonemia is unclear. The excess production of ammonium due to metabolites of 5-FU added to precipitating factors such as infection, hypovolemia or constipation may be the explanation for transient hyperammonemia in our study. PMID:8358058

  4. Chronic Continuous Exenatide Infusion Does Not Cause Pancreatic Inflammation and Ductal Hyperplasia in Non-Human Primates

    PubMed Central

    Fiorentino, Teresa Vanessa; Owston, Michael; Abrahamian, Gregory; La Rosa, Stefano; Marando, Alessandro; Perego, Carla; Di Cairano, Eliana S.; Finzi, Giovanna; Capella, Carlo; Sessa, Fausto; Casiraghi, Francesca; Paez, Ana; Adivi, Ashwin; Davalli, Alberto; Fiorina, Paolo; Guardado Mendoza, Rodolfo; Comuzzie, Anthony G.; Sharp, Mark; DeFronzo, Ralph A.; Halff, Glenn; Dick, Edward J.; Folli, Franco

    2016-01-01

    In this study, we aimed to evaluate the effects of exenatide (EXE) treatment on exocrine pancreas of nonhuman primates. To this end, 52 baboons (Papio hamadryas) underwent partial pancreatectomy, followed by continuous infusion of EXE or saline (SAL) for 14 weeks. Histological analysis, immunohistochemistry, Computer Assisted Stereology Toolbox morphometry, and immunofluorescence staining were performed at baseline and after treatment. The EXE treatment did not induce pancreatitis, parenchymal or periductal inflammatory cell accumulation, ductal hyperplasia, or dysplastic lesions/pancreatic intraepithelial neoplasia. At study end, Ki-67–positive (proliferating) acinar cell number did not change, compared with baseline, in either group. Ki-67–positive ductal cells increased after EXE treatment (P = 0.04). However, the change in Ki-67–positive ductal cell number did not differ significantly between the EXE and SAL groups (P = 0.13). M-30–positive (apoptotic) acinar and ductal cell number did not change after SAL or EXE treatment. No changes in ductal density and volume were observed after EXE or SAL. Interestingly, by triple-immunofluorescence staining, we detected c-kit (a marker of cell transdifferentiation) positive ductal cells co-expressing insulin in ducts only in the EXE group at study end, suggesting that EXE may promote the differentiation of ductal cells toward a β-cell phenotype. In conclusion, 14 weeks of EXE treatment did not exert any negative effect on exocrine pancreas, by inducing either pancreatic inflammation or hyperplasia/dysplasia in nonhuman primates. PMID:25447052

  5. Pregnancy in a quadriplegic patient treated with continuous intrathecal baclofen infusion to manage her severe spasticity. Case report.

    PubMed

    Delhaas, E M; Verhagen, J

    1992-07-01

    A report on pregnancy in a quadriplegic patient treated with a high dose of 1000 mcg/24 h continuous intrathecal baclofen infusion using an implanted drug delivery system (Synchromed, Medtronic, USA). Spasticity could be managed up to the 35th week of gestation. However, uterine contractions evoke enormous spastic symptoms which we, even with maximum values of the spasticity scales, could not classify. The recurrence of spasticity was associated with autonomic dysregulation. With continuous epidurally infused bupivacaine (11.25 mg/h) adequate relaxation could be reached and gestation was terminated by a primary caesarean section. A healthy girl was born (2040 g, Apgar 9 and 10). PMID:1508570

  6. First Clinical Experience with a High-Capacity Implantable Infusion Pump for Continuous Intravenous Chemotherapy

    SciTech Connect

    Damascelli, Bruno; Patelli, Gianluigi; Frigerio, Laura F.; Lanocita, Rodolfo; Di Tolla, Giuseppe; Marchiano, Alfonso; Spreafico, Carlo; Garbagnati, Francesco; Bonalumi, Maria G.; Monfardini, Lorenzo; Ticha, Vladimira; Prino, Aurelio

    1999-01-15

    Purpose: To evaluate the efficiency of a new high-capacity pump for systemic venous chemotherapy and to verify the quality of implantation by interventional radiology staff. Methods: A total of 47 infusion pumps with a 60-ml reservoir and variable flow rates (2, 6, 8, or 12 ml/24 hr) were implanted by radiologists in 46 patients with solid tumor metastases requiring treatment with a single, continuously infused cytostatic agent. The reservoir was refilled transcutaneously, usually once weekly. The flow accuracy of the pump was assessed from actual drug delivery recorded on 34 patients over a minimum observation period of 180 days. Results: No early complications occurred in any of the 47 implants in 46 patients. A total of 12 (25.53%) complications occurred between 3 and 24 months after implantation. Seven (14.90%) of these were due to the external design of the pump, while five (10.63%) were related to the central venous catheter. In the 34 patients available for pump evaluation (follow-up of at least 180 days), the system was used for a total of 14,191 days (range 180-911 days, mean 417.38 days), giving an overall complication rate of 0.84 per 1000 days of operation. The mean flow rate accuracy was 90.26%. Conclusion: The new implantable pump showed good flow rate accuracy and reliable operation. The pump-related complications were related to its external design and have now been corrected by appropriate modifications. From a radiologic and surgical viewpoint, the venous implantation procedure is identical to that of conventional vascular access devices and can be performed by radiologists familiar with these techniques. The current limitations lie in the high cost of the pump and, for certain drugs, the short time between refills.

  7. Continuous bilateral infusion of vigabatrin into the subthalamic nucleus: Effects on seizure threshold and GABA metabolism in two rat models.

    PubMed

    Gey, Laura; Gernert, Manuela; Löscher, Wolfgang

    2016-07-01

    The subthalamic nucleus (STN) plays a crucial role as a regulator of basal ganglia outflow but also influences the activity of cortical and limbic structures, so that it is widely used as a therapeutic target in different brain diseases, including epilepsy. In addition to electrical stimulation of the STN, targeted delivery of anti-seizure drugs to the STN may constitute an alternative treatment approach in patients with pharmacoresistant epilepsy. In the present experimental study, we investigated the anti-seizure and adverse effects of chronic infusion of vigabatrin into the STN of rats. Vigabatrin is a clinically approved anti-seizure drug, which acts by increasing brain GABA levels by irreversibly inhibiting GABA-aminotransferase (GABA-T). Based on functional and neurochemical effects of acute STN microinjection, doses for continuous infusion were calculated and administered, using an innovative drug infusion technology. Bilateral infusion of only 10μg/day vigabatrin over 3weeks into the STN resulted in an almost complete inhibition of GABA-T and 4-fold increase in GABA in the target region, which was associated with a significant increase in seizure threshold, determined once weekly by i.v. infusion of pentylenetetrazole (PTZ). Lower doses or unilateral infusion were less effective, both on PTZ seizures and on kindled seizures. Bilateral infusion into substantia nigra pars reticulata was less effective and more toxic than STN infusion. In part of the rats, tolerance to the anti-seizure effect developed. The data demonstrate that chronic administration of very low, nontoxic doses of vigabatrin into STN is an effective means of increasing local GABA concentrations and seizure threshold. PMID:26976738

  8. Study on toxicity of danshensu in beagle dogs after 3-month continuous intravenous infusion.

    PubMed

    Li, Guisheng; Gao, Yonglin; Li, Shenjun; Li, Chunmei; Zhu, Xiaoyin; Li, Min; Liu, Zhifeng

    2009-09-01

    Danshensu (3-(3,4-dihydroxyphenyl) lactic acid), a natural phenolic acid, is isolated from root of Salvia miltiorrhiza, and is widely used as a traditional Chinese medicine for treatment of various cardiovascular diseases. In the present study, toxicity of danshensu was evaluated in male and female dogs after 3-month continuous intravenous infusion. Beagle dogs were treated with danshensu at doses of 17, 50, and 150 mg/kg/day, and observed for 90 days followed by recovery periods. Measurements included clinical observations, body weight, food consumption, temperature, electro-cardiography (EGC), hematology, blood chemistry, urinalysis, gross necropsy, organ weight, and histopathology. No significant adverse effects on these parameters were observed. The only treatment-related finding was a hard knot at injection site observed in the 150 mg/kg group after 2-3 weeks continuous administration, and returned to normal after 3-4 days withdrawal. From these results, it might be concluded that danshensu did not produce any significant cumulative toxicity at the doses administered, as reflected by the various parameters investigated. PMID:19778246

  9. Continuous infusion of 5-fluorouracil with alpha 2b interferon for advanced colorectal carcinoma.

    PubMed Central

    Ferguson, J. E.; Hulse, P.; Lorigan, P.; Jayson, G.; Scarffe, J. H.

    1995-01-01

    Thirty patients with symptomatic colorectal carcinoma were commenced on treatment with 5-fluorouracil (2.5 g week-1) administered by continuous intravenous infusion and alpha 2b interferon (3 x 10(6) U s.c. three times a week). Six out of 30 patients (20%) achieved a partial response. Three patients (10%) had stable disease and 21 patients (70%) progressed on treatment. Twenty patients (67%) completed ten or more weeks of treatment. In nine patients, treatment was withdrawn after 2-9 weeks because of disease progression or death. One patient's treatment was interrupted by emergency surgery. The median survival for all patients was 210 days (7 months). The principal side-effects were oral mucositis (12/30 patients), nausea (8/30 patients) and transient diarrhoea (4/30 patients), and initial constitutional symptoms due to alpha 2b interferon. The combination of low-dose continuous infusional 5-fluorouracil and low-dose alpha 2b interferon is well tolerated but has no obvious advantage over alternative infusional regimens using 5-fluorouracil as a single agent. PMID:7599051

  10. Controlled Study of the Effects of Continuous Intrathecal Baclofen Infusion in Non-Ambulant Children with Cerebral Palsy

    ERIC Educational Resources Information Center

    Morton, Richard E.; Gray, Natalie; Vloeberghs, Michael

    2011-01-01

    Aim: To measure changes in children with severe spastic cerebral palsy (CP) after continuous intrathecal baclofen (ITB) infusion over 18 months and to compare the results with those of a comparison group awaiting treatment. Method: Thirty-eight children with severe spastic CP considered suitable for ITB were assessed when first seen, just before…

  11. Continuous infusion interleukin-2 and antihistamines in melanoma: a retrospective review showing activity of this combination.

    PubMed

    Evangelista-Dean, Maria; Khan, Nawazish; Quan, Walter

    2004-12-01

    A recent randomized trial suggests that there may be an advantage in terms of survival with the combination of histamine and subcutaneous interleukin-2 (IL-2), compared to IL-2 alone. It has been postulated, then, that antihistamines may actually be antagonistic to IL-2 and, therefore, interfere with its antitumor activity. Because antihistamines such as cimetidine and ranitidine are commonly used as prophylaxis against gastrointestinal toxicity commonly seen with IL-2, and, because antihistamines may increase natural killer cell activity, it is reasonable to examine the response rate for this combination. An OVID Medline literature search between 1985 and 2003 was done. Continuous infusion (CIV) interleukin- 2 was used as the reference therapy because of the relatively constant IL-2 levels generated by this approach. Included studies were those in which either cimetidine, ranitidine, or famotidine were regularly scheduled and administered concurrently with IL-2, typically for gastrointestinal ulcer prophylaxis. Six (6) studies were identified. A total of 21 patients responded to therapy. Total response rate was 11%, with a 95% Confidence Interval: 7-17%. Four (4) complete responses were noted. Complete response rate was 2%, with a 95% Confidence Interval: 1-6%. These response rates are consistent with previously noted IL-2 response rates. In this retrospective review of CIV IL-2 and antihistamines, this combination appears to be active in melanoma. There appears to be no deleterious effect of routine antihistamine on the CIV IL-2 response rate. PMID:15665623

  12. [Continuous intrathecal infusion of baclofen. A new therapeutic method for spasticity].

    PubMed

    Berg-Johnsen, J; Røste, G K; Solgaard, T; Lundar, T

    1998-09-10

    Intrathecal administration of baclofen is now generally accepted as a powerful treatment of spasticity caused by spinal lesions. 35 patients with severe spasticity, 29 of spinal origin and six of supraspinal origin resistant to conservative treatment, had a programmable pump (Synchromed, Medtronic) for continuous intrathecal baclofen infusion implanted. The patients were followed-up for an average of 29 months (0-68). The initial effect of the treatment was positive for all patients; spasms were less frequent, there was remission of pain caused by cramps, and in some cases improved ambulation. In five patients, however, the pump was later removed: in two patients the pump ceased to be effective, two patients became infected, and one experienced multiple catheter problems. Problems with the catheter was the most common complication experienced, and this was seen in nine patients. Three patients died of the underlying disease. The majority of patients became accommodated to intrathecal baclofen and it was necessary to administer increasingly larger doses to maintain the clinical effect. Long-term control of spinal spasticity by intrathecal baclofen can be achieved in most patients, but close follow-up is necessary for assessing efficacy and refilling the pump. PMID:9772811

  13. Use of continuous local anesthetic infusion in the management of postoperative split-thickness skin graft donor site pain.

    PubMed

    Hernandez, Jorge L Reguero; Savetamal, Alisa; Crombie, Roselle E; Cholewczynski, Walter; Atweh, Nabil; Possenti, Paul; Schulz, John T

    2013-01-01

    Donor sites from split-thickness skin grafts (STSG) impose significant pain on patients in the early postoperative period. We report the use of continuous local anesthetic infusion as a method for the management of postoperative STSG donor site pain. Patients undergoing single or dual, adjacent STSG harvest from the thigh (eight patients) or back (one patient) were included in this study. Immediately after STSG harvest, subcutaneous catheters were placed for continuous infusion of local anesthetic. Daily donor site-specific pain severity scores were prospectively recorded in nine patients receiving local anesthetic infusion. Patient characteristics, technical aspects, and postoperative complications were identified in the study. The thigh was the anatomic location chosen for most donor sites. A single catheter was placed for donor sites limited to 4 inches in width or less. A dual catheter system was used for those wider than 4 inches. An elastomeric pump delivered continuously a total of 4 ml/hr of a solution of 0.5% bupivacaine. The average anesthetic infusion duration was 3.1 days. A substantial decrease in worst, least, and average donor site pain scores was found from the first 24 hours to the second postoperative day in our patients, a treatment trend that continued through postoperative day 3. One patient developed minor anesthetic leakage from the catheter insertion site; and in three cases, accidental dislodgement of the catheters occurred. There were no cases of donor site secondary infection. All donor sites were completely epithelialized at 1-month follow-up. Continuous local anesthetic infusion is technically feasible and may represent an option for postoperative donor site pain control after STSG harvesting. Relative cost-benefit of the technique remains to be determined. PMID:23271060

  14. New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients.

    PubMed

    Cristallini, Stefano; Hites, Maya; Kabtouri, Hakim; Roberts, Jason A; Beumier, Marjorie; Cotton, Frederic; Lipman, Jeffrey; Jacobs, Frédérique; Vincent, Jean-Louis; Creteur, Jacques; Taccone, Fabio Silvio

    2016-08-01

    Despite the development of new agents with activity against Gram-positive bacteria, vancomycin remains one of the primary antibiotics for critically ill septic patients. Because sepsis can alter antimicrobial pharmacokinetics, the development of an appropriate dosing strategy to provide adequate concentrations is crucial. The aim of this study was to prospectively validate a new dosing regimen of vancomycin given by continuous infusion (CI) to septic patients. We included all adult septic patients admitted to a mixed intensive care unit (ICU) between January 2012 and May 2013, who were treated with a new vancomycin CI regimen consisting of a loading dose of 35 mg/kg of body weight given as a 4-h infusion, followed by a daily CI dose adapted to creatinine clearance (CrCL), as estimated by the Cockcroft-Gault formula (median dose, 2,112 [1,500 to 2,838] mg). Vancomycin concentrations were measured at the end of the loading dose (T1), at 12 h (T2), at 24 h (T3), and the day after the start of therapy (T4). Vancomycin concentrations of 20 to 30 mg/liter at T2, T3, and T4 were considered adequate. A total of 107 patients (72% male) were included. Median age, weight, and CrCL were 59 (interquartile range [IQR], 48 to 71) years, 75 (IQR, 65 to 85) kg, and 94 (IQR, 56 to 140) ml/min, respectively. Vancomycin concentrations were 44 (IQR, 37 to 49), 25 (IQR, 21 to 32), 22 (IQR, 19 to 28), and 26 (IQR, 22 to 29) mg/liter at T1, T2, T3, and T4, respectively. Concentrations were adequate in 56% (60/107) of patients at T2, in 54% (57/105) at T3, and in 73% (41/56) at T4. This vancomycin regimen permitted rapid attainment of target concentrations in serum for most patients. Concentrations were insufficient in only 16% of patients at 12 h of treatment. PMID:27216073

  15. Continuous infusion of antibiotics in the critically ill: The new holy grail for beta-lactams and vancomycin?

    PubMed Central

    2012-01-01

    The alarming global rise of antimicrobial resistance combined with the lack of new antimicrobial agents has led to a renewed interest in optimization of our current antibiotics. Continuous infusion (CI) of time-dependent antibiotics has certain theoretical advantages toward efficacy based on pharmacokinetic/pharmacodynamic principles. We reviewed the available clinical studies concerning continuous infusion of beta-lactam antibiotics and vancomycin in critically ill patients. We conclude that CI of beta-lactam antibiotics is not necessarily more advantageous for all patients. Continuous infusion is only likely to have clinical benefits in subpopulations of patients where intermittent infusion is unable to achieve an adequate time above the minimal inhibitory concentration (T > MIC). For example, in patients with infections caused by organisms with elevated MICs, patients with altered pharmacokinetics (such as the critically ill) and possibly also immunocompromised patients. For vancomycin CI can be chosen, not always for better clinical efficacy, but because it is practical, cheaper, associated with less AUC24h (area under the curve >24 h)-variability, and easier to monitor. PMID:22747633

  16. Continuous nutrient administration decreases insulin sensitivity in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously showed that chronic TPN compared to intermittent feeding of a formula results in hepatic insulin resistance and steatosis in neonatal pigs. We hypothesized that the route of feeding (IV vs enteral) rather than the nature of the diet (elemental vs polymeric) or the feeding regimen (cont...

  17. Subcutaneous insulin substitution in insulin-dependent diabetes mellitus. Pharmacokinetic and pharmacodynamic studies.

    PubMed

    Olsson, P O

    1987-01-01

    Determination of free and total insulin with radioimmunoassay, after precipitation of endogenous insulin antibodies with polyethylene glycol, was evaluated. Insulin substitution in insulin-dependent diabetic patients was investigated, embracing the 24 h free insulin and glucose profiles with different regimens, the miscibility of insulin preparations, the overnight metabolic control, and bolus doses of different size with infusion pumps. In the free and total insulin assay precipitation of immunoglobulins with polyethylene glycol was almost complete and the recovery was high. Compared to immediately precipitated and assayed plasma samples at 37 degrees C, free insulin slightly decreased in immediately processed serum (20 degrees C), and also in plasma after 3 h at 20 degrees C. In stored (-20 degrees C) unprecipitated plasma samples free insulin increased after 4 weeks and also in serum samples after 26 weeks, whereas stored PEG-supernates were stable. In healthy controls a low basal insulin was found, increasing about tenfold postprandially. No morning rise in free insulin or glucose was found. The 24 h free insulin profile was strikingly unphysiological with 1 or 2 dose regimens; there was preprandial and nocturnal hyperinsulinaemia but absence of meal-related free insulin peaks. A considerable glucose rise was found after breakfast. Intensive regimens with conventional injections or infusion pumps, gave 24 h free insulin profiles that were similar to the physiological. However, the prandial peaks were retarded; and hyperinsulinaemia was shown with infusion pumps during daytime. An immediate loss of regular insulin was demonstrated after mixture with semisynthetic human lente insulin in vitro and in vivo, but not after mixture with biosynthetic human NPH insulin. The morning glucose control was similar with a bedtime injection of intermediate-acting insulin or continuous subcutaneous insulin infusion, but less hyperinsulinaemia overnight was found with the

  18. Alternative Devices for Taking Insulin

    MedlinePlus

    ... pumps contain enough insulin for several days. An infusion set carries insulin from the pump to the ... tube or needle inserted under the skin. Disposable infusion sets are used with insulin pumps to deliver ...

  19. Real-time estimation of plasma insulin concentration from continuous glucose monitor measurements.

    PubMed

    de Pereda, Diego; Romero-Vivo, Sergio; Ricarte, Beatriz; Rossetti, Paolo; Ampudia-Blasco, Francisco Javier; Bondia, Jorge

    2016-01-01

    Continuous glucose monitors can measure interstitial glucose concentration in real time for closed-loop glucose control systems, known as artificial pancreas. These control systems use an insulin feedback to maintain plasma glucose concentration within a narrow and safe range, and thus to avoid health complications. As it is not possible to measure plasma insulin concentration in real time, insulin models have been used in literature to estimate them. Nevertheless, the significant inter- and intra-patient variability of insulin absorption jeopardizes the accuracy of these estimations. In order to reduce these limitations, our objective is to perform a real-time estimation of plasma insulin concentration from continuous glucose monitoring (CGM). Hovorka's glucose-insulin model has been incorporated in an extended Kalman filter in which different selected time-variant model parameters have been considered as extended states. The observability of the original Hovorka's model and of several extended models has been evaluated by their Lie derivatives. We have evaluated this methodology with an in-silico study with 100 patients with Type 1 diabetes during 25 h. Furthermore, it has been also validated using clinical data from 12 insulin pump patients with Type 1 diabetes who underwent four mixed meal studies. Real-time insulin estimations have been compared to plasma insulin measurements to assess performance showing the validity of the methodology here used in comparison with that formerly used for insulin models. Hence, real-time estimations for plasma insulin concentration based on subcutaneous glucose monitoring can be beneficial for increasing the efficiency of control algorithms for the artificial pancreas. PMID:26343364

  20. Plasma nitrate plus nitrite changes during continuous intravenous infusion interleukin 2.

    PubMed Central

    Citterio, G.; Pellegatta, F.; Lucca, G. D.; Fragasso, G.; Scaglietti, U.; Pini, D.; Fortis, C.; Tresoldi, M.; Rugarli, C.

    1996-01-01

    Nitric oxide (NO), a biologically active mediator generated in many cell types by the enzyme NO synthase, may play an important role in cardiovascular toxicity that is frequently observed in cancer patients during intravenous (i.v.) interleukin 2 (IL-2) therapy. The induction of NO synthase and the production of NO seem to be involved in the pathogenesis of the vascular leakage syndrome, as well as in the regulation of myocardial contractility. In the present study, we evaluated the pattern of plasmatic NO changes during multiple cycles of continuous i.v. infusion (CIVI) of IL-2 in ten advanced cancer patients (five males, five females, median age 59 years, range 33-67 years; eight affected by renal cell cancer and two affected by malignant melanoma). The patients received IL-2 at 18 MIU m-2 day-1 (14 cycles) or 9 MIU m-2 day-1 (seven cycles) for 96 h, repeated every 3 weeks. Interferon alpha (IFN alpha) was also administered subcutaneously (s.c) during the 3 week interval between IL-2 cycles. For each cycle, plasma samples were collected before treatment (t0), 24 h (t1), 48 h (t2), 72 h (t3) and 96 h (t4) after the start of IL-2 infusion, and 24 h after the end of the cycle. NO concentration was determined spectrophotometrically by measuring the accumulation of both nitrite and nitrate (after reduction to nitrite). The following observations may be drawn from data analysis: (1) plasma nitrate + nitrite significantly raised during treatment (P = 0.0226 for t0 vs t3), but statistical significance was retained only when cycles administered with IL-2 18 MIU m-2 day-1 are considered (P = 0.0329 for t0 vs t3; P = 0.0354 for t0 vs t2 vs t4) (dose-dependent pattern); (2) during subsequent cycles a significant trend toward a progressive increase of plasma nitrate + nitrite levels, with increasing cumulative dose of IL-2, was observed (linear regression coefficient r = 0.62, P = 0.0141 for t0; r = 0.80, P = 0.0003 for t1; r = 0.62, P = 0.013 for t2; r = 0.69, P = 0.045 for

  1. A Continuous Infusion Fascia Iliaca Compartment Block in Hip Fracture Patients: A Pilot Study

    PubMed Central

    Dulaney-Cripe, Elizabeth; Hadaway, Scott; Bauman, Ryan; Trame, Cathy; Smith, Carole; Sillaman, Becky; Laughlin, Richard

    2012-01-01

    Background Hip fractures account for 350,000 fractures annually and the projected incidence is expected to exceed 6.3 million by 2050. As the number of hip fractures continues to increase as a result of the aging American population, the importance of limiting and preventing complications is magnified. Methods This study demonstrated the clinical effects of a continuous fascia iliaca compartment block placed pre-operatively when combined with a comprehensive pain protocol. All patients who presented to our institution with a hip fracture were given the option of having a continuous fascia iliaca compartment block for pain control versus usual pain management (non-opioids, opioids, and ice therapy). The block was monitored by the pain service until the day of discharge from the hospital. Data was collected regarding mean pain scores, average length of stay and opioid medication use. Results There were eighteen males and twenty four females. The pain score on post-operative day zero was reduced from a 2010 annual average of 4.1 to 1.7 in the pilot study group on the visual analog score. On post-operative day one, the 2010 annual average was 2.9 compared to 1.4 in the pilot study group. The length of stay was decreased from the 2010 annual average of 5.9 days to 4.8 days in the pilot study group. The patients used an average of 18mg of morphine equivalent medications during the average infusion time of 40.7 hours. There were no falls or infections noted within our pilot study group. Conclusions Overall, it has been noticed that the reduction in opioid usage in this elderly patient population, with an average age of seventy five years, has produced alert and mobile patients often as early as post-operative day one. The length of stay has decreased along with the average pain score in the pilot sample of forty two patients. Keywords Hip fracture; Fascia Iliaca Compartment Block; Pain Score PMID:22383926

  2. Comparison of continuous epidural infusion and programmed intermittent epidural bolus in labor analgesia

    PubMed Central

    Lin, Yunan; Li, Qiang; Liu, Jinlu; Yang, Ruimin; Liu, Jingchen

    2016-01-01

    Background This study aims to investigate differences between continuous epidural infusion (CEI) and programmed intermittent epidural bolus (IEB) analgesia for the Chinese parturients undergoing spontaneous delivery and to approach their safety to parturients and neonates. Methods Two hundred healthy American Society of Anesthesiologists class I or II, term (≥37 weeks’ gestation), nulliparous women who requested analgesia for labor were recruited. Epidural analgesia was initiated with a solution of 0.15% ropivacaine 10 mL and maintained with 0.1% ropivacaine mixed with sufentanil 0.3 μg/mL by CEI at a rate of 5 mL/h combined with a patient-controlled epidural analgesia (PCEA) bolus of 5 mL of ropivacaine sufentanil mixture or IEB of 5 mL of ropivacaine sufentanil mixture combined with a PCEA bolus of 5 mL of ropivacaine sufentanil mixture. The lockout interval was 20 minutes in each arm between the CEI and the IEB group. After 20 minutes of first dosage, visual analog scale (VAS) score was obtained every 60 minutes. The maternal and fetal outcome and total consumption of analgesic solution were compared. Results There was no difference in demographic characteristics, duration of first and second stages, delivery methods, sensory block, fetal Apgar scores, and the maternal outcomes between the CEI and IEB groups. There was a significant difference in VAS scores and epidural ropivacaine total consumption between the two groups (IEB vs CEI: 51.27±9.61 vs 70.44±12.78 mg, P<0.01). Conclusion The use of programmed IEB mixed with PCEA improved labor analgesia compared to CEI mixed with PCEA, which could act as maintenance mode for epidural labor analgesia. PMID:27471390

  3. Continuous regional arterial infusion for acute pancreatitis: a propensity score analysis using a nationwide administrative database

    PubMed Central

    2013-01-01

    Introduction Although continuous regional arterial infusion (CRAI) of a protease inhibitor and an antibiotic may be effective in patients with severe acute pancreatitis, CRAI has not yet been validated in large patient populations. We therefore evaluated the effectiveness of CRAI based on data from a national administrative database covering 1,032 Japanese hospitals. Methods In-hospital mortality, length of stay and costs were compared in the CRAI and non-CRAI groups, using propensity score analysis to adjust for treatment selection bias. Results A total of 17,415 eligible patients with acute pancreatitis were identified between 1 July and 30 September 2011, including 287 (1.6%) patients who underwent CRAI. One-to-one propensity-score matching generated 207 pairs with well-balanced baseline characteristics. In-hospital mortality rates were similar in the CRAI and non-CRAI groups (7.7% vs. 8.7%; odds ratio, 0.88; 95% confidence interval, 0.44–1.78, P = 0.720). CRAI was associated with significantly longer median hospital stay (29 vs. 18 days, P < 0.001), significantly higher median total cost (21,800 vs. 12,600 United States dollars, P < 0.001), and a higher rate of interventions for infectious complications, such as endoscopic/surgical necrosectomy or percutaneous drainage (2.9% vs. 0.5%, P = 0.061). Conclusions CRAI was not effective in reducing in-hospital mortality rate in patients with acute pancreatitis, but was associated with longer hospital stay and higher costs. Randomized controlled trials in large numbers of patients are required to further evaluate CRAI for this indication. PMID:24088324

  4. Continuous subcutaneous infusion of glucagon by portable pump in non beta cell tumor hypoglycemia.

    PubMed

    Houlbert, D; Altman, J J; Lageron, A; Capeau, J; Dahan, R; Friedberg, G; Wassef, M; Poffenbarger, P L; Segrestaa, J M

    1985-04-01

    Subcutaneous infusion of glucagon by portable pump appears to give very effective symptomatic relief from non beta cell tumor hypoglycemia when surgery, radiotherapy and chemotherapy are impossible or ineffective. This mode of glucagon administration was proposed in a patient who had severe nocturnal hypoglycemic attacks. The aim of the study was to specify the modes of utilization and to test the efficiency and the tolerance of this treatment. Glucagon was infused at 400 micrograms/h during every 12 hour night. Because of the hepatic action of glucagon it is very important to use this treatment with an adequate diet and to stop the infusion during the day to reconstitute the glycogen overload. This mode of glucagon administration was very effective in over 6 months of use and well tolerated. PMID:4007224

  5. Nursing care of patients receiving high-dose, continuous-infusion interleukin-2 with pulse dose and famotidine.

    PubMed

    Tyre, Charley Cowan; Quan, Walter

    2007-08-01

    High-dose, continuous-infusion interleukin-2 (IL-2) followed by pulse dose and concurrent administration of famotidine has demonstrated response rates of 64% and 33% in patients with metastatic melanoma and metastatic renal cell carcinoma, respectively. Currently, no information is available concerning the nursing care of patients receiving that IL-2 regimen. Given the high response rates of patients on the treatment, attention by the nursing profession is warranted. Effective nursing care of patients receiving IL-2 is essential to the regimen's success. Recognition and prompt treatment of common side effects lead to better patient outcomes. This article provides nurses with an overview of the treatment regimen, expected side effects, psycho-social considerations, and discharge instructions for patients receiving continuous-infusion plus pulse IL-2 and famotidine. PMID:17723964

  6. Continuous intestinal infusion of levodopa/carbidopa in advanced Parkinson's disease: efficacy, safety and patient selection.

    PubMed

    Abbruzzese, Giovanni; Barone, Paolo; Bonuccelli, Ubaldo; Lopiano, Leonardo; Antonini, Angelo

    2012-01-01

    Long-term oral therapy with levodopa is associated with the development of motor fluctuations and dyskinesia in a large percentage of patients with Parkinson's disease (PD). Motor complications are associated with a number of non-motor symptoms and have a negative impact on disability and quality of life. There are three therapeutic options available for the management of patients at this advanced stage: high frequency deep brain stimulation, continuous subcutaneous infusion of apomorphine, and continuous intestinal infusion of levodopa/carbidopa. On the basis of published data and in consideration of the risk-benefit profile of current therapeutic strategies, we here propose an algorithm to help clinicians select the most suitable treatment option for patients with advanced PD. PMID:23402675

  7. Oxalate Nephropathy After Continuous Infusion of High-Dose Vitamin C as an Adjunct to Burn Resuscitation

    PubMed Central

    Pamplin, Jeremy; Studer, Lynette; Hughes, Rhome L.; King, Booker T.; Graybill, John C.; Chung, Kevin K.

    2016-01-01

    Fluid resuscitation is the foundation of management in burn patients and is the topic of considerable research. One adjunct in burn resuscitation is continuous, high-dose vitamin C (ascorbic acid) infusion, which may reduce fluid requirements and thus decrease the risk for over resuscitation. Research in preclinical studies and clinical trials has shown continuous infusions of high-dose vitamin C to be beneficial with decrease in resuscitative volumes and limited adverse effects. However, high-dose and low-dose vitamin C supplementation has been shown to cause secondary calcium oxalate nephropathy, worsen acute kidney injury, and delay renal recovery in non-burn patients. To the best of our knowledge, the authors present the first case series in burn patients in whom calcium oxalate nephropathy has been identified after high-dose vitamin C therapy. PMID:25812044

  8. Oxalate Nephropathy After Continuous Infusion of High-Dose Vitamin C as an Adjunct to Burn Resuscitation.

    PubMed

    Buehner, Michelle; Pamplin, Jeremy; Studer, Lynette; Hughes, Rhome L; King, Booker T; Graybill, John C; Chung, Kevin K

    2016-01-01

    Fluid resuscitation is the foundation of management in burn patients and is the topic of considerable research. One adjunct in burn resuscitation is continuous, high-dose vitamin C (ascorbic acid) infusion, which may reduce fluid requirements and thus decrease the risk for over resuscitation. Research in preclinical studies and clinical trials has shown continuous infusions of high-dose vitamin C to be beneficial with decrease in resuscitative volumes and limited adverse effects. However, high-dose and low-dose vitamin C supplementation has been shown to cause secondary calcium oxalate nephropathy, worsen acute kidney injury, and delay renal recovery in non-burn patients. To the best of our knowledge, the authors present the first case series in burn patients in whom calcium oxalate nephropathy has been identified after high-dose vitamin C therapy. PMID:25812044

  9. [Insulin therapy for type 1 diabetes mellitus: past and present].

    PubMed

    Pires, Antonio Carlos; Chacra, Antonio Roberto

    2008-03-01

    The discovery of insulin can be considered the milestone of diabetes mellitus history and a great achievement for its treatment. The first insulin available was the regular. Afterwards, Hagedorn added the protamine to the insulin, thus, creating the NPH insulin. In the 1950s an insulin free of protamine was synthesized: the lente insulin. With the advent of molecular biology, synthetic human insulin was synthesized using recombinant DNA technology. Most recently several types of insulin analogues were available, providing the patients with better metabolic control. Type 1 diabetes mellitus treatment includes plain substitution and individualization for short-acting plus long-acting insulin according to the physician's assistance, besides regular practice of physical activities and diet orientations. In type 1 diabetes mellitus the insulin of low variability is the best choice since basal/bolus insulin therapy or continuous subcutaneous insulin infusion pump can mimetize the physiological release of insulin by beta cells. PMID:18438537

  10. 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

  11. Efficacy of Continuous S(+)-Ketamine Infusion for Postoperative Pain Control: A Randomized Placebo-Controlled Trial

    PubMed Central

    Miziara, Luiz Eduardo de Paula Gomes; Simoni, Ricardo Francisco; Esteves, Luís Otávio; Cangiani, Luis Henrique; Grillo-Filho, Gil Fernando Ribeiro; Paula, Anderson Garcia Lima e

    2016-01-01

    Aim. A double-blind, randomized, placebo-controlled trial was designed to evaluate the efficacy of continuous intraoperative infusion of S(+)-ketamine under intravenous anesthesia with target-controlled infusion of remifentanil and propofol for postoperative pain control. Methods. Forty-eight patients undergoing laparoscopic cholecystectomy were assigned to receive continuous S(+)-ketamine infusion at a rate of 0.3 mg·kg−1·h−1 (n = 24, intervention group) or an equivalent volume of saline at the same rate (n = 24, placebo group). The same target-controlled intravenous anesthesia was induced in both groups. Pain was assessed using a 0 to 10 verbal numeric rating scale during the first 12 postoperative hours. Pain scores and morphine consumption were recorded in the postanesthesia care unit (PACU) and at 4 and 12 hours after surgery. Results. Pain scores were lower in the intervention group at all time points. Morphine consumption did not differ significantly between groups during PACU stay, but it was significantly lower in the intervention group at each time point after PACU discharge (P = 0.0061). At 12 hours after surgery, cumulative morphine consumption was also lower in the intervention group (5.200 ± 2.707) than in the placebo group (7.525 ± 1.872). Conclusions. Continuous S(+)-ketamine infusion during laparoscopic cholecystectomy under target-controlled intravenous anesthesia provided better postoperative pain control than placebo, reducing morphine requirement. Trial Registration. This trial is registered with ClinicalTrials.gov NCT02421913. PMID:26949390

  12. Efficacy of Continuous S(+)-Ketamine Infusion for Postoperative Pain Control: A Randomized Placebo-Controlled Trial.

    PubMed

    Miziara, Luiz Eduardo de Paula Gomes; Simoni, Ricardo Francisco; Esteves, Luís Otávio; Cangiani, Luis Henrique; Grillo-Filho, Gil Fernando Ribeiro; Paula, Anderson Garcia Lima E

    2016-01-01

    Aim. A double-blind, randomized, placebo-controlled trial was designed to evaluate the efficacy of continuous intraoperative infusion of S(+)-ketamine under intravenous anesthesia with target-controlled infusion of remifentanil and propofol for postoperative pain control. Methods. Forty-eight patients undergoing laparoscopic cholecystectomy were assigned to receive continuous S(+)-ketamine infusion at a rate of 0.3 mg·kg(-1)·h(-1) (n = 24, intervention group) or an equivalent volume of saline at the same rate (n = 24, placebo group). The same target-controlled intravenous anesthesia was induced in both groups. Pain was assessed using a 0 to 10 verbal numeric rating scale during the first 12 postoperative hours. Pain scores and morphine consumption were recorded in the postanesthesia care unit (PACU) and at 4 and 12 hours after surgery. Results. Pain scores were lower in the intervention group at all time points. Morphine consumption did not differ significantly between groups during PACU stay, but it was significantly lower in the intervention group at each time point after PACU discharge (P = 0.0061). At 12 hours after surgery, cumulative morphine consumption was also lower in the intervention group (5.200 ± 2.707) than in the placebo group (7.525 ± 1.872). Conclusions. Continuous S(+)-ketamine infusion during laparoscopic cholecystectomy under target-controlled intravenous anesthesia provided better postoperative pain control than placebo, reducing morphine requirement. Trial Registration. This trial is registered with ClinicalTrials.gov NCT02421913. PMID:26949390

  13. Retrospective Review of Critically Ill Patients Experiencing Alcohol Withdrawal: Dexmedetomidine Versus Propofol and/or Lorazepam Continuous Infusions

    PubMed Central

    Ludtke, Kimberly A.; Yount, Natalie L.; Gerkin, Richard D.

    2015-01-01

    Abstract Background: Alcohol withdrawal symptoms can be difficult to manage and may lead to an intensive care unit (ICU) admission. Patients experiencing severe alcohol withdrawal often require high doses of sedatives, which can lead to respiratory depression and the need for endotracheal intubation. Dexmedetomidine, an alpha-2 adrenoreceptor agonist, provides adequate sedation with little effect on respiratory function when compared to other sedatives. Objective: To evaluate sedation with a continuous infusion of dexmedetomidine versus propofol and/or lorazepam in critically ill patients experiencing alcohol withdrawal. Methods: A retrospective chart review was conducted on ICU admissions between March 2002 and April 2009 for alcohol withdrawal patients who necessitated treatment with a continuous infusion of dexmedetomidine, propofol, and/or lorazepam. Primary outcomes included the incidence of mechanical ventilation, length of mechanical ventilation (if applicable), and ICU and hospital length of stay. Results: Fifteen patients were treated with a continuous infusion of dexmedetomidine, and 17 were treated with an infusion of propofol and/or lorazepam. Two patients (13.3%) required intubation and mechanical ventilation in the dexmedetomidine group versus 10 (58.8%) in the propofol and/or lorazepam group (P = .006). Length of stay in the ICU was 53 hours for patients treated with dexmedetomidine versus 114.9 hours in the propofol and/or lorazepam group (P = .016). Hospital length of stay was less for the dexmedetomidine group, 135.8 hours versus 241.1 hours in the propofol and/or lorazepam group (P = .008). Conclusions: Dexmedetomidine use was associated with a decrease in the incidence of endotracheal intubation when used to sedate patients experiencing alcohol withdrawal. Patients transferred to a lower level of care faster and were discharged from the hospital sooner when treated with dexmedetomidine. PMID:26405310

  14. Safety of 96-hour incision-site continuous infusion of ropivacaine for postoperative analgesia after bowel cancer resection.

    PubMed

    Corso, Olivia H; Morris, Raymond G; Hewett, Peter J; Karatassas, Alex

    2007-02-01

    The aim of this study was to examine the safety of ropivacaine given to patients as a continuous infusion [0.2% (2 mg/mL), 5 mL/h for 96 hours] into a right lateral transverse incision using a portable elastomeric infusion pump after colon cancer resection. Blood samples were collected throughout the infusion and up to 12 hours after infusion and were analyzed by high-performance liquid chromatography (HPLC) for total and unbound ropivacaine concentrations in plasma. Alpha1 acid glycoprotein (AAG) concentrations were measured at 0 and 48 hours to assess possible changes in ropivacaine protein binding after surgery. Postoperative pain control was assessed using 12 hour visual analog scale (VAS) scores. Patient-controlled analgesia (PCA) using fentanyl was freely available in parallel for breakthrough pain, with usage and consumption compared with a historical cohort. The mean +/- SD Cmax total plasma ropivacaine concentration (n = 5) from 12 hours to the end of the infusion was 4.5 +/- 2.6 mg/L, comparable with the previously published threshold for CNS toxicity in the most sensitive patient studied (3.4 mg/L). However, the corresponding maximum unbound ropivacaine concentration (ie, the pharmacologically active moiety) of 0.07 +/- 0.01 mg/L ranged from four- to sevenfold below the reported toxicity threshold (0.34 mg/L). The apparently greater safety margin seen with unbound ropivacaine may have resulted from a significant increase (mean 63%, P < 0.05) in AAG concentrations measured at 48 hours after surgery. This reduction resulted from the known AAG reaction after surgical intervention, resulting in a reducing unbound ropivacaine fraction throughout the 96 hour infusion in all patients. Mean subjective 12 hour pain scale scores at rest and on movement showed large variability between patients. No signs or symptoms of ropivacaine toxicity were observed or reported on questioning. In this limited sample, extending the infusion period from the presently approved 48

  15. Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety

    PubMed Central

    Ley, David; Hansen-Pupp, Ingrid; Niklasson, Aimon; Domellöf, Magnus; Friberg, Lena E.; Borg, Jan; Löfqvist, Chatarina; Hellgren, Gunnel; Smith, Lois E.H.; Hård, Anna-Lena; Hellström, Ann

    2014-01-01

    BACKGROUND In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP. METHODS In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (GA) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900–1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47–168) h in dosages between 21 and 111 µg/kg/24 h. RESULTS Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75–100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded. CONCLUSION In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe. PMID:23095978

  16. Should β-lactam antibiotics be administered by continuous infusion in critically ill patients? A survey of Australia and New Zealand intensive care unit doctors and pharmacists.

    PubMed

    Cotta, Menino O; Dulhunty, Joel M; Roberts, Jason A; Myburgh, John; Lipman, Jeffrey

    2016-06-01

    Although there is a biological precedent for administration of β-lactam antibiotics by continuous or extended infusion, there is no definitive evidence of a survival benefit compared with intermittent administration. The aim of this study was to explore clinician uncertainty with regard to the administration of β-lactam antibiotics by continuous infusion. Doctors and pharmacists in Australian and New Zealand intensive care units (ICUs) were surveyed to investigate current β-lactam antibiotic administration practices as well as the degree of uncertainty regarding the benefit of continuous infusion of two commonly used broad-spectrum β-lactams, namely meropenem and piperacillin/tazobactam (TZP). There were 111 respondents to the survey. Intermittent infusion was reported as standard practice for meropenem (73.9%) and TZP (82.0%). A greater proportion of pharmacists compared with doctors believed continuous infusion to be more effective than intermittent administration (85.4% vs. 34.3%, respectively; P <0.001). Both groups reported uncertainty as to whether administration by continuous infusion resulted in better patient outcomes (65.9% and 74.6%, respectively; P = 0.85). Overall, 91.0% of respondents were prepared to enrol eligible patients into a definitive randomised controlled trial on β-lactam antibiotic administration. In conclusion, there is equipoise among clinicians working in Australian and New Zealand ICUs as to whether administration by continuous infusion offers a survival benefit in critically ill patients. PMID:27179814

  17. Impact of the Type of Continuous Insulin Administration on Metabolism in a Diabetic Rat Model.

    PubMed

    Schaschkow, A; Mura, C; Dal, S; Langlois, A; Seyfritz, E; Sookhareea, C; Bietiger, W; Peronet, C; Jeandidier, N; Pinget, M; Sigrist, S; Maillard, E

    2016-01-01

    Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC) injection in a basal and bolus scheme using insulin pens (injection) or pumps (preimplanted SC catheter). Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin) at the same dosage (4 IU/200 g/day) on rat metabolism and tissues. The rat weight and blood glucose levels were measured periodically after treatment. Immunostaining for signs of oxidative stress and for macrophages was performed on the liver and omental tissues. The continuous insulin delivery by pumps restored normoglycaemia, which induced the reduction of both reactive oxygen species and macrophage infiltration into the liver and omentum. Injections controlled the glucose levels for only a short period of time and therefore tissue stress and inflammation were elevated. In conclusion, the insulin administration mode has a crucial impact on rat metabolic parameters, which has to be taken into account when studies are designed. PMID:27504460

  18. Impact of the Type of Continuous Insulin Administration on Metabolism in a Diabetic Rat Model

    PubMed Central

    Schaschkow, A.; Dal, S.; Langlois, A.; Seyfritz, E.; Sookhareea, C.; Bietiger, W.; Peronet, C.; Jeandidier, N.; Pinget, M.; Sigrist, S.

    2016-01-01

    Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC) injection in a basal and bolus scheme using insulin pens (injection) or pumps (preimplanted SC catheter). Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin) at the same dosage (4 IU/200 g/day) on rat metabolism and tissues. The rat weight and blood glucose levels were measured periodically after treatment. Immunostaining for signs of oxidative stress and for macrophages was performed on the liver and omental tissues. The continuous insulin delivery by pumps restored normoglycaemia, which induced the reduction of both reactive oxygen species and macrophage infiltration into the liver and omentum. Injections controlled the glucose levels for only a short period of time and therefore tissue stress and inflammation were elevated. In conclusion, the insulin administration mode has a crucial impact on rat metabolic parameters, which has to be taken into account when studies are designed. PMID:27504460

  19. Continuous infusion of tracer norepinephrine may miscalculate unidirectional nerve uptake of norepinephrine in humans

    SciTech Connect

    Henriksen, J.H.; Christensen, N.J.; Ring-Larsen, H. )

    1989-08-01

    In order to evaluate uptake kinetics of norepinephrine (NE) in different tissues, a catheterization study was performed in control subjects (n = 6) and patients with enhanced sympathetic nervous activity (cirrhosis, n = 12) during constant intravenous infusion of L(3H)norepinephrine ((3H)NE) for 75 minutes. In spite of a higher NE spillover from kidneys in patients compared with controls (82 vs. 49 ng/min, p less than 0.01), renal extraction ratios of (3H)NE were similar in the two groups (0.33 vs. 0.32, NS), and no significant change was observed during the time of infusion. In contrast, liver-intestine extraction ratios of (3H)NE decreased significantly and equally with infusion time in patients (from 0.57 to 0.44, p less than 0.01) and controls (from 0.59 to 0.46, p less than 0.01). This was observed despite the fact that spillover of NE from this vascular bed was observed only in patients with cirrhosis and not in controls (41 vs. -5 ng/min, p less than 0.02). In the lower limb, net release of NE was similar in patients and controls, and extraction ratios of (3H)NE decreased almost equally with infusion time (from 0.35 to 0.30, p less than 0.01 and from 0.40 to 0.24, p less than 0.1, respectively). Whole-body clearance of (3H)NE decreased over time in patients (-6%, p less than 0.01) and controls (-20%, p less than 0.01), but significant difference was not observed between the groups. We conclude that failure to attain a steady state with respect to (3H)NE removal was demonstrated in areas of large tissue volume relative to blood flow.

  20. Perioperative Continuous Ropivacaine Wound Infusion in Laparoscopic Cholecystectomy: A Randomized Controlled Double-blind Trial.

    PubMed

    Fassoulaki, Argyro; Vassi, Emilia; Korkolis, Dimitrios; Zotou, Marianna

    2016-02-01

    Wound infusion with local anesthetics has been used for postoperative pain relief with variable results. This randomized, controlled, double-blind clinical trial examines the effect of ropivacaine infusion on pain after laparoscopic cholecystectomy. A total of 110 patients were randomly assigned to 2 groups. After induction of anesthesia a 75-mm catheter was inserted subcutaneously and connected to an elastomeric pump containing either 0.75% ropivacaine (ropivacaine group) or normal saline (control group) for 24 hours postoperatively. Before skin closure, each hole was infiltrated with 2 mL of 0.75% ropivacaine or normal saline according to randomization. Pain at rest, pain during cough, and analgesic consumption were recorded in the postanesthesia care unit and at 2, 4, 8, 24, and 48 hours postoperatively. Analgesic requirements and pain scores were recorded 1 and 3 months after surgery. The ropivacaine group reported less pain during cough (P=0.044) in the postanesthesia care unit (P=0.017) and 4 hours postoperatively (P=0.038). Ropivacaine wound infusion had no effect on late and chronic pain. PMID:26679680

  1. Lack of difference between continuous versus intermittent heparin infusion on maintenance of intra-arterial catheter in postoperative pediatric surgery: a randomized controlled study

    PubMed Central

    Witkowski, Maria Carolina; de Moraes, Maria Antonieta P.; Firpo, Cora Maria F.

    2013-01-01

    OBJECTIVE: To compare two systems of arterial catheters maintenance in postoperative pediatric surgery using intermittent or continuous infusion of heparin solution and to analyze adverse events related to the site of catheter insertion and the volume of infused heparin solution. METHODS: Randomized control trial with 140 patients selected for continuous infusion group (CIG) and intermittent infusion group (IIG). The variables analyzed were: type of heart disease, permanence time and size of the catheter, insertion site, technique used, volume of heparin solution and adverse events. The descriptive variables were analyzed by Student's t-test and the categorical variables, by chi-square test, being significant p<0.05. RESULTS: The median age was 11 (0-22) months, and 77 (55%) were females. No significant differences between studied variables were found, except for the volume used in CIG (12.0±1.2mL/24 hours) when compared to IIG (5.3±3.5mL/24 hours) with p<0.0003. CONCLUSIONS: The continuous infusion system and the intermittent infusion of heparin solution can be used for intra-arterial catheters maintenance in postoperative pediatric surgery, regardless of patient's clinical and demographic characteristics. Adverse events up to the third postoperative day occurred similarly in both groups. However, the intermittent infusion system usage in underweight children should be considered, due to the lower volume of infused heparin solution [ClinicalTrials.gov Identifier: NCT01097031]. PMID:24473958

  2. Infusion Methods for Continuous Interscalene Brachial Plexus Block for Postoperative Pain Control after Arthroscopic Rotator Cuff Repair

    PubMed Central

    Byeon, Gyeong Jo; Yoon, Ji Uk; Kim, Eun Jung; Baek, Seung Hoon; Ri, Hyun Su

    2015-01-01

    Background Infusion methods during regional analgesia using perineural catheters may influence the quality of postoperative analgesia. This study was conducted to compare the effects of combined or bolus-only infusion of 0.2% ropivacaine on the postoperative analgesia in interscalene brachial plexus block (ISBPB) with perineural catheterization. Methods Patients scheduled for arthroscopic rotator cuff repair were divided into two groups, one that would receive a combined infusion (group C, n = 32), and one that would receive intermittent infusion (group I, n = 32). A perineural catheter was inserted into the interscalene brachial plexus (ISBP) using ultrasound (US) and nerve stimulation, and 10 ml of 0.2% ropivacaine was administered. After the operation, group C received a continuous infusion of 4 ml/h, and a 4 ml bolus with a lockout interval of 60 min. Group I received only a 4 ml bolus, and the lockout interval was 30 min. Postoperative pain by the numeric rating scale (NRS) and the forearm muscle tone by the manual muscle test (MMT) were checked and evaluated at the following timepoints: preoperative, and postoperative 1, 4, 12, 24, 36, and 48 h. Supplemental opioid requirements, total consumed dose of local anesthetic, and adverse effects were compared between the two groups. Results Sixty-four patients completed the study and the postoperative values such as operation time, time to discharge, and operation site were comparable. There were no differences in NRS scores and supplemental opioid requirements between the two groups. The MMT scores of group I at 4 and 12 h after surgery were significantly higher than those of group C (P < 0.05). The total consumed dose of local anesthetic was significantly lower in group I than in group C (P < 0.05). The adverse effects were not different between the groups. Conclusions The bolus-only administration of 0.2% ropivacaine provided a similar analgesic effect with a lower total volume of local anesthetic and decreased

  3. Postoperative Pain Control with the Fentanyl Patch and Continuous Paravertebral Anesthetic Infusion after Posterior Occipitocervical Junction Surgery

    PubMed Central

    Sivakumar, Walavan; Karsy, Michael; Brock, Andrea

    2016-01-01

    Postoperative pain is a significant concern for patients who undergo surgery via a midline posterior approach to the occipitocervical junction and spinal axis. The development of the disposable, ambulatory pain pump presents a novel alternative for treatment of postoperative pain. The authors describe a multimodal treatment algorithm for postoperative pain after posterior occipitocervical junction surgery that uses the On-Q pain catheter system (I-Flow Corp., Lake Forest, CA) and a fentanyl patch. The On-Q PainBuster catheter system is a disposable, ambulatory device that allows for continuous anesthetic delivery directly into or adjacent to the wound. On-Q catheters are placed in the nuchal musculature for continuous infusion of 0.5% bupivacaine. The On-Q catheter infusion is continued for three days, and the catheters are then withdrawn. Patients are also provided with a transdermal fentanyl patch at the start of surgery. In regards to complications at our facility, there have been no cases of respiratory depression or arrest postoperatively and no wound infections, but one case of inadvertent subdural placement. The technique described for the use of the fentanyl patch and a continuous anesthetic delivery device in surgery of the occipitocervical junction presents a novel alternative to the current standard of care in pain control after suboccipital decompression. PMID:27433423

  4. Postoperative Pain Control with the Fentanyl Patch and Continuous Paravertebral Anesthetic Infusion after Posterior Occipitocervical Junction Surgery.

    PubMed

    Sivakumar, Walavan; Karsy, Michael; Brock, Andrea; Schmidt, Richard H

    2016-01-01

    Postoperative pain is a significant concern for patients who undergo surgery via a midline posterior approach to the occipitocervical junction and spinal axis. The development of the disposable, ambulatory pain pump presents a novel alternative for treatment of postoperative pain. The authors describe a multimodal treatment algorithm for postoperative pain after posterior occipitocervical junction surgery that uses the On-Q pain catheter system (I-Flow Corp., Lake Forest, CA) and a fentanyl patch. The On-Q PainBuster catheter system is a disposable, ambulatory device that allows for continuous anesthetic delivery directly into or adjacent to the wound. On-Q catheters are placed in the nuchal musculature for continuous infusion of 0.5% bupivacaine. The On-Q catheter infusion is continued for three days, and the catheters are then withdrawn. Patients are also provided with a transdermal fentanyl patch at the start of surgery. In regards to complications at our facility, there have been no cases of respiratory depression or arrest postoperatively and no wound infections, but one case of inadvertent subdural placement. The technique described for the use of the fentanyl patch and a continuous anesthetic delivery device in surgery of the occipitocervical junction presents a novel alternative to the current standard of care in pain control after suboccipital decompression. PMID:27433423

  5. In Vivo MR Imaging of Pulmonary Perfusion and Gas Exchange in Rats via Continuous Extracorporeal Infusion of Hyperpolarized 129Xe

    PubMed Central

    Cleveland, Zackary I.; Möller, Harald E.; Hedlund, Laurence W.; Nouls, John C.; Freeman, Matthew S.; Qi, Yi; Driehuys, Bastiaan

    2012-01-01

    Background Hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10%) and large chemical shift range (>200 ppm) in tissues allow HP 129Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP 129Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP 129Xe as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP 129Xe signal. Methods and Principal Findings Here, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse 129Xe into the arterial blood of live rats with an extracorporeal (EC) circuit. The resulting gas-phase 129Xe signal is sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2×2×2 mm3. We also show that the 129Xe signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation. Conclusions Extracorporeal infusion of HP 129Xe enables rapid, 3D MR imaging of rat lungs and, when combined with ventilation imaging, will permit spatially resolved studies of the ventilation-perfusion ratio in small animals. Moreover, EC infusion should allow 129Xe to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP 129Xe. PMID:22363613

  6. 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 ...

  7. Tocolysis for recurrent preterm labor using a continuous subcutaneous infusion pump.

    PubMed

    Allbert, J R; Johnson, C; Roberts, W E; Martin, R W; Gookin, K S; Morrison, J C

    1994-08-01

    This study attempted to determine the best method of treatment for patients with recurrent preterm labor: administration of terbutaline via an automated, programmable, subcutaneous infusion pump or oral terbutaline. In this retrospective, controlled study, 32 patients diagnosed with recurrent preterm labor, as determined by persistent uterine contractions with cervical change, were treated with a programmable infusion pump adjusted to control uterine contraction frequency to < or = 4 contractions per hour. Patients in this group were matched for age, race, parity, gestational age and cervical dilation at diagnosis of recurrent preterm labor in subjects taking oral terbutaline. The patients receiving oral terbutaline were given an average of 6.5 mg every four to six hours to maintain uterine quiescence, while those in the pump group were given basal rates of terbutaline and in addition received four to six boluses per day (< 3 mg/d total dose) to achieve this outcome. Patients using the pump were more likely to reach term and less likely to fail tocolytic therapy than were those taking oral terbutaline. The terbutaline pump appeared to be more successful in prolonging pregnancies to term after the diagnosis of recurrent preterm labor than did oral terbutaline. PMID:7996525

  8. A comparison of continuous subcutaneous paliperidone infusion and repeated subcutaneous injection of risperidone free-base in rats.

    PubMed

    Marchese, G; Pittau, B; Casu, G; Peddio, G; Spada, G P; Pira, M; Deriu, A; Portesani, F; Pisu, C; Lazzari, P; Pani, L

    2010-03-01

    It is proposed that to achieve a therapeutic effect in schizophrenia patients, dopamine D(2)-receptor occupancy by antipsychotics within the striatum must exceed 60-65%. However, at high levels of D(2)-receptor occupancy, the risk of extrapyramidal symptoms (EPS) is increased. Following oral dosing of antipsychotics, peaks and troughs in plasma drug concentrations may be mirrored by fluctuations in D(2)-receptor occupancy. Paliperidone, a novel antipsychotic available as extended-release tablets (paliperidone ER), is the major active metabolite of risperidone and exhibits a plasma pharmacokinetic profile with reduced peak-trough fluctuations and consistent D(2)-receptor occupancy compared with conventional oral antipsychotic formulations. Using formulations that resemble those in clinical practice, this study provides a preclinical evaluation of the pharmacological properties of paliperidone ER and risperidone immediate-release formulation in terms of consistent antipsychotic efficacy over time and extrapyramidal symptom liability. Significant fluctuations in inhibition of d-amphetamine-induced hyperlocomotion were observed for repeated subcutaneous (SC) risperidone injections, whereas stable inhibitory efficacy was demonstrated during continuous SC paliperidone infusion. Similarly, significant fluctuations in latency on-bar were observed with repeated SC risperidone injections, whereas significantly lower latency on-bar was demonstrated following continuous SC paliperidone infusion. These results in an animal model suggest that although risperidone and paliperidone demonstrate similar pharmacologic effects, continuous administration of paliperidone achieves more stable antipsychotic efficacy with reduced motor impairment, akin to the effects observed with paliperidone ER in clinical studies. PMID:19640686

  9. The impact of glucose-insulin-potassium infusion in acute myocardial infarction on infarct size and left ventricular ejection fraction [ISRCTN56720616

    PubMed Central

    van der Horst, Iwan CC; Ottervanger, Jan Paul; van 't Hof, Arnoud WJ; Reiffers, Stoffer; Miedema, Kor; Hoorntje, Jan CA; Dambrink, Jan-Henk E; Gosselink, AT Marcel; Nijsten, Maarten WN; Suryapranata, Harry; de Boer, Menko-Jan; Zijlstra, Felix

    2005-01-01

    Background Favorable clinical outcomes have been observed with glucose-insulin-potassium infusion (GIK) in acute myocardial infarction (MI). The mechanisms of this beneficial effect have not been delineated clearly. GIK has metabolic, anti-inflammatory and profibrinolytic effects and it may preserve the ischemic myocardium. We sought to assess the effect of GIK infusion on infarct size and left ventricular function, as part of a randomized controlled trial. Methods Patients (n = 940) treated for acute MI by primary percutaneous coronary intervention (PCI) were randomized to GIK infusion or no infusion. Endpoints were the creatinine kinase MB-fraction (CK-MB) and left ventricular ejection fraction (LVEF). CK-MB levels were determined 0, 2, 4, 6, 24, 48, 72 and 96 hours after admission and the LVEF was measured before discharge. Results There were no differences between the two groups in the time course or magnitude of CK-MB release: the peak CK-MB level was 249 ± 228 U/L in the GIK group and 240 ± 200 U/L in the control group (NS). The mean LVEF was 43.7 ± 11.0 % in the GIK group and 42.4 ± 11.7% in the control group (P = 0.12). A LVEF ≤ 30% was observed in 18% in the controls and in 12% of the GIK group (P = 0.01). Conclusion Treatment with GIK has no effect on myocardial function as determined by LVEF and by the pattern or magnitude of enzyme release. However, left ventricular function was preserved in GIK treated patients. PMID:15932638

  10. Decreased insulin sensitivity due to continuous nutrient administration in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic TPN compared to intermittent formula feeding has been shown to induce hepatic insulin resistance and steatosis in neonatal pigs. We hypothesized that the route of feeding (IV vs. enteral) rather than the nature of the diet (elemental vs polymeric) or the feeding regimen (continuous vs interm...

  11. Induction of ovulation in the acyclic postpartum ewe following continuous, low-dose subcutaneous infusion of GnRH.

    PubMed

    Fray, M D; Lamming, G E; Haresign, W

    1995-04-15

    demonstrate that although a low dose, continuous infusion of GnRH can increase tonic LH concentrations sufficient to promote a preovulatory LH surge and induce ovulation, behavioral estrus and normal luteal function do not consistently follow ovulation in the progestagen-primed, postpartum ewe. PMID:16727689

  12. The single-biopsy approach in determining protein synthesis in human slow-turning-over tissue: use of flood-primed, continuous infusion of amino acid tracers.

    PubMed

    Holm, Lars; Reitelseder, Søren; Dideriksen, Kasper; Nielsen, Rie H; Bülow, Jacob; Kjaer, Michael

    2014-06-01

    Muscle protein synthesis (MPS) rate is determined conventionally by obtaining two or more tissue biopsies during a primed, continuous infusion of a stable isotopically labeled amino acid. The purpose of the present study was to test whether tracer priming given as a flooding dose, thereby securing an instantaneous labeling of the tissue pools of free tracee amino acids, followed by a continuous infusion of the same tracer to maintain tracer isotopic steady state, could be used to determine the MPS rate over a prolonged period of time by obtaining only a single tissue biopsy. We showed that the tracer from the flood prime appeared immediately in the muscle free pool of amino acids and that this abundance could be kept constant by a subsequent continuous infusion of the tracer. When using phenylalanine as tracer, the flood-primed, continuous infusion protocol does not stimulate the MPS rate per se. In conclusion, the flood-primed, continuous infusion protocol using phenylalanine as tracer can validly be used to measure the protein synthesis rate in human in vivo experiments by obtaining only a single tissue biopsy after a prolonged infusion period. PMID:24760987

  13. Stimulation of epithelial cell proliferation of isolated distal colon of rats by continuous colonic infusion of ammonia or short-chain fatty acids is nonadditive.

    PubMed

    Ichikawa, H; Sakata, T

    1998-05-01

    Dietary fibers accelerate colonic epithelial cell proliferation at least in part by modulating bacterial metabolism in the large intestine. Ammonia and short-chain fatty acids (SCFA) are major metabolites of hindgut bacteria and are believed to affect epithelial cell kinetics of the colon. However, the effect of luminal ammonia itself and the possible interaction of ammonia with SCFA on colonic epithelial cell proliferation have not yet been studied. The colon of rats was surgically isolated and continuously administered infusates with saline, ammonia, SCFA or both into the isolated colon for 7 d in a two-way factorial design. On d 7, vincrystine sulfate was administered intravenously to cause metaphase arrest. The activity of epithelial cell proliferation in the distal colon was estimated by using a stathmokinetic method and by histologic examination. The crypt size was significantly larger in rats given infusates containing SCFA than in rats given infusates without SCFA. Infusion of ammonia or SCFA significantly stimulated colonic epithelial cell proliferation compared with the saline infusion. Infusion of both ammonia and SCFA resulted in accumulated mitoses per crypt that did not differ from the other three infusions although the value tended to be lower than when SCFA alone were infused. Thus, stimulation of epithelial cell proliferation by ammonia and SCFA is not additive, and the interaction between them should be considered when the effects of dietary fibers on gut epithelial proliferation are investigated. PMID:9566991

  14. Phase I/II Trial of Dose-Escalated Busulfan Delivered by Prolonged Continuous Infusion in Allogeneic Transplant Patients.

    PubMed

    Shea, Thomas C; Walko, Christine; Chung, Yunro; Ivanova, Anastasia; Sheets, Julia; Rao, Kamakshi; Gabriel, Don; Comeau, Terry; Wood, William; Coghill, James; Armistead, Paul; Sarantopoulos, Stefanie; Serody, Jonathan

    2015-12-01

    Intensive chemotherapy or chemotherapy plus irradiation and allogeneic stem cell transplantation can be curative for patients with hematologic diseases. Reduced-intensity transplants can also achieve cure and result in less treatment-related mortality but higher relapse rates. Thus, optimizing the conditioning regimens used in allogeneic transplantation remains an important goal. We conducted a phase I/II trial to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a continuous infusion of busulfan over 90 hours in conjunction with fludarabine followed by allogeneic related or unrelated donor transplant. Fifty-four patients with advanced hematologic malignancies were enrolled on this study. The MTD was identified as a 24-hour area under the curve (AUC) of approximately 7095 μM/min, which represents a 43% increase over the standard total daily AUC dose of 4800 μM/min given by intermittent schedules. DLTs at doses over 8000 μM/min were identified by a desquamative skin rash and mucositis. No dose-related increase in hepatic, pulmonary, or other organ toxicities were seen, whereas efficacy appeared to be improved at higher dose levels. Continuous-infusion busulfan with intermittent fludarabine provides an alternative treatment strategy that is generally well tolerated and permits an increase in total busulfan dose with encouraging efficacy. (NCI study no. NCT00448357.). PMID:26210442

  15. Continuous versus Short-Term Infusion of Cefuroxime: Assessment of Concept Based on Plasma, Subcutaneous Tissue, and Bone Pharmacokinetics in an Animal Model

    PubMed Central

    Bibby, Bo M.; Hardlei, Tore F.; Bue, Mats; Kerrn-Jespersen, Sigrid; Fuursted, Kurt; Søballe, Kjeld; Birke-Sørensen, Hanne

    2014-01-01

    The relatively short half-lives of most β-lactams suggest that continuous infusion of these time-dependent antimicrobials may be favorable compared to short-term infusion. Nevertheless, only limited solid-tissue pharmacokinetic data are available to support this theory. In this study, we randomly assigned 12 pigs to receive cefuroxime as either a short-term or continuous infusion. Measurements of cefuroxime were obtained every 30 min in plasma, subcutaneous tissue, and bone. For the measurements in solid tissues, microdialysis was applied. A two-compartment population model was fitted separately to the drug concentration data for the different tissues using a nonlinear mixed-effects regression model. Estimates of the pharmacokinetic parameters and time with concentrations above the MIC were derived using Monte Carlo simulations. Except for subcutaneous tissue in the short-term infusion group, the tissue penetration was incomplete for all tissues. For short-term infusion, the tissue penetration ratios were 0.97 (95% confidence interval [CI], 0.67 to 1.39), 0.61 (95% CI, 0.51 to 0.73), and 0.45 (95% CI, 0.36 to 0.56) for subcutaneous tissue, cancellous bone, and cortical bone, respectively. For continuous infusion, they were 0.53 (95% CI, 0.33 to 0.84), 0.38 (95% CI, 0.23 to 0.57), and 0.27 (95% CI, 0.13 to 0.48) for the same tissues, respectively. The absolute areas under the concentration-time curve were also lower in the continuous infusion group. Nevertheless, a significantly longer time with concentrations above the MIC was found for continuous infusion up until MICs of 4, 2, 2, and 0.5 μg/ml for plasma and the same three tissues mentioned above, respectively. For drugs with a short half-life, like cefuroxime, continuous infusion seems to be favorable compared to short-term infusion; however, incomplete tissue penetration and high MIC strains may jeopardize the continuous infusion approach. PMID:25313214

  16. Toward Closing the Loop: An Update on Insulin Pumps and Continuous Glucose Monitoring Systems

    PubMed Central

    Aye, Tandy; Block, Jen; Buckingham, Bruce

    2010-01-01

    Synoposis In this paper we review current pump and continuous glucose monitoring therapy and what will be required to integrate these systems into closed-loop control. Issues with sensor accuracy, lag time and calibration are discussed as well as issues with insulin pharmacodynamics which result in a delayed onset of insulin action in a closed-loop system. A stepwise approach to closed-loop therapy is anticipated where the first systems will suspend insulin delivery based on actual or predicted hypoglycemia. Subsequent systems may “control-to-range” limiting the time spent in hyperglycemia by mitigating the effects of a missed food bolus or underestimate of consumed carbohydrates while minimizing the risk of hypoglycemia. PMID:20723823

  17. Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy.

    PubMed

    Das, Samaresh; Al-Mashani, Ali; Suri, Neelam; Salhotra, Neeraj; Chatterjee, Nilay

    2016-08-01

    An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofolfentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors' knowledge, this is the first awake craniotomy conducted successfully in Oman. PMID:27606116

  18. Combination of Continuous Dexmedetomidine Infusion with Titrated Ultra-Low-Dose Propofol-Fentanyl for an Awake Craniotomy

    PubMed Central

    Das, Samaresh; Al-Mashani, Ali; Suri, Neelam; Salhotra, Neeraj; Chatterjee, Nilay

    2016-01-01

    An awake craniotomy is a continuously evolving technique used for the resection of brain tumours from the eloquent cortex. We report a 29-year-old male patient who presented to the Khoula Hospital, Muscat, Oman, in 2016 with a two month history of headaches and convulsions due to a space-occupying brain lesion in close proximity with the left motor cortex. An awake craniotomy was conducted using a scalp block, continuous dexmedetomidine infusion and a titrated ultra-low-dose of propofolfentanyl. The patient remained comfortable throughout the procedure and the intraoperative neuropsychological tests, brain mapping and tumour resection were successful. This case report suggests that dexmedetomidine in combination with titrated ultra-low-dose propofolfentanyl are effective options during an awake craniotomy, ensuring optimum sedation, minimal disinhibition and a rapid recovery. To the best of the authors’ knowledge, this is the first awake craniotomy conducted successfully in Oman. PMID:27606116

  19. Adipose Tissue Promotes a Serum Cytokine Profile Related to Lower Insulin Sensitivity after Chronic Central Leptin Infusion

    PubMed Central

    Burgos-Ramos, Emma; Canelles, Sandra; Perianes-Cachero, Arancha; Arilla-Ferreiro, Eduardo; Argente, Jesús; Barrios, Vicente

    2012-01-01

    Obesity is an inflammatory state characterized by an augment in circulating inflammatory factors. Leptin may modulate the synthesis of these factors by white adipose tissue decreasing insulin sensitivity. We have examined the effect of chronic central administration of leptin on circulating levels of cytokines and the possible relationship with cytokine expression and protein content as well as with leptin and insulin signaling in subcutaneous and visceral adipose tissues. In addition, we analyzed the possible correlation between circulating levels of cytokines and peripheral insulin resistance. We studied 18 male Wistar rats divided into controls (C), those treated icv for 14 days with a daily dose of 12 μg of leptin (L) and a pair-fed group (PF) that received the same food amount consumed by the leptin group. Serum leptin and insulin were measured by ELISA, mRNA levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and tumor necrosis factor-α (TNF-α) by real time PCR and serum and adipose tissue levels of these cytokines by multiplexed bead immunoassay. Serum leptin, IL-2, IL-4, IFN-γ and HOMA-IR were increased in L and TNF-α was decreased in PF and L. Serum leptin and IL-2 levels correlate positively with HOMA-IR index and negatively with serum glucose levels during an ip insulin tolerance test. In L, an increase in mRNA levels of IL-2 was found in both adipose depots and IFN-γ only in visceral tissue. Activation of leptin signaling was increased and insulin signaling decreased in subcutaneous fat of L. In conclusion, leptin mediates the production of inflammatory cytokines by adipose tissue independent of its effects on food intake, decreasing insulin sensitivity. PMID:23056516

  20. Continuous infusion of angiotensin II modulates hypertrophic differentiation and apoptosis of chondrocytes in cartilage formation in a fracture model mouse.

    PubMed

    Kawahata, Hirohisa; Sotobayashi, Daisuke; Aoki, Motokuni; Shimizu, Hideo; Nakagami, Hironori; Ogihara, Toshio; Morishita, Ryuichi

    2015-06-01

    Although components of the renin-angiotensin system (RAS) are reported to be expressed in cultured chondrocytes and cartilage, little is known about the precise function of Angiotensin II (Ang II) in chondrocytes. In this study, we employed a rib fracture model mouse to investigate the effect of Ang II on chondrocytes. Ang II type 1 receptor (AT1R) was expressed in chondrocytes in the growth plate of mouse tibia. Continuous infusion of Ang II to rib-fractured mice resulted in a significant increase in the volume of cartilage, suggesting Ang II-induced hypertrophic differentiation of chondrocytes. It was also confirmed by a significant increase in the mRNA expression of Sox9 and runt-related transcription factor 2 (Runx2), which are genes related to chondrocyte differentiation, and type X collagen, matrix metalloproteinase (MMP)-13 and Indian hedgehog (Ihh), which are hypertrophic chondrocyte-specific molecular markers. Chondrocyte hypertrophy with upregulation of these genes was attenuated by administration of olmesartan, an AT1R blocker, but not by hydralazine. Moreover, Ang II infusion significantly suppressed apoptosis of chondrocytes, accompanied by significant induction of mRNA expression of bcl-2 and bcl-xL. Olmesartan, but not hydralazine, significantly attenuated the reduction of apoptotic cells and the increase in anti-apoptotic genes induced by Ang II infusion. Overall, the present study demonstrated that Ang II promoted hypertrophic differentiation of chondrocytes and reduced apoptosis of hypertrophic chondrocytes independently of high blood pressure. The present data indicate the role of Ang II in cartilage, and might provide a new concept for treatment of cartilage diseases. PMID:25693858

  1. Feeding, body weight, and sensitivity to non-ingestive reward stimuli during and after 12-day continuous central infusions of melanocortin receptor ligands.

    PubMed

    Cabeza de Vaca, S; Hao, J; Afroz, T; Krahne, L L; Carr, K D

    2005-11-01

    The brain melanocortin system mediates downstream effects of hypothalamic leptin and insulin signaling. Yet, there have been few studies of chronic intracerebroventricular (i.c.v.) melanocortin receptor (MCR) agonist or antagonist infusion. Although there is evidence of interaction between melanocortin and dopamine (DA) systems, effects of chronic MCR ligand infusion on behavioral sensitivity to non-ingestive reward stimuli have not been investigated. The objective of this study was to investigate effects of chronic i.c.v. infusion of the MCR agonist, MTII, and the MCR antagonist, SHU9119, on food intake, body weight, and sensitivity to rewarding lateral hypothalamic electrical stimulation (LHSS) and the reward-potentiating (i.e., threshold-lowering) effect of D-amphetamine. The MCR antagonist, SHU9119 (0.02 microg/h) produced sustained hyperphagia and weight gain during the 12-day infusion period, followed by compensatory hypophagia and an arrest of body weight gain during the 24-day post-infusion period. At no point during the experiment was sensitivity to LHSS or D-amphetamine (0.25mg/kg, i.p.) altered. The MCR agonist, MTII (0.02 microg/h) produced a brief hypophagia (3 days) followed by a return to control levels of daily intake, but with body weight remaining at a reduced level throughout the 12-day infusion period. This was followed by compensatory hyperphagia and weight gain during the 24-day post-infusion period. There was no change in sensitivity to non-ingestive reward stimuli during the infusion of MTII. However, sensitivity to D-amphetamine was increased during the 24-day post-infusion period. It therefore seems that changes in ingestive behavior that occur during chronic MCR ligand infusion may not affect the response to non-ingestive reward stimuli. However, it is possible that the drive to re-feed and restore body weight following MCR agonist treatment includes neuroadaptations that enhance the incentive effects of drug stimuli. PMID:15894406

  2. Pharmacokinetics of ceftazidime in serum and suction blister fluid during continuous and intermittent infusions in healthy volunteers.

    PubMed Central

    Mouton, J W; Horrevorts, A M; Mulder, P G; Prens, E P; Michel, M F

    1990-01-01

    The pharmacokinetics of ceftazidime were investigated during intermittent (II) and continuous (CI) infusion in eight healthy male volunteers in a crossover fashion. The total daily dose was 75 mg/kg of body weight per 24 h in both regimens, given in three doses of 25 mg/kg/8 h (II) or 60 mg/kg/24 h with 15 mg/kg as a loading dose (CI). After the third dose (II) and during CI, serum and blister fluid samples were taken. Seven new blisters were raised for each timed sample by a suction blister technique. Blisters took 90 min to form. Samples were then taken from four blisters (A samples) and 1 h later were taken from the remaining three (B samples). The concentration of ceftazidime was determined using a high-performance liquid chromatography method. After II, the concentrations in serum immediately after infusion (t = 30 min) and 8 h after the start of the infusion were 137.9 (standard deviation [SD], 27.5) and 4.0 (SD, 0.7) micrograms/ml, respectively. The half-life at alpha phase (t1/2 alpha) was 9.6 min (SD, 4.6), t1/2 beta was 94.8 min (SD, 5.4), area under the concentration-time curve (AUC) was 285.4 micrograms.h/ml (SD, 22.7), total body clearance was 0.115 liter/h.kg (SD, 0.022), and volume of distribution at steady state was 0.178 liter/kg (SD, 0.023). The blister fluid (A) samples showed a decline in concentration parallel to that of the concentrations in serum during the elimination phase with a ratio of 1:1. The t1/2 of the A samples was 96.4 min (SD, 3.2). The concentration of ceftazidime in the B blister fluid samples was significantly higher (27%) than in the A samples over time. This shows that blisters may behave as a separate compartment and establishes the need to raise new blisters for each timed sample. The mean AUC/h during continuous infusion was 21.3 micrograms . h/ml (SD, 3.0). The total body clearance was 0.113 liter/h . kg (SD, 0.018), the urinary clearance was 0.105 liter/h . kg (SD, 0.012), and the ceftazidime/creatinine clearance ratio

  3. Tripartite neuroendocrine activation of the human growth hormone (GH) axis in women by continuous 24-hour GH-releasing peptide infusion: pulsatile, entropic, and nyctohemeral mechanisms.

    PubMed

    Shah, N; Evans, W S; Bowers, C Y; Veldhuis, J D

    1999-06-01

    Despite the discovery of potent GH-releasing peptides (GHRPs) more than 15 yr ago and the recent cloning of human, rat, and pig GHRP receptors in the hypothalamus and pituitary gland, the neuroregulatory mechanisms of action of GHRP agonists on the human hypothalamo-somatotroph unit are not well delineated. To gain such clinical insights, we evaluated the ultradian (pulsatile), entropic (pattern orderliness), and nyctohemeral GH secretory responses during continuous 24-h i.v. infusion of saline vs. the most potent clinically available hexapeptide, GHRP-2 (1 microg/kg x h) in estrogen-unreplaced (mean serum estradiol, 12 +/- 2.4 pg/mL) postmenopausal women (n = 7) in a paired, randomized design. Blood was sampled every 10 min for 24 h during infusions and was assayed by ultrasensitive GH chemiluminescence assay. Pulsatile GH secretion was quantitated by deconvolution analysis, orderliness of GH release patterns by the approximate entropy statistic, and 24-h GH rhythmicity by cosinor analysis. Statistical analysis revealed that GHRP-2 elicited a 7.7-fold increase in (24-h) mean serum (+/-SEM) GH concentrations, viz. from 0.32 +/- 0.042 (saline) to 2.4 +/- 0.34 microg/L (GHRP-2; P = 0.0006). This occurred via markedly stimulated pulsatile GH release, namely a 7.1-fold augmentation of GH secretory burst mass: 0.87 +/- 0.18 (control) vs. 6.3 +/- 1.3 microg/L (GHRP-2; P = 0.0038). Enhanced GH pulse mass reflected a commensurate 10-fold (P = 0.023) rise in GH secretory burst amplitude [maximal GH secretory rate (micrograms per L/min) attained within a secretory pulse] with no prolongation in event duration. GH burst frequency, interpulse interval, and calculated GH half-life were all invariant of GHRP-2 treatment. Concurrently, as detected in the ultrasensitive GH assay, GHRP-2 augmented deconvolution-estimated interpulse (basal) GH secretion by 4.5-fold (P = 0.025). The approximate entropy of 24-h serum GH concentration profiles rose significantly during GHRP-2 infusion

  4. Determinants of Calcium Infusion Rate During Continuous Veno-venous Hemofiltration with Regional Citrate Anticoagulation in Critically Ill Patients with Acute Kidney Injury

    PubMed Central

    Liu, De-Lin; Huang, Li-Feng; Ma, Wen-Liang; Ding, Qi; Han, Yue; Zheng, Yue; Li, Wen-Xiong

    2016-01-01

    Background: It is unclear that how to decide the calcium infusion rate during continuous veno-venous hemofiltration (CVVH) with regional citrate anticoagulation (RCA). This study aimed to assess the determinants of calcium infusion rate during CVVH with RCA in critically ill patients with acute kidney injury (AKI). Methods: A total of 18 patients with AKI requiring CVVH were prospectively analyzed. Postdilution CVVH was performed with a fixed blood flow rate of 150 ml/min and a replacement fluid flow rate of 2000 ml/h for each new circuit. The infusion of 4% trisodium citrate was started at a rate of 29.9 mmol/h prefilter and adjusted according to postfilter ionized calcium. The infusion of 10% calcium gluconate was initiated at a rate of 5.5 mmol/h and adjusted according to systemic ionized calcium. The infusion rate of trisodium citrate and calcium gluconate as well as ultrafiltrate flow rate were recorded at 1, 2, 4, 6, 12, and 24 h after starting CVVH, respectively. The calcium loss rate by CVVH was also calculated. Results: Fifty-seven sessions of CVVH were performed in 18 AKI patients. The citrate infusion rate, calcium loss rate by CVVH, and calcium infusion rate were 31.30 (interquartile range: 2.70), 4.60 ± 0.48, and 5.50 ± 0.35 mmol/h, respectively. The calcium infusion rate was significantly higher than that of calcium loss rate by CVVH (P < 0.01). The correlation coefficient between the calcium and citrate infusion rates, and calcium infusion and calcium loss rates by CVVH was −0.031 (P > 0.05) and 0.932 (P < 0.01), respectively. In addition, calcium infusion rate (mmol/h) = 1.77 + 0.8 × (calcium loss rate by CVVH, mmol/h). Conclusions: The calcium infusion rate correlates significantly with the calcium loss rate by CVVH but not with the citrate infusion rate in a fixed blood flow rate during CVVH with RCA. PMID:27411455

  5. A comparison of the effects of continuous ketamine infusion and halothane on oxygenation during one-lung anaesthesia in dogs.

    PubMed

    Lumb, P D; Silvay, G; Weinreich, A I; Shiang, H

    1979-09-01

    It has been shown that a continuous infusion of ketamine during one-lung anaesthesia combined with a 50 per cent oxygen-curare anaesthetic technique will provide consistently lower shunt fraction and higher Pao2 compared with halothane under the same experimental conditions. Because no additional factor was observed which could account for these changes and because the responses of the animals to the two anaesthetic agents were similar--the only difference being a different initial set point--the experimental model may be considered adequate. In the authors' view the difference in shunt fractions may be attributed to a more stable hypoxic reflex during ketamine anaesthesia. Further experimentation will be necessary to fully exclude the possibility of sequence-related changes affecting some of these results and to determine whether or not certain groups of dogs respond in a qualitatively different fashion. PMID:487234

  6. Clinical management of patients with advanced Parkinson's disease treated with continuous intestinal infusion of levodopa/carbidopa.

    PubMed

    Santos García, Diego; Martínez Castrillo, Juan Carlos; Puente Périz, Víctor; Seoane Urgorri, Agustín; Fernández Díez, Servando; Benita León, Vicente; Udaeta Baldivieso, Beatriz; Campolongo Perillo, Antonia; Mariscal Pérez, Natividad

    2016-06-01

    Patients with Parkinson's disease often have a good initial response to dopaminergic therapy but later usually develop motor fluctuations and dyskinesia. In these patients, continuous infusion of levodopa-carbidopa intestinal gel (LCIG) allows for maintaining adequate dopamine levels and for improving motor and nonmotor symptoms, as well as quality of life and autonomy. Adequate candidate selection and follow-up are crucial for treatment success. Management should be multidisciplinary, and patient and caregiver education is a priority. This expert consensus document has been developed by a team of neurologists, gastroenterologists and nurses who have a vast experience in LCIG therapy, with an intention to provide knowledge and tools to facilitate patient management throughout all phases of LCIG treatment process. PMID:27075968

  7. Effects of Continuous Intravenous Infusion of Methoxamine on the Intraoperative Hemodynamics of Elderly Patients Undergoing Total Hip Arthroplasty

    PubMed Central

    Sun, Defeng; Wu, Yue; Yang, Lin; Han, Jun; Liu, Ruochuan; Wang, Lijie

    2014-01-01

    Background Hemodynamic disturbances are common during continuous epidural anesthesia in elderly patients undergoing total hip arthroplasty. This study aimed to investigate the effects of methoxamine on the intraoperative hemodynamics in elderly patients undergoing total hip arthroplasty under epidural anesthesia. Material/Methods This prospective study included 150 elderly patients undergoing elective total hip arthroplasty under epidural anesthesia. Patients were randomly assigned into 5 groups (n=30 per group): a control group receiving saline (Group C), a dopamine group receiving 7 μg/kg/min dopamine (Group D), and methoxamine groups receiving 1, 2, or 3 μg/kg/min methoxamine (Groups M1, M2, and M3, respectively). Hemodynamic parameters were assessed 10 min before anesthesia (T1); 10 min (T2), 20 min, (T3), 30 min (T4), and 60 min (T5) after anesthesia; and at the conclusion of surgery (T6). Results At T2–T6, the mean arterial pressure, central venous pressure, cardiac output, stroke volume, stroke volume ratio, and pulmonary vascular resistance were higher in Groups D, M2, and M3 compared to Group C (p<0.05). Compared to Group D, the heart rate and rate pressure product were significantly lower in Groups M1–M3. Infusion volume, ephedrine dose, and postoperative 24-h urine volume were significantly lower and intraoperative urine volume was significantly greater in Groups D, M2, and M3 compared with Group C. Hypertension occurred more frequently in Group M3 than in any other group. Conclusions Continuous intravenous infusion of 2 μg/kg/min methoxamine is safe and effective in maintaining hemodynamic stability in elderly patients undergoing total hip arthroplasty. PMID:25326008

  8. Insulin Test

    MedlinePlus

    ... people with type 2 diabetes , polycystic ovarian syndrome (PCOS) , prediabetes or heart disease , or metabolic syndrome . A ... resistance), especially in obese individuals and those with PCOS . This test involves an IV-infusion of insulin, ...

  9. A phase I trial of docetaxel and 5-day continuous infusion of 5-fluorouracil in patients with advanced or recurrent breast cancer.

    PubMed Central

    Ando, M.; Watanabe, T.; Sasaki, Y.; Ying, D. F.; Omuro, Y.; Katsumata, N.; Narabayashi, M.; Tokue, Y.; Fujii, H.; Igarashi, T.; Wakita, H.; Ohtsu, T.; Itoh, K.; Adachi, I.; Taguchi, T.

    1998-01-01

    To determine the maximum-tolerated doses (MTDs), the dose-limiting toxicities (DLTs) and the recommended doses for further trials of docetaxel in combination with a 5-day continuous infusion of 5-fluorouracil (5-FU) in advanced or recurrent breast cancer patients who had been treated previously with at least one chemotherapeutic regimen, patients were treated with docetaxel as a 1-h infusion on day 1 followed by 5-FU as a continuous infusion on days 1 through 5 every 3-4 weeks. Three or six patients were assessed at the following escalating dose levels of docetaxel/5-FU per day: 40/150, 40/300, 50/300, 50/500 and 60/500 mg m(-2). Nineteen patients entered this trial, of whom 18 could be assessed for adverse event and therapeutic efficacy. The DLTs were neutropenia and diarrhoea. The MTDs were 60 mg m(-2) of docetaxel on day 1 and 500 mg m(-2) per day of 5-day continuous infusion of 5-FU. One of 18 patients achieved a complete response and eight achieved partial response (over all response rate: 50%). The recommended doses of docetaxel and 5-day continuous infusion of 5-FU for a phase II trial are 50 mg m(-2) and 500 mg m(-2) per day every 3 or 4 weeks. PMID:9667671

  10. A Micro-PIV Study of the Pulsed Micro-Flows Driven by an Insulin Pump

    NASA Astrophysics Data System (ADS)

    Wang, Bing; Demuren, Ayodeji; Gyuricsko, Eric; Hu, Hui

    2009-11-01

    In recent years, there is a surge in the popularity of using insulin pump or continuous subcutaneous insulin infusion therapy, as opposed to multiple daily injections by insulin syringe or an insulin pen. Some case studies have suggested that insulin delivery failure may be caused by precipitation of insulin within the infusion set. Speculation also exists that the flow of insulin through an insulin infusion set may be reduced or inhibited by air bubbles entrained into the micro-sized tubing system since there are chances that air be introduced into the insulin reservoir during the filling process. In the present study, a microscopic Particle Image Velocimtry (micro-PIV) system was used to characterize the transient behavior of the pulsed micro-flows inside the micro-sized tubing system of an insulin infusion set with insulin pump operating in basal mode (i.e., pulsed insulin pumping). The effects of the air bubbles entrained into the micro-sized tubing system on the insulin delivery process were assessed based on the micro-PIV measurements.

  11. Hypersensitivity Reaction to Insulin Glargine and Insulin Detemir in a Pediatric Patient: A Case Report.

    PubMed

    Badik, Jennifer; Chen, Jimmy; Letvak, Kira; So, Tsz-Yin

    2016-01-01

    Allergy to human insulin or its analogs is rare, but it is still a significant issue in current diabetes care. Allergic reactions can range from localized injection site reactions to generalized anaphylaxis, and they can be caused by excipients or the insulin molecules themselves. We presented a case of a 14-year-old male patient with generalized allergic reactions to insulin glargine and insulin detemir. The patient was successfully managed by being switched to a continuous subcutaneous insulin infusion with insulin aspart. Allergic reactions to insulin detemir and insulin glargine have both been well described, with insulin detemir allergy appearing to be more common. There are several potential mechanisms for insulin allergy, and immunologic characteristics vary among different insulin analogs. After confirming insulin allergy in practice, management involves treating symptoms and switching insulin preparations. This is the first documented case of allergies to both insulin glargine and insulin detemir in a pediatric patient. Exact mechanism of insulin allergy is unknown, and management strategies must be individualized for each patient. PMID:26997933

  12. Hypersensitivity Reaction to Insulin Glargine and Insulin Detemir in a Pediatric Patient: A Case Report

    PubMed Central

    Badik, Jennifer; Chen, Jimmy; Letvak, Kira

    2016-01-01

    Allergy to human insulin or its analogs is rare, but it is still a significant issue in current diabetes care. Allergic reactions can range from localized injection site reactions to generalized anaphylaxis, and they can be caused by excipients or the insulin molecules themselves. We presented a case of a 14-year-old male patient with generalized allergic reactions to insulin glargine and insulin detemir. The patient was successfully managed by being switched to a continuous subcutaneous insulin infusion with insulin aspart. Allergic reactions to insulin detemir and insulin glargine have both been well described, with insulin detemir allergy appearing to be more common. There are several potential mechanisms for insulin allergy, and immunologic characteristics vary among different insulin analogs. After confirming insulin allergy in practice, management involves treating symptoms and switching insulin preparations. This is the first documented case of allergies to both insulin glargine and insulin detemir in a pediatric patient. Exact mechanism of insulin allergy is unknown, and management strategies must be individualized for each patient. PMID:26997933

  13. Continuous intravenous infusion of enfuvirtide in a patient with a multidrug-resistant HIV strain.

    PubMed

    Neijzen, Robert W; Van Maarseveen, Erik M; Hoepelman, Andy I M; Wensing, Annemarie M J; Bonora, Stefano; D'Avolio, Antonio; Mudrikova, Tania

    2016-08-01

    Case description To evaluate whether continuous intravenous (i.v.) administration of enfuvirtide (T20) could be a suitable alternative to subcutaneous (s.c.) administration of T20 in a patient with extensively drug-resistant HIV experiencing difficulties administering T20 subcutaneously. T20 was administered to a patient through 100 mL cassettes once daily via a CADD. Plasma samples were drawn and the pharmacokinetic profile compared to that of s.c. twice daily administration of T20. Also, viral replication and CD4+ count were monitored over a period of 9 months for this study. Continuous i.v. administration of T20 resulted in significantly higher T20 plasma levels compared to s.c. administration, continued viral suppression, a rise in CD4+ count and strong patient preference over s.c. administration. Conclusion This method of T20 administration may be a suitable alternative for selected patients who are not able to tolerate it when given subcutaneously. It may even be considered a priori in selected patients with extensive viral resistance who are unable or unwilling to inject T20 subcutaneously. PMID:27180258

  14. Postoperative analgesia in children: a prospective study in intermittent intramuscular injection versus continuous intravenous infusion of morphine.

    PubMed

    Hendrickson, M; Myre, L; Johnson, D G; Matlak, M E; Black, R E; Sullivan, J J

    1990-02-01

    Few advancements in postoperative pain control in children have been made despite longstanding inadequacies in conventional intramuscular analgesic regimens. While overestimating narcotic complication rates, physicians often underestimate efficacious doses, nurses are reluctant to give injections, and many children in pain shy away from shots. This study prospectively focuses on the safety, efficacy, and complication rate of intermittent intramuscular (IM) versus continuous intravenous infusion (IV) of morphine sulfate (MS) in 46 nonventilated children following major chest, abdominal, or orthopedic surgical procedures. Twenty patients assigned to the IM group had a mean age of 6.17 years and a mean weight of 23.0 kg. Twenty-six patients assigned to the IV group had a mean age of 8.74 years and a mean weight of 27.4 kg. The mean IM MS dose was 12.3 micrograms/kg/h while the mean IV dose was 19.8 micrograms/kg/h (P less than .001). Postoperative pain was assessed with a linear analogue scale from 1 to 10 (1, "doesn't hurt"; 10, "worst hurt possible") for 3 days following operation. Using the analysis of covariance (ANACOVA), nurse, parent, and patient mean pain scores in the IV group were significantly lower than those of the IM group when controlled for age, MS dose, and complications (P less than .007). Nurse assessment of pain correlated well with the patient and parent assessments (Pearson correlation coefficients greater than 0.6). Not only did IV infusion give better pain relief than IM injections, but there were no major complications such as respiratory depression. Minor complications in this study (nausea, urinary retention, drowsiness, vomiting, hallucinations, lightheadedness, and prolonged ileus) were not significantly different between IM and IV groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2303987

  15. Evaluation of the Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy for the Treatment of Advanced Pancreatic Carcinoma

    SciTech Connect

    Ikeda, O. Kusunoki, S.; Kudoh, K.; Takamori, H.; Tsuji, T.; Kanemitsu, K.; Yamashita, Y.

    2006-06-15

    Purpose. To evaluate the effects of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in patients with advanced pancreatic carcinoma. Methods. CTAI was performed in 17 patients with stage IV pancreatic cancer with (n = 11) or without (n = 6) liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The inferior pancreatic artery (IPA) was embolized to achieve delivery of the pancreatic blood supply through only the celiac artery. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. Treatment effects were evaluated based on the primary tumor size, liver metastasis, and survival time and factors such as tumor size, tumor location, and stage of pancreatic carcinoma; the embolized arteries were analyzed with respect to treatment effects and prognosis. Results. A catheter was fixed in the gastroduodenal artery and splenic artery in 10 and 7 patients, respectively. Complete peripancreatic arterial occlusion was successful in 10 patients. CT showed a decrease in tumor size in 6 of 17 (35%) patients and a decrease in liver metastases in 6 of 11 (55%) patients. The survival time ranged from 4 to 18 months (mean {+-} SD, 8.8 {+-} 1.5 months). Complete embolization of arteries surrounding the pancreas was achieved in 10 patients; they manifested superior treatment effects and prognoses (p < 0.05). Conclusion. In patients with advanced pancreatic cancer, long-term CTAI with systemic chemotherapy appeared to be effective not only against the primary tumor but also against liver metastases. Patients with successfully occluded peripancreatic arteries tended to survive longer.

  16. Combined hormonal infusion simulates the metabolic response to injury.

    PubMed Central

    Bessey, P Q; Watters, J M; Aoki, T T; Wilmore, D W

    1984-01-01

    To investigate the role of hormones as mediators of the metabolic response to injury, nine normal male volunteers received a continuous 74-hour infusion of the three 'stress' hormones: cortisol, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Diets were constant and matched on both occasions. Hormonal infusion achieved hormone concentrations similar to those seen following mild-moderate injury. With this alteration in the endocrine environment significant hypermetabolism, negative nitrogen and potassium balances, glucose intolerance, hyperinsulinemia, insulin resistance, sodium retention, and peripheral leukocytosis were observed. Additional studies with single hormone infusions indicated that these responses resulted from both additive and synergistic interactions of the hormones. Triple hormone infusion simulated many of the metabolic responses observed following mild-moderate injury and other catabolic illnesses. PMID:6431917

  17. Continuous water infusion enhances atmospheric pressure chemical ionization of methyl chloroformate derivatives in gas chromatography coupled to time-of-flight mass spectrometry-based metabolomics.

    PubMed

    Wachsmuth, Christian J; Dettmer, Katja; Lang, Sven A; Mycielska, Maria E; Oefner, Peter J

    2014-09-16

    The effects of continuous water infusion on efficiency and repeatability of atmospheric pressure chemical ionization of both methyl chloroformate (MCF) and methoxime-trimethylsilyl (MO-TMS) derivatives of metabolites were evaluated using gas chromatography-time-of-flight mass spectrometry. Water infusion at a flow-rate of 0.4 mL/h yielded not only an average 16.6-fold increase in intensity of the quasimolecular ion for 20 MCF-derivatized metabolite standards through suppression of in-source fragmentation but also the most repeatable peak area integrals. The impact of water infusion was the greatest for dicarboxylic acids and the least for (hetero-) aromatic compounds. Water infusion also improved the ability to detect reliably fold changes as small as 1.33-fold for the same 20 MCF-derivatized metabolite standards spiked into a human serum extract. On the other hand, MO-TMS derivatives were not significantly affected by water infusion, neither in their fragmentation patterns nor with regard to the detection of differentially regulated compounds. As a proof of principle, we applied MCF derivatization and GC-APCI-TOFMS to the detection of changes in abundance of metabolites in pancreatic cancer cells upon treatment with 17-DMAG. Water infusion increased not only the number of metabolites identified via their quasimolecular ion but also the reproducibility of peak areas, thereby almost doubling the number of significantly regulated metabolites (false discovery rate < 0.05) to a total of 23. PMID:25152309

  18. Perioperative continuous peripheral nerve blocks with disposable infusion pumps in children: a prospective descriptive study.

    PubMed

    Dadure, Christophe; Pirat, Philippe; Raux, Olivier; Troncin, Rachel; Rochette, Alain; Ricard, Christine; Capdevila, Xavier

    2003-09-01

    Continuous peripheral nerve blocks (CPNB) after pediatric major orthopedic surgery are not widely used. We conducted a prospective descriptive study to evaluate the effectiveness of disposable elastomeric pumps for CPNB in children. After inducing general anesthesia, 25 consecutive children scheduled for major orthopedic surgery received a 0.5-mL/kg bolus of a mixture of 1% lidocaine with epinephrine and 0.25% bupivacaine in axillary, femoral, or popliteal catheters. After surgery, disposable pumps with 0.2% ropivacaine were connected. Pump flows were adjusted to the patient's weight. Postoperative pain was evaluated using a visual analog scale or Children and Infants Postoperative Pain Scale scores at H1, H6, H12, H24, and H48, as well as amounts of rescue analgesia, adverse events, and motor and sensory block. An ambulation score for the children was also evaluated. Eleven popliteal, nine femoral, and five axillary continuous blocks were performed. All the blocks were effective for surgery. The mean total dose consumption of 0.2% ropivacaine was 10.1 mg/kg. Disposable pump flow varied from -9.61% to +8.6% compared with the theoretical one. Postoperative analgesia was excellent. The median of pain score was zero at each period studied. Sensory and motor block were noted at H1 and decreased from the sixth hour. No adverse events were noted. We concluded that the use of elastomeric disposable pumps for CPNB in children was an effective technique. PMID:12933385

  19. 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.

  20. Vinblastine plus bleomycin continuous infusion chemotherapy of stage III testicular carcinomas.

    PubMed

    Monfardini, S; Fossati, V; Pizzocaro, G; Villa, E

    1981-01-01

    Thirty-four consecutive patients with stage III testicular carcinomas were treated with vinblastine, 8 mg/m2 given in 2 fractions on day 1 and 2, followed by continuous intravenous administration of bleomycin, 15 mg/m2 in 1000 cc of 5% glucose and distilled water over a 24-hour period for 5 successive days beginning on day 2. This cycle was repeated every 28-35 days as toxicity permitted. Complete remission occurred in 18% and complete plus partial remission in 79%. Only 2 of 22 patients with advanced abdominal disease achieved a complete remission. After cytoreductive surgery the complete remission rate was increased to 39%. Median survival of complete responders at 3 years has not been reached, and it has been shown to be significantly superior to that of partial (p less than 0.01) and nonresponders (p less than 0.01). Toxic effects consisted mainly in severe leukopenia, stomatitis, adynamic ileum and osteoarticular pain. One drug-related death due to sepsis with agranulocytopenic fever was observed. Probably because of different patient selection, this report could not reproduce the results reported by Samuels et al. with equivalent drug dosage, but it was confirmed that this regimen is able to achieve a high overall response rate and a prolonged median survival in complete responders. The consistent success of this aggressive combination in inducing a high percentage of partial responses has opened the way for a better definition of the role of surgery for the treatment of advanced testicular carcinoma at out Institute. PMID:6167041

  1. The Effects of Anti-insulin Antibodies and Cross-reactivity with Human Recombinant Insulin Analogues in the E170 Insulin Immunometric Assay

    PubMed Central

    Kim, Serim; Hur, Mina; Moon, Hee Won; Kim, Jin Q

    2011-01-01

    Background Insulin assays are affected by varying degrees of interference from anti-insulin antibodies (IAs) and by cross-reactivity with recombinant insulin analogues. We evaluated the usefulness of the E170 insulin assay by assessing IA effects and cross-reactivity with 2 analogues. Methods Sera were obtained from 59 type 2 diabetes patients receiving continuous subcutaneous insulin infusion and 18 healthy controls. Insulin levels were determined using an E170 analyzer. To investigate the effects of IAs, we performed IA radioimmunoassays, and analyzed the differences between directly measured insulin (direct insulin) and polyethylene glycol (PEG)-treated insulins (free, IA-unbound; total, IA-bound and unbound insulin). We performed in-vitro cross-reactivity tests with insulin aspart and insulin glulisine. Results In IA-positive patients, E170 free insulin levels measured using the E170 analyzer were significantly lower than the direct insulin levels. The mean value of the direct/free insulin ratio and IA-bound insulin, which were calculated as the difference between total and free insulin, increased significantly as endogenous IA levels increased. The E170 insulin assay showed low cross-reactivities with both analogues (< 0.7%). Conclusions IAs interfered with E170 insulin assay, and the extent of interference correlated with the IA levels, which may be attributable to the increase in IA-bound insulin, and not to an error in the assay. The E170 insulin assay may measure only endogenous insulin since cross-reactivity is low. Our results suggest that the measurement of free insulin after PEG pre-treatment could be useful for β cell function assessment in diabetic patients undergoing insulin therapy. PMID:21239867

  2. Co-infusion of autologous adipose tissue derived insulin-secreting mesenchymal stem cells and bone marrow derived hematopoietic stem cells: viable therapy for type III.C. a diabetes mellitus.

    PubMed

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L

    2013-01-01

    Transition from acute pancreatitis to insulin-dependent diabetes mellitus (IDDM) is a rare manifestation of primary hyperparathyroidism caused by parathyroid adenoma because of impaired glucose tolerance and suppresses insulin secretion. We report the case of a 26-year-old male with pancreatic diabetes caused by parathyroid adenoma induced chronic pancreatitis. He had serum C-peptide 0.12 ng/ml, glutamic acid decarboxylase antibody 5.0 IU/ml, and glycosylated hemoglobin (HbA1C) 8.9%, and required 72 IU/day of biphasic-isophane insulin injection for uncontrolled hyperglycemia. We treated him with his own adipose tissue derived insulin-secreting mesenchymal stem-cells (IS-ADMSC) along with his bone marrow derived hematopoietic stem cells (BM-HSC). Autologous IS-ADMSC + BM-HSC were infused into subcutaneous tissue, portal and thymic circulation without any conditioning. Over a follow-up of 27 months, the patient is maintaining fasting and postprandial blood sugar levels of 132 and 165 mg/dl, respectively, with HbA1C 6.8% and requiring 36 IU/day of biphasic-isophane insulin. Co-infusion of IS-ADMSC + BM-HSC offers a safe and viable therapy for type III.C.a Diabetes Mellitus. PMID:24385073

  3. A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

    PubMed Central

    Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

    2015-01-01

    Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models

  4. Coronary artery bypass grafting in a patient with hemophilia B: continuous recombinant factor IX infusion as per the Japanese guidelines for replacement therapy.

    PubMed

    Suzuki, Tomoyuki; Kawamoto, Shunsuke; Kumagai, Kiichiro; Adachi, Osamu; Kanda, Keisuke; Ishikawa, Masaaki; Okitsu, Yoko; Harigae, Hideo; Kurosawa, Shin; Saiki, Yoshikatsu

    2016-08-01

    We herein report our experience of successfully managing the hemostatic system by controlling serum factor IX levels throughout the perioperative period in a patient with hemophilia B. Coronary artery bypass grafting with cardiopulmonary bypass was planned for a 52-year-old man with moderate severity of hemophilia B. During surgery, recombinant factor IX (rFIX; BeneFIX(®) Pfizer Japan inc., Tokyo, Japan) was administered by bolus infusion followed by continuous infusion as per the guidelines of the Japanese Society on Thrombosis and Hemostasis. The operative course was uneventful without any considerable bleeding or complications. PMID:25523881

  5. Efficacy of famotidine in patients with acute gastric mucosal injury after continuous infusion of cisplatin plus vindesine.

    PubMed

    Mori, K; Tominaga, K; Yokoyama, K; Suga, Y; Kishiro, I; Tsurui, M

    1995-01-01

    The effect of famotidine (H2 blocker) on the gastroduodenal mucosal injury induced by chemotherapy in non-small-cell lung cancer patients was prospectively evaluated from the clinical and endoscopic findings obtained in a randomized double-blind study. The patients, who were administered cisplatin (25 mg/m2/day, continuous infusion, days 1-5) and vindesine (3 mg/m2, bolus, days 1 and 8), were randomized into two groups, those administered famotidine (40 mg/day, oral) and those administered the placebo. The patients were examined by gastroduodenoscopy within 7 days before and after chemotherapy. There were 27 patients in the famotidine group and 28 patients in the placebo group. The gastric mucosal score after chemotherapy was significantly lower in the famotidine group than in the placebo group (P < 0.01), and in the 42 patients without symptoms than in the 13 patients (placebo group: 8, famotidine group: 5) with upper gastrointestinal symptoms (P < 0.01). The pH of the gastric juice after the chemotherapy significantly decreased in the placebo group (P < 0.05), and was significantly lower in the placebo group than in the famotidine group (P = 0.01). The co-administration of famotidine was effective in the prevention and control of chemotherapy-induced gastric mucosal injury. PMID:7797602

  6. Anti-Pseudomonas activity in bronchial secretions of patients receiving amikacin or tobramycin as a continuous infusion.

    PubMed Central

    Mombelli, G; Coppens, L; Thys, J P; Klastersky, J

    1981-01-01

    The penetration of amikacin and tobramycin into bronchial secretions and the resulting anti-Pseudomonas activity were assessed in two groups of tracheostomized or intubated patients with tracheobronchial infection and purulent bronchial secretions. The aminoglycosides were administered as continuous, high-dose intravenous infusions. The mean drug concentrations in serum and bronchial secretions were 12.8 and 2.0 microgram/ml for amikacin and 3.6 and 0.7 microgram/ml for tobramycin. The bronchial secretion/serum ratios varied over a wide range: from 9.6 to 22.8% (average, 14.9%) for amikacin and from 3 to 39.3% (average, 17.5%) for tobramycin. Sustained anti-Pseudomonas activities in bronchial secretions were achieved only in patients with very high aminoglycoside levels in serum. In most patients, however, no anti-Pseudomonas activity could be detected within bronchial secretions despite therapeutic levels of amikacin and tobramycin and adequate bactericidal activities in serum. PMID:7247362

  7. Effects of continuous rate intravenous infusion of butorphanol on physiologic and outcome variables in horses after celiotomy.

    PubMed

    Sellon, Debra C; Roberts, Malcolm C; Blikslager, Anthony T; Ulibarri, Catherine; Papich, Mark G

    2004-01-01

    A randomized, controlled, blinded clinical trial was performed to determine whether butorphanol administered by continuous rate infusion (CRI) for 24 hours after abdominal surgery would decrease pain and surgical stress responses and improve recovery in horses. Thirty-one horses undergoing exploratory celiotomy for abdominal pain were randomly assigned to receive butorphanol CRI (13 microg/kg/h for 24 hours after surgery; treatment) or isotonic saline (control). All horses received flunixin meglumine (1.1 mg/kg IV q12h). There were no significant differences between treatment and control horses in preoperative or operative variables. Treatment horses had significantly lower plasma cortisol concentration compared with control horses at 2, 8, 12, 24, 36, and 48 hours after surgery. Mean weight loss while hospitalized was significantly less for treatment horses than control horses, whether expressed as total decrease in body weight (13.9+/-3.4 and 27.9+/-4.5 kg, respectively) or as a percentage decrease in body weight (2.6+/-0.7 and 6.3+/-1.1%, respectively). Treatment horses were significantly delayed in time to first passage of feces (median times of 15 and 4 hours, respectively). Treatment horses had significantly improved behavior scores during the first 24 hours after surgery, consistent with the conclusion that they experienced less pain during that time. Butorphanol CRI during the immediate postoperative period significantly decreased plasma cortisol concentrations and improved recovery characteristics in horses undergoing abdominal surgery. PMID:15320598

  8. IT infusion

    NASA Technical Reports Server (NTRS)

    Feather, M. S.

    2002-01-01

    Infusing IT technology is a perennial challenge. The Technology Infusion and Maturity Assessment approach of Cornford & Hicks is shown applied to an example of IT infusion: moedl-based V&V of spacecraft software.

  9. Inhaled insulin: A “puff” than a “shot” before meals

    PubMed Central

    Brashier, Dick B. S.; Khadka, Anjan; Anantharamu, Tejus; Sharma, Ashok Kumar; Gupta, A. K.; Sharma, Sushil; Dahiya, N.

    2015-01-01

    Diabetes is a metabolic disorder characterized by relative or absolute deficiency of insulin, resulting in hyperglycemia. The main treatment of diabetes relies on subcutaneous insulin administration by injection or continuous infusion to control glucose levels, besides oral hypoglycemic agents for type 2 diabetes. Novel routes of insulin administration are an area of research in the diabetes field as insulin injection therapy is burdensome and painful for many patients. Inhalational insulin is a potential alternative to subcutaneous insulin in the management of diabetes. The large surface area, good vascularization, immense capacity for solute exchange and ultra-thinness of the alveolar epithelium facilitates systemic delivery of insulin via pulmonary administration. Inhaled insulin has been recently approved by Food and Drug Administration (FDA). It is a novel, rapid-acting inhaled insulin with a pharmacokinetic profile that is different from all other insulin products and comparatively safer than the previous failed inhaled insulin (Exubera). PMID:26311994

  10. Preoperative concurrent radiation therapy and cisplatinum continuous infusion in IIIa (N2) non small cell lung cancer. A pilot study.

    PubMed

    Maggi, G; Casadio, C; Cianci, R; Oliaro, A; Molinatti, M; Bretti, S; Clerico, M; Boidi-Trotti, A; Rovea, P

    1994-08-01

    From April 1991 to September 1993, 18 patients affected by a presumed operable IIIa (N2) non small cell lung cancer (NSCLC) with histologically confirmed bulky mediastinal metastases, received preoperative concurrent radiation therapy and continuous infusion of cisplatinum (CDDP). The radiotherapy consisted of 2 Gy given 5 days a week for a total dose of 50 Gy; CDDP was administered by means of a central catheter and a portable pump at the daily dose of 6 mg/m2 given on the same days as the radiation therapy (total dose: 150 mg/m2). Two weeks after the end of the treatment, the patients were reevaluated: 5 patients had either local or distant disease progression, the other 13 were submitted to thoracotomy: 12 received a complete resection and 1 patient underwent only a mediastinal lymphadenectomy, because pneumonectomy was impossible due to lack of respiratory function. No histological evidence of cancer cells was observed in the specimens of 6 patients (33%). Radiological response rate was 61% (11/18); resection rate was 66% (12/18) and complete resection rate was 61% (11/18). There was one postoperative death (5%). The 3 year actuarial survival rate is 63.6% for the patients who received a resection with a median survival time of 18 months. All non operated patients died within one year. Combined preoperative treatment was well tolerated. Better results were achieved in patients with squamous cell carcinoma who had a complete resection following a total tumor sterilization with radio-chemotherapy. PMID:7929550

  11. A randomized study of inpatient versus outpatient continuous infusion chemotherapy for patients with locally advanced head and neck cancer.

    PubMed

    Vokes, E E; Schilsky, R L; Choi, K E; Magid, D M; Guarnieri, C M; Whaling, S M; Ratain, M J; Weichselbaum, R R; Panje, W R

    1989-01-01

    This study was designed to evaluate the safety, reliability, and patient acceptance of outpatient continuous intravenous infusion (CVI) chemotherapy. Twenty-two patients with locally advanced head and neck cancer received induction chemotherapy with methotrexate, cisplatin and a 5-day CVI of 5-fluorouracil (5-FU). Patients were randomized to receive the 5-FU portion of cycle 1 either by a standard inpatient CVI chemotherapy delivery device (standard pump) or by the Infusor (Baxter Healthcare Corporation, Deerfield, IL), a portable chemotherapy delivery system that provides a constant flow of drug over a period of 24 hours. For cycle 2, patients crossed over to the alternative drug delivery method. Patients receiving chemotherapy via the Infusor could choose to be either inpatients or outpatients. Daily plasma concentrations of 5-FU were determined during the first two cycles of chemotherapy. There was no significant difference in the mean steady state plasma 5-FU levels achieved with either drug delivery method (329.7 +/- 95.8 ng/ml for infusor cycles vs. 352.8 +/- 114.9 ng/ml for standard pump cycles). Clinical toxicities consisted primarily of mucositis for both methods of drug delivery. Eight patients declined to receive CVI chemotherapy as outpatients citing as reasons fear of malfunction of the device, inconvenience of the frequent clinic visits necessitated by daily monitoring of plasma 5-FU concentrations, and restrictions in daily home activities. Eleven patients underwent CVI chemotherapy via Infusor as outpatients. All reported outpatient CVI chemotherapy as convenient and effective and, when eligible, chose it again in subsequent cycles. A comparison of estimated costs revealed reductions in daily costs of +366.00 (+2,200.00 per cycle) for outpatient chemotherapy. Outpatient CVI chemotherapy is a reliable drug delivery method that was accepted by a majority of patients in this study. These factors may help to establish outpatient CVI chemotherapy as a

  12. Direct infusion of a variant of insulin-like growth factor-I into the skin of sheep and effects on local blood flow, amino acid utilization and cell replication.

    PubMed

    Harris, P M; McBride, B W; Gurnsey, M P; Sinclair, B R; Lee, J

    1993-12-01

    In vivo effects of local infusion of a variant of insulin-like growth factor-I (IGF-I), long-R3-IGF-I, into the skin were investigated using six conscious sheep with food available ad libitum. An artery and vein on the abdominal flank of each animal, as well as the saphenous artery, were catheterized so that infusion of isotopically labelled amino acids, with or without IGF-I, could be used to determine amino acid uptake by arteriovenous difference in combination with blood flow determined by dye dilution. Measurements were made on each animal prior to IGF-I infusion, at hourly intervals for the 4 h of IGF-I infusion into the skin artery, then 2 and 4 h after IGF-I infusion ceased. Numbers of cells replicating in the bulbs of wool follicles in the IGF-I-infused area and in the skin on the contralateral side of each animal were measured after labelling with 5-bromo-2'-deoxyuridine. IGF-I caused a significant increase in the skin blood flow (P < 0.05), utilization of oxygen (P < 0.05), uptake of cysteine (P < 0.05) and phenylalanine (P < 0.001), and the rate of utilization of cysteine (P < 0.05) for protein synthesis. IGF-I increased amino acid uptake regardless of whether the skin was in negative or positive amino acid balance prior to infusion. During the recovery period amino acid utilization by skin returned towards preinfusion levels. No effects of IGF-I were found on replicating cell numbers in the bulbs of wool follicles. PMID:8133213

  13. A Comparison of Differences Between the Systemic Pharmacokinetics of Levobupivacaine and Ropivacaine During Continuous Epidural Infusion: A Prospective, Randomized, Multicenter, Double-Blind Controlled Trial

    PubMed Central

    Cusato, Maria; Ingelmo, Pablo; Niebel, Thekla Larissa; Somaini, Marta; Riva, Francesca; Tinelli, Carmine; De Andrés, José; Fanelli, Guido; Braschi, Antonio; Regazzi, Mario; Allegri, Massimo

    2015-01-01

    BACKGROUND: Epidural infusion of levobupivacaine and ropivacaine provides adequate postoperative pain management by minimizing side effects related to IV opioids and improving patient outcome. The safety profile of different drugs can be better estimated by comparing their pharmacokinetic profiles than by considering their objective side effects. Because levobupivacaine and ropivacaine have different pharmacokinetic properties, our aim was to investigate whether there is a difference in the pharmacokinetic variability of the 2 drugs in a homogeneous population undergoing continuous epidural infusion. This double-blind, multicenter, randomized, controlled trial study was designed to compare the pharmacokinetics of continuous thoracic epidural infusion of levobupivacaine 0.125% or ropivacaine 0.2% for postoperative pain management in adult patients who had undergone major abdominal, urological, or gynecological surgery. This study is focused on the evaluation of the coefficient of variation (CV) to assess the equivalence in the systemic exposure and interindividual variability between levobupivacaine and ropivacaine and, therefore, the possible differences in the predictability of the plasmatic concentrations of the 2 drugs during thoracic epidural infusion. METHODS: One hundred eighty-one adults undergoing major abdominal surgery were enrolled in the study. Patients were randomized to receive an epidural infusion of levobupivacaine 0.125% + sufentanil 0.75 μg/mL or of ropivacaine 0.2% + sufentanil 0.75 μg/mL at 5 mL/h for 48 hours. The primary end point of this study was to analyze the variability of plasma concentration of levobupivacaine and ropivacaine via an area under the curve within a range of 15% of the CV during 48 hours of continuous epidural infusion. The CV shows how the concentration values of local anesthetics are scattered around the median concentration value, thus indicating the extent to which plasma concentration is predictable during infusion

  14. [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. PMID:7968932

  15. Comparison of conventional dosing versus continuous-infusion vancomycin therapy for patients with suspected or documented gram-positive infections.

    PubMed Central

    James, J K; Palmer, S M; Levine, D P; Rybak, M J

    1996-01-01

    Ten patients were treated with conventional dosing (CD) and continuous-infusion (CI) vancomycin therapy in this prospective, randomized, crossover study. Patients were randomized to receive either CD or CI therapy for 2 consecutive days and then crossed over to receive the opposite regimen for 2 days. CD therapy consisted of 1 g of vancomycin every 12 h. CI therapy consisted of a 500-mg loading dose followed by 2 g infused over 24 h. Ten serum samples were obtained on the second day of each therapy for pharmacokinetic and pharmacodynamic analyses. Two clinical isolates of Staphylococcus aureus, one methicillin sensitive (MSSA 1199) and one methicillin resistant (MRSA 494), were chosen for pharmacodynamic evaluation of both regimens. The patient demographics (means +/- standard deviations [SD]) were as follows: sex, six males, four females; age, 36 +/- 11 years; and serum creatinine, 0.72 +/- 0.18 mg/dl. Mean pharmacokinetic parameters +/- SD for CD therapy were as follows: elimination rate constant, 0.16 +/- 0.07 h-1; half-life, 5.6 +/- 3.5 h; volume of distribution, 33.7 +/- 25 liters, 0.5 +/- 0.2 liters/kg; maximum concentration in serum, 53.4 +/- 19.3 micrograms/ml; and minimum concentration, 8.4 +/- 5.9 micrograms/ml. The steady-state concentration for CI was 20.2 +/- 11.1 micrograms/ml. Overall, both regimens resulted in the MIC being exceeded 100% of the time. The mean CD trough serum bactericidal titer (SBT) was 1:8, and the average CI SBTs were 1:16 for both isolates. Even though there was no statistically significant difference between CD trough and CI SBTs, the CI SBTs remained > 1:8 for 100% of the time versus 60% of the time for CD therapy. During CI therapy, 20 and 40% of the patients maintained SBTs of > 1:32 throughout the dosing interval for MSSA 1199 and MRSA 494, respectively. During CD therapy, however, only 10% of patients maintained SBTs of > 1:32 during the entire dosing interval for both isolates. The mean areas under the bactericidal titer

  16. How To Minimize Toxic Exposure to Pyridine during Continuous Infusion of Ceftazidime in Patients with Cystic Fibrosis?

    PubMed Central

    Amin, A.; Dupont, C.; Abely, M.; Desmazes-Dufeu, N.; Dubus, J. C.; Jouani, B.-L.; Merlette, C.; Nové-Josserand, R.; Pages, J.; Panzo, R.; Vidal, F.; Voge, F.; Hubert, D.

    2014-01-01

    Ceftazidime is particularly efficient against Pseudomonas aeruginosa in cystic fibrosis patients. Thus, the spontaneous production of pyridine, which is a toxic product, raises some concern. Our aim was to examine the kinetics of degradation of ceftazidime in portable infusion pumps either at 4°C, 22°C, or 33°C and to propose some recommendations in order to reduce the pyridine exposure. Two administration models were studied in vitro. In model 1, we administered 12 g of ceftazidime infused over 23 h (once-daily infusion) compared to 6 g infused over 11.5 h in model 2 (twice-daily regimen). Samples were collected at 0 h and then every 4 and 2 h after the shaping of portable infusion pumps in models 1 and 2, respectively. Both ceftazidime and pyridine were analyzed using an ultraviolet high-performance liquid chromatograph. Production of pyridine is highly depending on the temperature. The in situ production of pyridine per day of treatment decreases at a ratio close to 1/6 and 1/3 between 33°C and 4°C in models 1 and 2, respectively. Regardless of the conditions, the production of pyridine is significantly lower in model 2, whereas the total delivery amount of ceftazidime is significantly higher at 4°C and 33°C compared to that in model 1. According to a the precautionary principle, these findings lead to three major recommendations: (i) exposing a solution of ceftazidime to over 22°C should be strictly avoided, (ii) a divided dose of 6 g over 11.5 h instead of a once-daily administration is preferred, and (iii) infusion should be administered immediately after reconstitution. PMID:24614367

  17. Very-low-dose continuous drip infusion of landiolol hydrochloride for postoperative atrial tachyarrhythmia in patients with poor left ventricular function.

    PubMed

    Morisaki, Akimasa; Hosono, Mitsuharu; Sasaki, Yasuyuki; Hirai, Hidekazu; Sakaguchi, Masanori; Nakahira, Atsushi; Seo, Hiroyuki; Suehiro, Shigefumi

    2012-06-01

    Three patients with poor left ventricular function (left ventricular ejection fraction <30 %) developed postoperative atrial tachyarrhythmia in intensive care. Case 1 was a 64-year-old man who underwent a modified Bentall procedure and mitral valve annuloplasty. Case 2 was a 63-year-old woman who underwent quintuple coronary artery bypass grafting. Case 3 was a 65-year-old man who underwent mitral valve replacement. Preoperative intra-aortic balloon pumping was required in Cases 2 and 3. Excellent heart rate control with no hemodynamic deterioration was achieved in all three cases by very-low-dose continuous drip infusion of landiolol hydrochloride (2-5 μg/kg/min). Very-low-dose continuous drip infusion of landiolol hydrochloride is a safe and useful alternative for the control of perioperative atrial tachyarrhythmias in patients with poor left ventricular function. PMID:22566247

  18. Risk of transient hyperammonemic encephalopathy in cancer patients who received continuous infusion of 5-fluorouracil with the complication of dehydration and infection.

    PubMed

    Liaw, C C; Wang, H M; Wang, C H; Yang, T S; Chen, J S; Chang, H K; Lin, Y C; Liaw, S J; Yeh, C T

    1999-03-01

    From 1986 to 1998, 29 cancer patients who had 32 episodes of transient hyperammonemic encephalopathy related to continuous infusion of 5-fluorouracil (5-FU) were identified. None of the patients had decompensated liver disease. Onset of hyperammonemic encephalopathy varied from 0.5 to 5 days (mean: 2.6 +/- 1.3 days) after the initiation of chemotherapy. Plasma ammonium level ranged from 248 to 2387 microg% (mean: 626 +/- 431 microg%). Among the 32 episodes, 26 (81%) had various degrees of azotemia, 18 (56%) occurred during bacterial infections and 14 (44%) without infection occurred during periods of dehydration. Higher plasma ammonium levels and more rapid onset of hyperammonemia were seen in 18 patients with bacterial infections (p=0.003 and 0.0006, respectively) and in nine patients receiving high daily doses (2600 or 1800 mg/m2) of 5-FU (p=0.0001 and < 0.0001, respectively). In 25 out of 32 episodes (78%), plasma ammonium levels and mental status returned to normal within 2 days after adequate management. In conclusion, hyperammonemic encephalopathy can occur in patients receiving continuous infusion of 5-FU. Azotemia, body fluid insufficiency and bacterial infections were frequently found in these patients. It is therefore important to recognize this condition in patients receiving continuous infusion of 5-FU. PMID:10327032

  19. Population pharmacokinetics and exploratory pharmacodynamics of ifosfamide according to continuous or short infusion schedules: an n = 1 randomized study

    PubMed Central

    Brain, Etienne G C; Rezai, Kevan; Lokiec, François; Gutierrez, Maya; Urien, Saïk

    2008-01-01

    AIMS To model the pharmacokinetics and pharmacodynamics of ifosfamide and its key metabolites. The pharmacodynamic parameters included were renal toxicity and myelosuppression measured using urinary β2-microglobulin (BMG) and absolute neutrophil count (ANC), respectively. METHODS Seventeen patients were enrolled into an n = 1 randomized trial during two consecutive cycles of ifosfamide 9 g m−2 during each cycle given by a 3 h or 72 h infusion. Data were analyzed using NONMEM. RESULTS Ifosfamide and metabolite concentration–time profiles were described by a one-compartment open-model with auto-induction of clearance. BMG and ANC time-courses were related to ifosfamide concentration via indirect response models. CONCLUSIONS This modelling allowed the simulation of weekly schedules of flat doses with favourable myelotoxic profiles. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT The optimal infusion duration for ifosfamide remains to be determined.No differences according to time of infusion have been identified in traditional pharmacokinetic endpoints, such as area under the curve.The impact on pharmacodynamics has never been modelled or correlated with pharmacokinetics. WHAT THIS STUDY ADDS The pharmacokinetics and pharmacodynamics of ifosfamide and its main metabolites can both be modelled with no influence of infusion duration.Pharmacodynamic modelling (renal and haematological toxicity) allows further simulations of new schedules with favourable toxicity profiles. PMID:18294323

  20. Ultrasound-Guided Transversus Abdominis Plane Block versus Continuous Wound Infusion for Post-Caesarean Analgesia: A Randomized Trial

    PubMed Central

    Chandon, Michel; Bonnet, Agnès; Burg, Yannick; Barnichon, Carole; DesMesnards-Smaja, Véronique; Sitbon, Brigitte; Foiret, Christine; Dreyfus, Jean-François; Rahmani, Jamil; Laloë, Pierre-Antoine; Fischler, Marc; Le Guen, Morgan

    2014-01-01

    Objective To compare the analgesic effect of ultrasound-guided Transversus Abdominis Plane (TAP) block versus Continuous Wound Infusion (CWI) with levobupivacaine after caesarean delivery. Methods We recruited parturients undergoing elective caesareans for this multicenter study. Following written informed consent, they received a spinal anaesthetic without intrathecal morphine for their caesarean section. The postoperative analgesia was randomized to either a bilateral ultrasound guided TAP block (levobupivicaine = 150 mg) or a CWI through an elastomeric pump for 48 hours (levobupivacaine = 150 mg the first day and 12.5 mg/h thereafter). Every woman received regular analgesics along with oral morphine if required. The primary outcome was comparison of the 48-hour area under the curve (AUC) pain scores. Secondary outcomes included morphine consumption, adverse events, and persistent pain one month postoperatively. Results Recruitment of 120 women was planned but the study was prematurely terminated due to the occurrence of generalized seizures in one patient of the TAP group. By then, 36 patients with TAP and 29 with CWI had completed the study. AUC of pain at rest and during mobilization were not significantly different: 50 [22.5–80] in TAP versus 50 [27.5–130] in CWI (P = 0.4) and 190 [130–240] versus 160 [112.5–247.5] (P = 0.5), respectively. Morphine consumption (0 [0–20] mg in the TAP group and 10 [0–32.5] mg in the CWI group (P = 0.09)) and persistent pain at one month were similar in both groups (respectively 29.6% and 26.6% (P = 0.73)). Conclusion In cases of morphine-free spinal anesthesia for cesarean delivery, no difference between TAP block and CWI for postoperative analgesia was suggested. TAP block may induce seizures in this specific context. Consequently, such a technique after a caesarean section cannot be recommended. Trial Registration ClinicalTrials.gov NCT01151943 PMID:25093663

  1. A Pilot Study of Continuous Infusion of Mycophenolate Mofetil for Prophylaxis of Graft-versus-Host-Disease in Pediatric Patients.

    PubMed

    Windreich, Randy M; Goyal, Rakesh K; Joshi, Rujuta; Kenkre, Tanya S; Howrie, Denise; Venkataramanan, Raman

    2016-04-01

    Mycophenolate mofetil (MMF), an ester prodrug of mycophenolic acid (MPA), is used increasingly for graft-versus-host disease (GVHD) prophylaxis. Empiric fixed-dose-escalation strategies in pediatric hematopoietic cell transplantation (HCT) recipients have failed to achieve target MPA exposure. We evaluated the safety and feasibility of a pharmacokinetics-based dosing approach using a novel continuous infusion (CI) method of administration of MMF in pediatric HCT recipients. All patients received a myeloablative conditioning with cyclosporine A and MMF for GVHD prophylaxis. MMF was initiated on day 0 at a dose of 15 mg/kg every 8 hours. Based on steady-state pharmacokinetics, MMF was converted to CI to target a total MPA AUC(0-24) of 40 to 80 μg·hour/mL. The MMF dose was adjusted to maintain a total MPA steady-state concentration (Css) of 1.7 to 3.3 μg/mL. During the CI schedule, MPA AUC(0-24) was maintained at a mean of 40.1 μg·hour/mL (range, 20.6 to 63.8), and 17 of 19 patients (89%) achieved MPA Css within target of 1.7 to 3.3 μg/mL. Eighteen of 19 patients (95%) achieved neutrophil engraftment at a median of 13 days (range, 8 to 41) post-transplant and platelet engraftment at 39 days (range, 17 to 298) days post-transplant. Six of 18 assessable patients (33%) developed stages II to IV acute GVHD and 2 of 15 (13%) developed chronic GVHD. The MMF dose was reduced in 9 patients due to gastrointestinal symptoms (n = 6), low blood counts (n = 4), and viral infection (n = 3). Five patients with acute lymphoblastic leukemia relapsed, of whom 4 have died. Fifteen of 19 patients are alive with a median follow-up of 2.4 years (range, .4 to 4.9), with 3-year event-free and overall survival rates of 68% and 79%, respectively. In this pilot study of pharmacokinetically directed MMF dosing, we observed no toxic deaths, excellent engraftment, and low rates of grades III to IV acute and chronic GVHD. We found significantly lower half-life and higher drug clearance in

  2. Labetalol infusion for refractory hypertension causing severe hypotension and bradycardia: an issue of patient safety.

    PubMed

    Fahed, Samir; Grum, Daniel F; Papadimos, Thomas J

    2008-01-01

    Incremental doses of intravenous labetalol are safe and effective and, at times, such therapy may need to be augmented by a continuous infusion of labetalol to control severe hypertension. Continuous infusions of labetalol may exceed the recommended maximum daily dose of 300 mg on occasion. We report a case in which hypertension occurring after an abdominal aortic aneurysm repair, initially responsive to intermittent intravenous beta-blockade, became resistant to this therapy leading to the choice of an intravenous labetalol infusion as the therapeutic option. The labetalol infusion resulted in a profound cardiovascular compromise in this postoperative critically ill patient. While infusions of labetalol have successfully been used, prolonged administration in the intensive care unit requires vigilance and the establishment of a therapeutic rationale/policy for interventions, such as the ready availability of glucagon, beta-agonists, phosphodiesterase inhibitors, insulin, and vasopressin when severe cardiovascular depression occurs. PMID:18505576

  3. Optimal dosing of antibiotics in critically ill patients by using continuous/extended infusions: a systematic review and meta-analysis

    PubMed Central

    2013-01-01

    Introduction The aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials, such as extended/continuous infusions, in critically ill patients is associated with improved outcomes as compared with traditional dosing methods. Methods We searched Medline, HealthStar, EMBASE, Cochrane Clinical Trial Registry, and CINAHL from inception to September 2013 without language restrictions for studies comparing the use of extended/continuous infusions with traditional dosing. Two authors independently selected studies, extracted data on methodology and outcomes, and performed quality assessment. Meta-analyses were performed by using random-effects models. Results Of 1,319 citations, 13 randomized controlled trials (RCTs) (n = 782 patients) and 13 cohort studies (n = 2,117 patients) met the inclusion criteria. Compared with traditional non-pharmacodynamic-based dosing, RCTs of continuous/extended infusions significantly reduced clinical failure rates (relative risk (RR) 0.68; 95% confidence interval (CI) 0.49 to 0.94, P = 0.02) and intensive care unit length of stay (mean difference, −1.5; 95% CI, −2.8 to −0.2 days, P = 0.02), but not mortality (RR, 0.87; 95% CI, 0.64 to 1.19; P = 0.38). No significant between-trial heterogeneity was found for these analyses (I2 = 0). Reduced mortality rates almost achieved statistical significance when the results of all included studies (RCTs and cohort studies) were pooled (RR, 0.83; 95% CI, 0.69 to 1.00; P = 0.054). Conclusions Pooled results from small RCTs suggest reduced clinical failure rates and intensive care unit length-of-stay when using continuous/extended infusions of antibiotics in critically ill patients. Reduced mortality rates almost achieved statistical significance when the results of RCTs were combined with cohort studies. These results support the conduct of adequately powered RCTs to define better the utility of continuous/extended infusions in the

  4. Comparison of the Effects of Subcutaneous Versus Continuous Infusion of Heparin on Key Inflammatory Parameters Following Sepsis

    PubMed Central

    Nouri, Masoumeh; Ahmadi, Arezoo; Etezadi, Farhad; Barzegar, Elchin; Mojtahedzadeh, Mojtaba

    2016-01-01

    Background Sepsis is the result of the interaction between inflammatory mediators and coagulation pathway. Unfractionated heparin may play a role as an anti-inflammatory agent beyond its anticoagulatory effect in sepsis. As a result, it may cause reduction in organ failure rate in patients with sepsis due to its impact on both inflammatory and coagulation process. Objectives The aim of this study was to evaluate the anti-inflammatory effects of heparin in sepsis. Plasma plasminogen activator inhibitor-1 (PAI-1) as an inflammatory mediator and urinary necoutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney injury were investigated. Patients and Methods This prospective, randomized controlled trial was conducted in a 32-bed intensive care unit. Thirty patients with sepsis were randomized to receive heparin infusion of 500 units/hour or 5000 units of heparin three times a day, subcutaneously. The plasma level of PAI-1 and urinary level of NGAL were determined at day 0, 2 and 7. Results The infusion group had a lower plasma PAI-1 level compared to the subcutaneous group at day 7 (11.3 ± 1.6 vs. 16.5 ± 4.2; P = 0.003). The urinary NGAL level was lower in the infusion group at day 2 (131.3 ± 11.9 vs. 151.2 ± 20.6; P = 0.014); however, at day 7 the NGAL level was decreased in the subcutaneous group as much as the infusion group and there was no significant difference between the two groups. There was no significant difference in the acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores between the two groups at day 0, 2 and 7. Conclusions Low-dose heparin infusion compared to subcutaneous heparin can decrease the plasma PAI-1 and urinary NGAL levels more rapidly. It can be related to anti-inflammatory effects of heparin, which may be more prominent in infusion route. PMID:27252904

  5. Prolonged blood pressure elevation following continuous infusion of angiotensin II-a baroreflex study in healthy humans.

    PubMed

    Sayk, Friedhelm; Wobbe, Isabel; Twesten, Christoph; Meusel, Moritz; Wellhöner, Peter; Derad, Inge; Dodt, Christoph

    2015-12-01

    ANG II interacts with the sympathetic nervous system at central nervous blood pressure-regulating structures, including the baroreflex. It is unknown whether prolonged BP elevation mediated by high ANG II plasma levels could induce a persistent shift of the central nervous baroreflex setpoint, lasting beyond the short ANG II plasmatic half time of a few seconds, thereby consolidating elevated BP and/or increased SNA in healthy humans. In a blinded crossover design, ANG II or placebo (saline) was infused for a 6-h period in 12 resting normotensive students (6 males, 6 females) raising BP to borderline hypertensive levels. Between 60 and 120 min after the infusion period, muscle sympathetic nerve activity (MSNA) was assessed microneurographically and correlated with oscillometric BP measurements and heart rate at supine rest (baseline) and during pharmacologic baroreceptor challenge. Infusion of ANG II increased BP to borderline-hypertensive levels, as intended, whereas heart rate remained unaltered. At baroreflex assessment (i.e., 60-120 min after end of infusion period), systolic BP was significantly higher compared with placebo (Δ8.4 ± 3.1 mmHg; P < 0.05), whereas diastolic values were nearly equal between conditions. Baseline MSNA was neither decreased nor increased, and baroreflex sensitivity to vasoactive drug challenge was not altered. Our results show that elevation of ANG II plasma levels over 6 h was able to increase systolic, but not diastolic, BP far beyond blood-mediated ANG II effects. MSNA or heart rate did not counter-regulate this BP elevation, indicating that ANG II had sustainably reset the central nervous BP threshold of sympathetic baroreflex function to accept elevated BP input signals without counter-regulatory response. PMID:26400183

  6. Review and update of insulin dependent diabetes mellitus.

    PubMed

    Gorrell, Jennifer Justice; Williams, Jennifer Schoelles; Powell, Paula

    2003-10-01

    The purpose of this article is to provide the health care practitioner with a comprehensive review of the pathophysiology and treatment of Type 1 Diabetes Mellitus. Traditionally, insulin has been administered via an insulin syringe. In the recent past, diabetes research has focused on developing more convenient insulin delivery devices and longer acting insulin's in hopes of increasing compliance with insulin therapy and improving the management of Type 1 diabetes in both children and adults. Rapidly developing approaches to insulin delivery for Type 1 diabetes continue to be developed at a rapid rate, including administration via continuous subcutaneous insulin infusion in addition to other new approaches. With these advances in therapy, pediatric patients with Type 1 diabetes have been able to achieve strict glycemic control, although the treatment of hypoglycemia remains a burden. The objectives of this article are to the following: to review the epidemiology, risk factors, pathophysiology, clinical manifestations, and diagnostic criteria of Type 1 diabetes mellitus in children,; to discuss the management of these patients, including, insulin therapy, monitoring, diet and exercise, carbohydrate counting and treatment of hypoglycemia,; and to review insulin administration devices, including insulin pens, insulin jet injectors, insulin pumps, and novel insulin delivery systems. PMID:23118681

  7. Infusion Extractor

    NASA Technical Reports Server (NTRS)

    Chang-Diaz, Franklin R.

    1988-01-01

    Apparatus and method of removing desirable constituents from an infusible material by infusion extraction, where a piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, and where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber.

  8. Combining insulins for optimal blood glucose control in type I and 2 diabetes: focus on insulin glulisine.

    PubMed

    Ulrich, Heather; Snyder, Benjamin; Garg, Satish K

    2007-01-01

    Normalization of blood glucose is essential for the prevention of diabetes mellitus (DM)-related microvascular and macrovascular complications. Despite substantial literature to support the benefits of glucose lowering and clear treatment targets, glycemic control remains suboptimal for most people with DM in the United States. Pharmacokinetic limitations of conventional insulins have been a barrier to achieving treatment targets secondary to adverse effects such as hypoglycemia and weight gain. Recombinant DNA technology has allowed modification of the insulin molecule to produce insulin analogues that overcome these pharmacokinetic limitations. With time action profiles that more closely mimic physiologic insulin secretion, rapid acting insulin analogues (RAAs) reduce post-prandial glucose excursions and hypoglycemia when compared to regular human insulin (RHI). Insulin glulisine (Apidra) is a rapid-acting insulin analogue created by substituting lysine for asparagine at position B3 and glutamic acid for lysine at position B29 on the B chain of human insulin. The quick absorption of insulin glulisine more closely reproduces physiologic first-phase insulin secretion and its rapid acting profile is maintained across patient subtypes. Clinical trials have demonstrated comparable or greater efficacy of insulin glulisine versus insulin lispro or RHI, respectively. Efficacy is maintained even when insulin glulisine is administered post-meal. In addition, glulisine appears to have a more rapid time action profile compared with insulin lispro across various body mass indexes (BMIs). The safety and tolerability profile of insulin glulisine is also comparable to that of insulin lispro or RHI in type 1 or 2 DM and it has been shown to be as safe and effective when used in a continuous subcutaneous insulin infusion (CSII). In summary, insulin glulisine is a safe, effective, and well tolerated rapid-acting insulin analogue across all BMIs and a worthy option for prandial

  9. BDNF, IGF-I, Glucose and Insulin during Continuous and Interval Exercise in Type 1 Diabetes.

    PubMed

    Tonoli, C; Heyman, E; Roelands, B; Buyse, L; Piacentini, F; Berthoin, S; Bailey, S; Pattyn, N; Meeusen, R

    2015-11-01

    Type 1 diabetes (T1D) can have a significant impact on brain function, mostly ascribed to episodes of hypoglycemia and chronic hyperglycemia. Exercise has positive effects on acute and chronic glycemic control in T1D, and has beneficial effects on cognitive function by increasing neurotrophins such as BDNF and IGF-I in non-diabetic humans. The present study examines the effects of different types of exercise intensities on neurotrophins in T1D. 10 participants with type 1 diabetes were evaluated in 3 sessions: high-intensity exercise (10×[60 s 90%Wmax, 60 s 50 W]), continuous exercise (22 min, 70% VO2 max) and a control session. Blood glucose, serum free insulin, serum BDNF and IGF-I were assessed pre/post all the trials and after recovery. Blood glucose significantly decreased after both exercise intensities and BDNF levels increased, with a dose-response effect for exercise intensity on BDNF. IGF-I changed over time, but without a difference between the different exercise protocols. Both exercise intensities change neurotrophins in T1D, but also exhibit a dose response effect for BDNF. The intensity-dependent findings may aid in designing exercise prescriptions for maintaining or improving neurological health in T1D, but both types of exercise can be implemented. PMID:26212245

  10. Continuous Glucose Monitoring in Insulin-Treated Patients in Non-ICU Settings

    PubMed Central

    Gomez, Ana Maria

    2014-01-01

    Inpatient hyperglycemia, in patients with and without a history of diabetes, is associated with increased risk of complications, mortality, and longer hospital stay in medicine and surgical patients. Bedside capillary point of care testing is widely recommended as the preferred method for glucose monitoring and for guiding glycemic management of individual patients; however, the accuracy of most handheld glucose meters is far from optimal. Recent studies in the hospital setting have reported that the use of continuous glucose monitoring (CGM) can provide real-time information about glucose concentration, direction, and rate of change over a period of several days. Because it provides glucose values every 5-10 minutes 24 hours a day, CGM may have an advantage over point of care testing with respect to reducing the incidence of severe hypoglycemia in acute care. Real-time CGM technology may facilitate glycemic control and to reduce hypoglycemia in insulin-treated patients. Recent guidelines, however, have recommended deferring the use of CGM in the adult hospital setting until further data on accuracy and safety become available. In this study, we review the advantages and disadvantages of the use of real-time CGM in the management of dysglycemia in the hospital setting. PMID:25125454

  11. Continuous glucose monitoring in insulin-treated patients in non-ICU settings.

    PubMed

    Gomez, Ana Maria; Umpierrez, Guillermo E

    2014-09-01

    Inpatient hyperglycemia, in patients with and without a history of diabetes, is associated with increased risk of complications, mortality, and longer hospital stay in medicine and surgical patients. Bedside capillary point of care testing is widely recommended as the preferred method for glucose monitoring and for guiding glycemic management of individual patients; however, the accuracy of most handheld glucose meters is far from optimal. Recent studies in the hospital setting have reported that the use of continuous glucose monitoring (CGM) can provide real-time information about glucose concentration, direction, and rate of change over a period of several days. Because it provides glucose values every 5-10 minutes 24 hours a day, CGM may have an advantage over point of care testing with respect to reducing the incidence of severe hypoglycemia in acute care. Real-time CGM technology may facilitate glycemic control and to reduce hypoglycemia in insulin-treated patients. Recent guidelines, however, have recommended deferring the use of CGM in the adult hospital setting until further data on accuracy and safety become available. In this study, we review the advantages and disadvantages of the use of real-time CGM in the management of dysglycemia in the hospital setting. PMID:25125454

  12. A phase II study of paclitaxel, weekly, 24-hour continuous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer

    PubMed Central

    Kollmannsberger, C; Quietzsch, D; Haag, C; Lingenfelser, T; Schroeder, M; Hartmann, J T; Baronius, W; Hempel, V; Clemens, M; Kanz, L; Bokemeyer, C

    2000-01-01

    To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel, cisplatin and 24 h continuous infusion of 5-FU/folinic acid in patients (pts) with unresectable, locally advanced or metastatic gastric adenocarcinoma. Forty-five chemotherapy-naive pts (28 male and 17 female) with a median age of 60 years (range 35–74) were enrolled. 5-FU 2 g/m2was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2as a 2 h infusion. Paclitaxel 175 mg/m2was administered as a 3 h-infusion on days 1 and 22 and cisplatin 50 mg/m2as 1 h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29, 36) followed by 2 weeks rest were considered one cycle. A median of 3 cycles (range 1–4) were administered to 45 pts assessable for response, survival and toxicity. Five pts (11%) obtained a CR and 18 pts (40%) a PR (ORR 51%; 95% Cl: 35.8–66.3%). Responses were achieved in the liver, lymph nodes, lungs and at the site of the primary tumour. Nine pts (20%) had stable disease. Thirteen pts (29%) were considered to have failed treatment, 8 pts (18%) due to progressive disease and 5 pts (11%) who did not receive one complete cycle of therapy due to acute non-haematologic toxicity. The median progression-free and overall survival times were 9 months (range 1–36+) and 14 months (range 2–36+), respectively. Neutropenia WHO III°/IV° occurred in 7 pts (15%) with only 1 pt having grade IV. Additional non-haematologic WHO III°/IV° toxicities included nausea/vomiting in 5 (11%), alopecia in 22 (49%), and diarrhoea in 1 patient each (2%). Dose reductions or treatment delays were necessary in 8 pts (17%), mainly due to neutropenia. All pts were treated on an outpatient basis. The combination of paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of pts with advanced gastric cancer. While the overall acceptable toxicity allows its use in the palliative setting, it may also be an attractive

  13. A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study

    PubMed Central

    Hunault-Berger, Mathilde; Leguay, Thibaut; Thomas, Xavier; Legrand, Ollivier; Huguet, Françoise; Bonmati, Caroline; Escoffre-Barbe, Martine; Legros, Laurence; Turlure, Pascal; Chevallier, Patrice; Larosa, Fabrice; Garban, Frederic; Reman, Oumedaly; Rousselot, Philippe; Dhédin, Nathalie; Delannoy, André; Lafage-Pochitaloff, Marina; Béné, Marie Christine; Ifrah, Norbert; Dombret, Hervé

    2011-01-01

    Background The prognosis of acute lymphoblastic leukemia in the elderly is poor. The GRAALL-SA1 phase II, randomized trial compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients 55 years or older with Philadelphia chromosome-negative acute lymphoblastic leukemia. Design and Methods Sixty patients received either continuous-infusion doxorubicin (12 mg/m2/day) and continuous-infusion vincristine (0.4 mg/day) on days 1–4 or pegylated liposomal doxorubicin (40 mg/m2) and standard vincristine (2 mg) on day 1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. End-points were safety, outcome and prognostic factors. Results Myelosuppression was reduced in the pegylated liposomal doxorubicin arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and fewer red blood cell transfusions (P=0.04). Grade 3/4 infections and Gram-negative bacteremia were reduced in the pegylated liposomal doxorubicin arm (P=0.04 and P=0.02, respectively). There was a trend towards fewer cardiac events among the patients who received pegylated liposomal doxorubicin (1/29 versus 6/31). The complete remission rate was 82% and, with a median follow-up of 4 years, median event-free survival and overall survival were 9 and 10 months, respectively. Despite the better tolerance of pegylated liposomal doxorubicin, no differences in survival were observed between the two arms, due to trends towards more induction refractoriness (17 versus 3%, P=0.10) and a higher cumulative incidence of relapse (52% versus 32% at 2 years, P=0.20) in the pegylated liposomal doxorubicin arm. Conclusions With the drug schedules used in this study, pegylated liposomal doxorubicin did not improve the outcome of elderly patients with acute lymphoblastic leukemia despite reduced toxicities. PMID:20971822

  14. 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

  15. Clinical Experience with Insulin Glargine in Type 1 Diabetes

    PubMed Central

    Moser, Emily; Dain, Marie-Paule; Rodionova, Anastasia

    2010-01-01

    Abstract The Diabetes Control and Complications Trial (DCCT) demonstrated the importance of optimal glycemic control achieved through intensive insulin therapy in reducing the microvascular complications associated with type 1 diabetes. However, the DCCT, which was conducted prior to the availability of insulin analogs, also reported a significant increase in severe hypoglycemia with intensive versus conventional therapy. Insulin analogs were developed to aid patients in achieving better diabetes control by providing insulins with optimized pharmacokinetic and pharmacodynamic characteristics. Insulin glargine was the first long-acting insulin analog with a 24-h duration of action, offering once-daily injection, and has now been in clinical use for over 10 years. The authors performed a systematic search of EMBASE, MEDLINE, and Web of Science (Science Citation Index) to determine the efficacy of insulin glargine in type 1 diabetes in basal–bolus insulin regimens. Randomized controlled trials have demonstrated that glycemic control with insulin glargine is at least comparable to that with neutral protamine Hagedorn (NPH) insulin in adults and in children and adolescents, and with continuous subcutaneous insulin infusion in adults. However, these same trials show a significantly lower risk for hypoglycemia with insulin glargine compared with NPH insulin in adults. PMID:20969435

  16. Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity.

    PubMed

    Caligiuri, M A; Murray, C; Soiffer, R J; Klumpp, T R; Seiden, M; Cochran, K; Cameron, C; Ish, C; Buchanan, L; Perillo, D

    1991-12-01

    In previous clinical trials, recombinant interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninefold increases, respectively, at these two dose levels) without any changes in B cells, T cells, neutrophils, or monocytes. Grade 2 toxicity was observed at the dose of 6.0 x 10(5) U/m2/d, as three patients required interruption of therapy and two patients who completed therapy developed transient hypothyroidism. In patients with increased NK cells, enhancement of non-major histocompatibility complex (MHC)-restricted cytotoxicity and increased generation of LAK cells in vitro were also demonstrated. Therapy with low-dose rIL-2 can be given safely in an uninterrupted fashion for prolonged periods of time in an outpatient setting. This results in selective expansion of NK cells in vivo with minimal toxicity. Further investigation of this schedule for immunomodulation in vivo should be pursued in phase II studies of both malignant and immunodeficient disease states. PMID:1960552

  17. Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach

    PubMed Central

    Viale, Pierluigi; Cojutti, Piergiorgio; Furlanut, Mario

    2012-01-01

    The worrisome increase in Gram-negative bacteria with borderline susceptibility to carbapenems and of carbapenemase-producing Enterobacteriaceae has significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CLCr) estimates for use in daily clinical practice to target the steady-state concentrations (Csss) of meropenem during continuous infusion at 8 to 16 mg/liter (after the administration of an initial loading dose of 1 to 2 g over 30 min). The correlation between meropenem clearance (CLm) and CLCr was retrospectively assessed in a cohort of critically ill patients (group 1, n = 67) to create a formula for dosage calculation to target Css. The performance of this formula was validated in a similar cohort (group 2, n = 56) by comparison of the observed and the predicted Csss. A significant relationship between CLm and CLCr was observed in group 1 (r = 0.72, P < 0.001). The application of the formula to meropenem dosing in group 2, infusion rate (g/24 h) = [0.078 × CLCr (ml/min) + 2.85] × target Css × (24/1,000), led to a significant correlation between the observed and the predicted Csss (r = 0.92, P < 0.001). Dosing nomograms based on CLCr were created to target the meropenem Css at 8, 12, and 16 mg/liter in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline susceptible pathogens or even of carbapenemase producers and/or of pathophysiological conditions which may enhance meropenem clearance. PMID:23045356

  18. Infusion extractor

    NASA Technical Reports Server (NTRS)

    Chang-Diaz, Franklin R. (Inventor)

    1986-01-01

    This invention relates to an apparatus and method of removing desirable constituents from an infusible material by infusion extraction. A piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber. The method is applicable to operation in low or micro-gravity environments.

  19. Prevention of central venous line-related thrombosis by continuous infusion of low-dose unfractionated heparin, in patients with haemato-oncological disease. A randomized controlled trial.

    PubMed

    Abdelkefi, Abderrahman; Ben Othman, Tarek; Kammoun, Leïla; Chelli, Mouna; Romdhane, Neïla Ben; Kriaa, Azza; Ladeb, Saloua; Torjman, Lamia; Lakhal, Amel; Achour, Wafa; Ben Hassen, Assia; Hsaïri, Mohamed; Ladeb, Fethi; Ben Abdeladhim, Abdeladhim

    2004-09-01

    We have conducted a prospective randomized controlled trial to evaluate the role of low-dose unfractionated heparin prophylaxis in preventing central venous line-related thrombosis in patients with haemato-oncological disease. Patients were randomly assigned to receive either prophylactic intravenous unfractionated heparin (continuous infusion of 100 IU/kg/daily) or 50 ml/daily of normal saline solution as a continuous infusion. CVLs were externalized, non tunneled, double lumen catheters. All CVLs were placed percutaneously by the same physician in the subclavian vein. Upper limb veins were systematically examined by ultrasonography just before, or <24 hours after, catheter removal, and in case of clinical signs of thrombosis. One hundred and twenty-eight CVLs were inserted. Catheter-related thrombosis occurred in 1.5% of the catheters inserted in patients of the heparin group, and in 12.6% in the control group (p = 0.03). No other risk factors were found for the development of catheter-related thrombosis. Two and three patients experienced severe bleeding in the heparin group, and in the control group, respectively (p = 0.18). There were no other side-effects clearly ascribable to the use of unfractionated heparin. This is the first prospective, randomized study, which shows that low-dose of unfractionated heparin is safe and effective to prevent catheter-related thrombosis in patients with haemato-oncological disease. PMID:15351864

  20. Use of insulin in diabetes: a century of treatment.

    PubMed

    Shahani, Savita; Shahani, Lokesh

    2015-12-01

    Insulin is a key player in the control of hyperglycaemia for patients with type 1 diabetes mellitus and selected patients with type 2 diabetes mellitus. There have been many advances in insulin drug delivery from its first administration as a crude pancreatic extract till today. The traditional and most predictable method for administration of insulin is by subcutaneous injection. Currently available insulin delivery systems include insulin syringes, infusion pumps, jet injectors, and pens. The major drawback of insulin therapy is its invasive nature. Non-invasive delivery of insulin has long been a major goal for the treatment of diabetes mellitus. Although there have been improvements in insulin therapy since it was first conceived, it is still far from mimicking the physiological secretion of pancreatic β-cells, and research to find new insulin formulations and new routes of administration continues. This article reviews the emerging technologies, including insulin inhalers, insulin buccal spray, insulin pill, islet cell transplant, and stem cell therapy, as treatment options for diabetes mellitus. PMID:26554270

  1. Long R3 insulin-like growth factor-I (IGF-I) infusion stimulates organ growth but reduces plasma IGF-I, IGF-II and IGF binding protein concentrations in the guinea pig.

    PubMed

    Conlon, M A; Tomas, F M; Owens, P C; Wallace, J C; Howarth, G S; Ballard, F J

    1995-08-01

    We have tested whether an animal with substantial amounts of both IGF-I and IGF-II in circulation, such as the guinea pig, would respond to chronic IGF infusion in the same manner as the adult rat, which has negligible amounts of IGF-II in blood. Female guinea pigs of 350 g body weight were continuously infused for 7 days with recombinant guinea pig IGF-I or -II (120 or 360 micrograms/day) or long R3 IGF-I (LR3IGF-I) (120 micrograms/day), an analogue which has much reduced affinities for IGF binding proteins. IGF-I or IGF-II infusion led to substantial increases in plasma IGF-I or IGF-II respectively in comparison with vehicle-infused animals. Nevertheless, body weight gain, feed intake, feed conversion efficiency and carcass composition were not significantly affected by any treatment (significance was deemed to be P < 0.05). Amongst the tissues examined only the fractional weight (g/kg body weight) of the adrenals was increased, and that only by the higher dose (360 micrograms/day) of IGF-I. However, the fractional weight of adrenals, gut, kidneys and spleen were significantly increased by LR3IGF-I, but again overall growth was not stimulated. A possible explanation for the lack of IGF-I effects is that total circulating IGF concentrations were not increased by these treatments. IGF-II significantly raised total IGF concentrations at the higher dose only. Plasma IGF-I was reduced by IGF-II infusion, as was plasma IGF-II by IGF-I infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7561636

  2. High-Dose Continuous Oxacillin Infusion Results in Achievement of Pharmacokinetics Targets in Critically Ill Patients with Deep Sternal Wound Infections following Cardiac Surgery

    PubMed Central

    Verdier, Marie-Clémence; Launey, Yoann; Malherbe, Alexandre; Dermu, Marine; Piau, Caroline; Flécher, Erwan; Tribut, Olivier; Mallédant, Yannick; Seguin, Philippe

    2014-01-01

    Knowledge regarding antimicrobial therapy strategies in deep sternal wound infections (DSWI) following cardiac surgery is limited. Therefore, we aimed to determine the steady-state plasma and mediastinal concentrations of oxacillin administered by continuous infusion in critically ill patients with DSWI and to compare these concentrations with the susceptibility of staphylococci recovered. A continuous infusion of oxacillin (150 to 200 mg/kg of body weight/24 h) was administered after a loading dose (50 mg/kg). Plasma and mediastinal concentrations of total and unbound oxacillin were determined 4 h after the loading dose (H4) and then at day 1 (H24) and day 2 (H48). Twelve patients were included. Nine patients exhibited bacteremia, 5 were in septic shock, 8 were positive for Staphylococcus aureus, and 4 were positive for coagulase-negative staphylococci. The median MIC (first to third interquartile range) was 0.25 (0.24 to 0.41) mg/liter. Median plasma concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 64.4 (41.4 to 78.5) and 20.4 (12.4 to 30.4) mg/liter, 56.9 (31.4 to 80.6) and 21.7 (6.5 to 27.3) mg/liter, and 57.5 (32.2 to 85.1) and 20 (14.3 to 35.7) mg/liter. The median mediastinal concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 2.3 (0.7 to 25.9) and 0.9 (<0.5 to 15) mg/liter, 29.1 (19.7 to 38.2) and 12.6 (5.9 to 19.8) mg/liter, and 31.6 (14.9 to 42.9) and 17.1 (6.7 to 26.7) mg/liter. High-dose oxacillin delivered by continuous infusion is a valuable strategy to achieve our pharmacokinetic target (4× MIC) at the site of action at H24. But concerns remain in cases of higher MICs, emphasizing the need for clinicians to obtain the MICs for the bacteria and to monitor oxacillin concentrations, especially the unbound forms, at the target site. PMID:24982092

  3. High-dose continuous oxacillin infusion results in achievement of pharmacokinetics targets in critically ill patients with deep sternal wound infections following cardiac surgery.

    PubMed

    Nesseler, Nicolas; Verdier, Marie-Clémence; Launey, Yoann; Malherbe, Alexandre; Dermu, Marine; Piau, Caroline; Flécher, Erwan; Tribut, Olivier; Mallédant, Yannick; Seguin, Philippe

    2014-09-01

    Knowledge regarding antimicrobial therapy strategies in deep sternal wound infections (DSWI) following cardiac surgery is limited. Therefore, we aimed to determine the steady-state plasma and mediastinal concentrations of oxacillin administered by continuous infusion in critically ill patients with DSWI and to compare these concentrations with the susceptibility of staphylococci recovered. A continuous infusion of oxacillin (150 to 200 mg/kg of body weight/24 h) was administered after a loading dose (50 mg/kg). Plasma and mediastinal concentrations of total and unbound oxacillin were determined 4 h after the loading dose (H4) and then at day 1 (H24) and day 2 (H48). Twelve patients were included. Nine patients exhibited bacteremia, 5 were in septic shock, 8 were positive for Staphylococcus aureus, and 4 were positive for coagulase-negative staphylococci. The median MIC (first to third interquartile range) was 0.25 (0.24 to 0.41) mg/liter. Median plasma concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 64.4 (41.4 to 78.5) and 20.4 (12.4 to 30.4) mg/liter, 56.9 (31.4 to 80.6) and 21.7 (6.5 to 27.3) mg/liter, and 57.5 (32.2 to 85.1) and 20 (14.3 to 35.7) mg/liter. The median mediastinal concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 2.3 (0.7 to 25.9) and 0.9 (<0.5 to 15) mg/liter, 29.1 (19.7 to 38.2) and 12.6 (5.9 to 19.8) mg/liter, and 31.6 (14.9 to 42.9) and 17.1 (6.7 to 26.7) mg/liter. High-dose oxacillin delivered by continuous infusion is a valuable strategy to achieve our pharmacokinetic target (4× MIC) at the site of action at H24. But concerns remain in cases of higher MICs, emphasizing the need for clinicians to obtain the MICs for the bacteria and to monitor oxacillin concentrations, especially the unbound forms, at the target site. PMID:24982092

  4. Continuous administration of an elemental diet induces insulin resistance in neonatal pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously showed that total parenteral nutrition (TPN) compared to intermittent enteral feeding of a milk-based formula induces insulin resistance and hepatic steatosis in neonatal pigs. We hypothesized that intravenous (IV) feeding rather than the nature of the diet (elemental vs polymeric) or ...

  5. Glucose infusion does not suppress increased lipolysis after abdominal surgery.

    PubMed

    Schricker, T; Carli, F; Lattermann, R; Wachter, U; Georgieff, M

    2001-02-01

    The purpose of this study was to investigate the effect of glucose infusion on lipid metabolism after abdominal surgery. Patients (n = 6) with non-metastasized colorectal carcinoma were investigated on the second day after surgery and healthy volunteers were studied after an overnight fast. The rates of glycerol appearance (R(a) glycerol), i.e., lipolysis rates, were assessed by primed continuous infusion of [1,1,2,3,3,-5H2]glycerol before and after 3 h of glucose infusion (4 mg x kg(-1) x min(-1)). Plasma concentrations of glycerol, free fatty acids, glucose, lactate, insulin, and glucagon were determined. Fasting R(a) glycerol was higher in patients than in volunteers (7.7 +/- 1.8 versus 1.9 +/- 0.3 micromol x kg(-1) x min(-1), P < 0.05). Glucose infusion suppressed the R(a) glycerol in volunteers to 1.0 +/- 0.2 micromol x kg(-1) x min(-1) (P < 0.05), whereas lipolysis was not affected in patients. Plasma concentrations of glycerol and free fatty acids similarly decreased during glucose administration by 50% in both groups (P < 0.05). In contrast to the patients, a significant correlation (r = 0.78, P < 0.05) between the R(a) glycerol and plasma glycerol concentration was observed in normal subjects. The hyperglycemic response to glucose infusion was significantly more pronounced (P < 0.05) in patients (10.7 +/- 0.7 mmol/L) than in volunteers (7.1 +/- 0.4 mmol/L), whereas the plasma insulin increased to the same extent in the two groups (P < 0.001). In conclusion, lipolysis rates are increased after abdominal surgery and glucose administration, most likely due to insulin resistance, and fail to inhibit stimulated whole-body lipolysis. PMID:11240333

  6. The Initial Assessment of Daily Insulin Dose in Chinese Newly Diagnosed Type 2 Diabetes

    PubMed Central

    Zhou, Huan; Xu, Hua; Chen, Xie; Teng, Xiangyu; Liu, Qianjing; Liu, Wei

    2016-01-01

    Background. It has been well accepted that insulin therapy is the ideal treatment for newly diagnosed diabetic patients. However, there was no study about assessment of the initial insulin dosage in new onset Chinese patients with type 2 diabetes. Research Design and Methods. 65 newly diagnosed patients with type 2 diabetes (39 males/26 females; HbA1c ≥ 11.80 ± 0.22%) were investigated. All patients had random hyperglycaemia (at 21.8 ± 3.9 mmol/L) on the first day of admission and received insulin infusion intravenously (5 U/per hour). When the blood glucose level dropped to around 10 mmol/L, patients were then transferred to continuous subcutaneous insulin infusion (CSII). The reduction of blood glucose levels in response to per unit of insulin (RBG/RI) was recorded. The target glucose level was achieved in about 3 days. The total daily insulin dose (TDD) and basal insulin dose (TBD) were calculated. Results. TDD was 45.97 ± 1.28 units and TBD was 19.00 ± 0.54 units. TBD was about 40% of the total daily insulin requirement. There was a negative correlation between the ratio of RBG/RI and TDD. Conclusions. TDD was correlated with blood glucose reduction in response to intravenous insulin infusion in Chinese new onset patients with type 2 diabetes. PMID:26697503

  7. Professional continuous glucose monitoring for the identification of type 1 diabetes mellitus among subjects with insulin therapy.

    PubMed

    Chen, Yin-Chun; Huang, Yu-Yao; Li, Hung-Yuan; Liu, Shih-Wei; Hsieh, Sheng-Hwu; Lin, Chia-Hung

    2015-01-01

    The identification of type 1 diabetes in diabetic subjects receiving insulin therapy is sometimes difficult. The purpose of this study is to evaluate whether results of professional continuous glucose monitoring can improve the identification of type 1 diabetes.From 2007 to 2012, 119 adults receiving at least twice-daily insulin therapy and professional continuous glucose monitoring were recruited. Type 1 diabetes was diagnosed by endocrinologists according to American Diabetes Association standards, including a very low C-peptide level (<0.35  pg/mL) or the presence of diabetic ketoacidosis. Continuous glucose monitoring was applied for 3 days.Among 119 subjects, 86 were diagnosed with type 1 diabetes. Subjects with type 1 diabetes were younger (33.8 vs 52.3 years old, P < 0.001), had lower body mass index (BMI, 21.95 vs 24.42, P = 0.003), lower serum creatinine (61.77  vs 84.65 μmol/L, P = 0.001), and higher estimated glomerular filtration rate (108.71 vs 76.48 mg/mL/min/1.73m2, P < 0.001) than subjects with type 2 diabetes. Predictive scores for identification of type 1 diabetes were constructed, including age, BMI, average mean amplitude of glucose excursion in days 2 and 3, and the area under the curve of nocturnal hyperglycemic and hypoglycemic states. The area under the receiver operating characteristic curve was 0.90. With the cutoff of 0.58, the sensitivity was 86.7% and the specificity was 80.8%. The good performance was validated by the leave-one-out method (sensitivity 83.3%, specificity 73.1%).Professional continuous glucose monitoring is a useful tool that improves identification of type 1 diabetes among diabetic patients receiving insulin therapy. PMID:25621692

  8. Acquired von Willebrand disease--hemostatic management of major orthopedic surgery with high-dose immunoglobulin, desmopressin, and continuous factor concentrate infusion.

    PubMed

    Frank, Rolf Dario; Kunz, Dagmar; Wirtz, Dieter Christian

    2002-05-01

    Acquired von Willebrand disease (aVWD) is a rare bleeding disorder that mimics congenital VWD in previously healthy individuals; it is most frequently associated with monoclonal gammopathy. Hemostatic therapy of aVWD is challenging due to the extremely shortened half-life of endogenous and exogenous VWF. High-dose intravenous immunoglobulin (ivIG) is recommended as the treatment of choice, usually rapidly normalizing coagulation; but in case of failure, alternative treatment options are not well explored. We report successful major orthopedic surgery in a 61-year-old woman with multiple myeloma IgG lambda and aVWD. IvIG alone failed to correct hemostasis. However, ivIG pretreatment improved the VWF ristocetin cofactor (VWF:RCo) half-life from only 1.5 hr to more than 4 hr, allowing desmopressin infusions twice daily to maintain sufficient VWF:RCo levels. Because of diminishing desmopressin effect, we attempted for the first time in aVWD a continuous VWF/FVIII infusion (Haemate HS), 2.1-2.7 FVIII U/kg/hr or 51-64 U/kg/day, respectively 4.6-6.0 VWF:RCo U/kg/hr or 110-145 U/kg/day) to reach constant factor levels. The steady-state clearance was 2.4 mL/kg/hr for FVIII:C and 13.5 mL/kg/hr for VWF:RCo. During surgery, VWF:RCo, FVIII:C, and PFA-100 closure time were normalized. Until day 5, VWF:RCo was kept above 50%, from day 6 to 10 at least 30% activity were attained. FVIII:C levels were always >70%. The clinical course was uneventful without bleeding. Two weeks after hip surgery the patient was discharged from the hospital without complaints. The therapy described can be recommended as safe and feasible for further evaluation in aVWD patients who are hyporesponsive to ivIG treatment alone. Continuous VWF/FVIII infusion can improve substitution therapy in aVWD. PMID:11994985

  9. Activity of continuous infusion plus pulse interleukin-2 with famotidine in patients with metastatic kidney cancer or melanoma previously treated with interleukin-2.

    PubMed

    Quan, Walter D Y; Walker, Paul R; Quan, Francine M; Ramirez, Maria; Elsamaloty, Haitham M; Ghai, Vikas; Vinogradov, Mikhail; Liles, Darla K

    2006-10-01

    Lymphokine-activated killer (LAK) cells generated by high-dose continuous infusion interleukin-2 (IL-2) are able to nonspecifically lyse melanoma and kidney cancer cells. In vitro famotidine enhances cytotoxicity of LAK against tumor cells, possibly by increasing IL-2 uptake at the IL-2 receptor on lymphocytes. Outpatient IL-2 regimens typically have response rates of 15% or less, with most patients eventually experiencing progressive disease. Second-line therapy is, therefore, needed. We treated 11 patients (6 with metastatic melanoma; 5 having metastatic kidney cancer) who had previously experienced progressive disease on prior IL-2 regimens, with a combination of famotidine 20 mg intravenously (i.v.) twice per day and continuous-infusion IL-2 18 MIU/M2/24 hours x 72 hours, followed 24 hours later by a pulse IL-2 dose (18 MIU/M2 over 15 minutes). Cycles were repeated every 3 weeks. Patient characteristics were: 9 males, median age 63 years (range, 57-75), median Eastern Cooperative Oncology Group (ECOG) performance status: 1; most common metastatic sites: lungs, lymph nodes, and soft tissue/subcutaneous (s.c.); median number of cycles received: 4; most common toxicities were fever, nausea/emesis, hypophosphatemia, and hypomagnesemia. Five (5) patients (3 with melanoma, 2 with kidney cancer) have had partial responses. Two (2) patients with kidney cancer have been converted to complete responders with resection of residual disease, remaining without relapse at 5+ and 20+ months. Responding sites are lungs, lymph nodes, abdominal mass, and s.c. Median duration of response was 9.5 months. Median survival was 12 months. This combination has activity in patients with metastatic kidney cancer or melanoma who have received prior IL-2. PMID:17105418

  10. Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

    PubMed Central

    Vatner, Daniel F.; Majumdar, Sachin K.; Kumashiro, Naoki; Petersen, Max C.; Rahimi, Yasmeen; Gattu, Arijeet K.; Bears, Mitchell; Camporez, João-Paulo G.; Cline, Gary W.; Jurczak, Michael J.; Samuel, Varman T.; Shulman, Gerald I.

    2015-01-01

    A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance—wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-13C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2′-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action. PMID:25564660

  11. Insulin pump treatment in children and adolescents with type 1 diabetes: experiences of the German working group for insulin pump treatment in pediatric patients.

    PubMed

    Kapellen, Thomas M; Klinkert, Christoph; Heidtmann, Bettina; Jakisch, Bela; Haberland, Holger; Hofer, Sabine E; Holl, Reinhard W

    2010-05-01

    Continuous subcutaneous insulin infusion (CSII) is frequently used in children and adolescents. This review discusses pump treatment, as analyzed by the German Working Group for Insulin Pump Treatment in Pediatric Patients. This group has published several papers, in collaboration with the DPV-Wiss (Diabetes-Patienten-Verlaufsdaten) group. The review includes practical aspects of pump treatment and recent results of CSII in Germany, and compares these with American pump treatment. PMID:20463419

  12. Optimal Dose and Method of Administration of Intravenous Insulin in the Management of Emergency Hyperkalemia: A Systematic Review

    PubMed Central

    Harel, Ziv; Kamel, Kamel S.

    2016-01-01

    given as a continuous intravenous infusion over 60 minutes in patients with severe hyperkalemia (i.e., serum K+ concentration > 6.5 mmol/L) and those with marked EKG changes related to hyperkalemia (e.g., prolonged PR interval, wide QRS complex) as an alternative to 10 units of short acting insulin. Because the risk of hypoglycemia is increased with using large insulin doses, sufficient glucose (60 grams with the administration of 20 units of insulin and 50 grams with the administration of 10 units) should be given to prevent hypoglycemia, and plasma glucose should be frequently monitored. PMID:27148740

  13. A phase I study of prolonged continuous infusion of low dose recombinant interleukin-2 in melanoma and renal cell cancer. Part I: Clinical aspects.

    PubMed Central

    Vlasveld, L. T.; Rankin, E. M.; Hekman, A.; Rodenhuis, S.; Beijnen, J. H.; Hilton, A. M.; Dubbelman, A. C.; Vyth-Dreese, F. A.; Melief, C. J.

    1992-01-01

    The optimal schedule for recombinant interleukin-2 (rIL-2) administration is unclear. Because the clinical and immunological effects of prolonged continuous exposure to rIL-2 are unknown, we have conducted a phase I study to assess the toxicity and feasibility of continuous low dose infusion of rIL-2 (EuroCetus) using central venous access with a portable infusion device on an out-patient basis. Twenty-two patients entered the study, 13 with melanoma and nine with renal cell cancer, age range 26-66 years (median 51), performance status less than or equal to 1. They were treated with one of the following doses per m2 per 24 h: 0.18 x 10(6) IU, 0.6 x 10(6) IU, 1.8 x 10(6) IU, 3 x 10(6) IU, 6 x 10(6) IU and 9 x 10(6) IU. Toxicity was evaluable in 20 patients receiving greater than or equal to 3 weeks treatment duration or in whom treatment was discontinued prematurely because of toxicity. Constitutional symptoms consisting of fatigue, malaise and fever up to 40 degrees C without significant organ dysfunction occurred with doses greater than or equal to 1.8 x 10(6) IU m-2. The maximum tolerated dose was 6 x 10(6) IU m-2 24 h-1. In all patients toxicity reached a peak at 3 weeks and resolved thereafter despite continued rIL-2 treatment. Peripheral blood eosinophilia (up to 66% of white blood cell count) followed the same pattern. An infection of the central venous access occurred in 55% of the patients but this was mostly asymptomatic. Thirteen patients were treated greater than or equal to 6 weeks and were evaluable for tumour response. A partial remission occurred in a patient with melanoma with a dose of 1.8 x 10(6) IU rIL-2 m-2 24 h-1. PMID:1586602

  14. Insulin pumps.

    PubMed

    Pickup, J

    2011-02-01

    The last year has seen a continued uptake of insulin pump therapy in most countries. The USA is still a leader in pump use, with probably some 40% of type 1 diabetic patients on continuous subcutaneous insulin infusion (CSII), but the large variation in usage within Europe remains, with relatively high use (> 15%) in, for example, Norway, Austria, Germany and Sweden and low use (< 5%) in Spain, the UK, Finland and Portugal. There is much speculation on the factors responsible for this variation, and the possibilities include physician attitudes to CSII and knowledge about its benefits and indications for its use (and inappropriate beliefs about dangers), the availability of reimbursement from insurance companies or funding from national health services, the availability of sufficient diabetes nurse educators and dietitians trained in pump procedures, and clear referral pathways for the pump candidate from general practitioner or general hospital to specialist pump centre. There are now several comprehensive national guidelines on CSII use (see ATTD Yearbook 2009) but more work needs to be done in unifying uptake and ensuring all those who can benefit do so. Technology developments recently include increasing use of pumps with continuous glucose monitoring (CGM) connectivity (see elsewhere in this volume) and the emergence of numerous manufacturers developing so-called 'patch pumps', often for the type 2 diabetes market. Interestingly, the evidence base for CSII in this group is not well established, and for this reason the selected papers on CSII in this section include several in this area. The use of CSII in diabetic pregnancy is a long-established practice, in spite of the lack of evidence that it is superior to multiple daily injections (MDI), and few randomised controlled trials have been done in recent years. Several papers in this field this year continue the debate about the usefulness of CSII in diabetic pregnancy and are reviewed here. It is pleasing

  15. The role of insulin glulisine to improve glycemic control in children with diabetes mellitus

    PubMed Central

    Lih, Anna; Hibbert, Emily; Wong, Tang; Girgis, Christian M; Garg, Nidhi; Carter, John N

    2010-01-01

    Glulisine (Apidra®) is a rapid-acting human insulin analog approved for use in children with diabetes mellitus ≥4 years of age. Management of children with type 1 diabetes has seen a shift in favor of mimicking normal physiological insulin responses with multiple daily injections or continuous subcutaneous insulin infusions (CSII). Few studies have compared the rapid-acting insulin analogs in this population but limited data indicate that glulisine is as effective as lispro when used in a basal–bolus regimen. This review appraises the current available studies and reviews on insulin glulisine in children. An extensive keyword search of ‘insulin glulisine’, ‘insulin analogs’, and ‘Apidra’ in the pediatric population was performed. These studies have suggested that glulisine is safe, well tolerated, and is an effective option in the diabetes armamentarium. Further studies are needed to determine its safety for use in CSII pumps in the pediatric population. PMID:21437110

  16. [The subcapsular blastema of the adrenal cortex of the swine after continuous long-term infusion of exogenous ACTH].

    PubMed

    Zintzsch, I; Gutte, G

    1976-01-01

    After long time application of homologous ACTH the morphokinesis of the adrenal cortex of the pig was investigated experimentally. Following results were obtained: 1. In view of the controls the absolute and relative weight of the adrenals is raised considerably. 2. The progressive transformation is followed by the disappearance of the zonal structure of the adrenal cortex, and the parenchyma get the picture of fasciculata cells generally. 3. Nearly exclusive the zona fasciculata consists of great, pale activated spongiocytes with 2 nucleoli frequently. Topochemically glycogen and the lipids are inconstant, however the histochemical activity of succinodehydrogenase, lactate dehydrogenase, acid and alkaline phosphatase are considerable raised in regard of the controls. 4. The zona fasciculata contains degenerated cells isolated only. Signs of extensive regressive changes are not present. 5. The zona glomerulosa is dissolving or eliminating respectively. The consequences for the synthesis of the adrenal steroid hormones are discussed. 6. A large, spongy subcapsular blastema with several cell layers and a rich capillary network develop between the fibrous capsula of the adrenal and the zona fasiculata. The fasciculata cells are the direct continuation of the subcapsular blastema. The blastema contains neither glycogen nor lipids and histochemical activities of the enzymes are absent, too. The significance of the subcapsular blastema for the morphological and functional adaptation of the adrenal cortex in stress are discussed. Under the conditions of the closed hypothalamo-hypophyseal-adrenal control system the new origin of cells (hyperplasia) is not significant for the morphokinetic adaptive reactions of the adrenal cortex. Rather the subcapsular blastema represents a reserve area which after the destruction of the endocrine parenchyma through specific pathogens the organism enabled to the regeneration of the adrenal cortex. PMID:188714

  17. Study protocol for a double blind, randomised, placebo-controlled trial of continuous subpectoral local anaesthetic infusion for pain and shoulder function following mastectomy: SUB-pectoral Local anaesthetic Infusion following MastEctomy (SUBLIME) study

    PubMed Central

    Langford, R; Brown, I; Vickery, J; Mitchell, K; Pritchard, C; Creanor, S

    2014-01-01

    Introduction Over 16 000 mastectomies are performed in England and Wales annually. Acute postoperative pain and nausea are common. The most frequently occurring long-term complications are chronic pain (up to 50%) and reduced shoulder function (reported at 35%). Regional techniques that improve acute postoperative pain relief may reduce the incidence of these complications. This study assesses the effectiveness of a 24-hour continuous local anaesthetic in the subpectoral plane in improving postoperative pain and quality of life in patients undergoing mastectomy. Methods and analysis This is a randomised, double blind, placebo-controlled, two-centre, parallel group trial in women undergoing mastectomy with or without axillary involvement. One hundred and sixty participants will be randomised in a 1:1 ratio to receive either 0.25% levobupivacaine or 0.9% saline by subpectoral infusion postoperatively for 24 h. All participants will be provided with an intravenous morphine patient-controlled analgesia (PCA) system. Participants will be followed-up for 24 h in hospital and at approximately 14 days and 6 months postoperatively. Joint primary outcome measures are total morphine consumption and total pain score (captured via patient-recorded visual analogue scale (VAS) 4 hourly) during the first 24 h postoperatively. Primary statistical analysis of total pain is based on the area under the curve of pain versus time graph. Secondary outcomes include PCA attempts in first 24 h; VAS pain scores and shoulder function by goniometry at 24 h, 14 days (approximately) and 6 months; Verbal Rating Scale pain scores in first 24 h; Brief Pain Inventory and Oxford Shoulder Score at 6 months; duration of hospital stay; incidence of postoperative nausea and vomiting; cost-effectiveness. Ethics and dissemination The study is approved by the South West England Research Ethics Committee (12/SW/0149). Results will be published in a peer-reviewed journal and presented

  18. Exploring drug delivery for the DOT1L inhibitor pinometostat (EPZ-5676): Subcutaneous administration as an alternative to continuous IV infusion, in the pursuit of an epigenetic target.

    PubMed

    Waters, Nigel J; Daigle, Scott R; Rehlaender, Bruce N; Basavapathruni, Aravind; Campbell, Carly T; Jensen, Tyler B; Truitt, Brett F; Olhava, Edward J; Pollock, Roy M; Stickland, Kim A; Dovletoglou, Angelos

    2015-12-28

    Protein methyltransferases are emerging as promising drug targets for therapeutic intervention in human cancers. Pinometostat (EPZ-5676) is a small molecule inhibitor of the DOT1L enzyme, a histone methyltransferase that methylates lysine 79 of histone H3. DOT1L activity is dysregulated in the pathophysiology of rearranged mixed lineage leukemia (MLL-r). Pinometostat is currently in Phase 1 clinical trials in relapsed refractory acute leukemia patients and is administered as a continuous IV infusion (CIV). The studies herein investigated alternatives to CIV administration of pinometostat to improve patient convenience. Various sustained release technologies were considered, and based on the required dose size as well as practical considerations, subcutaneous (SC) bolus administration of a solution formulation was selected for further evaluation in preclinical studies. SC administration offered improved exposure and complete bioavailability of pinometostat relative to CIV and oral administration. These findings warranted further evaluation in rat xenograft models of MLL-r leukemia. SC dosing in xenograft models demonstrated inhibition of MLL-r tumor growth and inhibition of pharmacodynamic markers of DOT1L activity. However, a dosing frequency of thrice daily (t.i.d) was required in these studies to elicit optimal inhibition of DOT1L target genes and tumor growth inhibition. Development of an extended release formulation may prove useful in the further optimization of the SC delivery of pinometostat, moving towards a more convenient dosing paradigm for patients. PMID:26385168

  19. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps

    PubMed Central

    Valla, Vasiliki

    2010-01-01

    Aim. Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Results. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial “closed-loop” systems mimicking the pancreatic activity have been also developed. Conclusions. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients. PMID:20589066

  20. Intraosseous infusion.

    PubMed

    LaRocco, Brian G; Wang, Henry E

    2003-01-01

    Establishing vascular access is vital in the resuscitation of critically-ill children and adults. Intraosseous infusion (IOI) is a viable route for providing vascular access when traditional intravenous methods cannot be accomplished. IOI is relatively easy to perform and is a standard recommended intervention for the resuscitation of both adults and children. The authors review the history, anatomy, technique, and clinical application of IOI. They also highlight the use of IOI in the prehospital setting. PMID:12710793

  1. Insulin glargine: an updated review of its use in the management of diabetes mellitus.

    PubMed

    Dunn, Christopher J; Plosker, Greg L; Keating, Gillian M; McKeage, Kate; Scott, Lesley J

    2003-01-01

    Insulin glargine is a human insulin analogue prepared by recombinant DNA technology. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant in relation to conventional human insulins, with no pronounced peak over 24 hours. This allows once-daily administration as basal therapy. Early randomised trials with insulin glargine generally showed greater reductions in fasting blood or plasma glucose levels and a reduced frequency of nocturnal hypoglycaemia relative to neutral protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus. In addition to this basal therapy, patients continued to use the regular mealtime insulin regimen to which they were accustomed. More recent data with insulin glargine have included evidence of improved glycaemic control, with improvements in satisfaction with treatment over NPH insulin. Furthermore, the time of day at which insulin glargine is injected has no clinically relevant effect on glycaemic control in these patients. There are also data from small, nonblind studies to suggest comparable glycaemic control with insulin glargine and continuous subcutaneous insulin infusion. Results from comparative studies and meta-analyses in individuals with type 2 diabetes show lower incidences of nocturnal hypoglycaemia with insulin glargine than with NPH insulin, with two studies showing a significantly greater improvement in glycosylated haemoglobin levels with insulin glargine than with NPH. Insulin glargine is well tolerated, and is not associated with greater immunogenicity or increases in bodyweight than NPH insulin. Long-term data show maintenance of glycaemic control with insulin glargine

  2. Efficacy of subpleural continuous infusion of local anesthetics after thoracoscopic pulmonary resection for primary lung cancer compared to intravenous patient-controlled analgesia

    PubMed Central

    Jung, Joonho; Haam, Seokjin

    2016-01-01

    Background This study compared the efficacy and side effects of intravenous patient-controlled analgesia (IV-PCA) with those of a subpleural continuous infusion of local anesthetic (ON-Q system) in patients undergoing thoracoscopic pulmonary resection for primary lung cancer. Methods We retrospectively reviewed 66 patients who underwent thoracoscopic pulmonary resection for primary lung cancer from January 2014 to August 2015 (36 in the IV-PCA group and 30 in the ON-Q group). The numeric pain intensity scale (NPIS), additional IV injections for pain control, side effects, and early discontinuation of the pain control device were compared. Results There were no differences in the general characteristics of the two groups. The NPIS scores gradually decreased with time (P<0.001), but the two groups had differences in pattern of NPIS scores (P=0.111). There were no differences in the highest NPIS score during admission (4.75±2.35 vs. 5.27±1.87, P=0.334) or the number of additional IV injections for pain control in the same period (0.72±0.94 for IV-PCA vs. 0.83±0.65 for ON-Q; P=0.575). Side effects such as nausea, dizziness, and drowsiness were significantly more frequent with IV-PCA (36.1% vs. 10.0%, P=0.014), and early discontinuation of the pain control device was more frequent in the IV-PCA group (33.3% vs. 6.7%, P=0.008). Conclusions The ON-Q system was equivalent to the IV-PCA for postoperative pain control after thoracoscopic pulmonary resection for primary lung cancer, and it also had fewer effects and early discontinuations. PMID:27499973

  3. Effects of Continuous Triiodothyronine Infusion on Citric Acid Cycle in the Normal Immature Swine Heart under Extracorporeal Membrane Oxygenation in vivo

    SciTech Connect

    Kajimoto, Masaki; O'Kelly-Priddy, Colleen M.; Ledee, Dolena R.; Xu, Chun; Isern, Nancy G.; Olson, Aaron; Portman, Michael A.

    2014-02-13

    Extracorporeal membrane oxygenation (ECMO) is frequently used in infants with postoperative cardiopulmonary failure. ECMO also suppresses circulating triiodothyronine (T3) levels and modifies myocardial metabolism. We assessed the hypothesis that T3 supplementation reverses ECMO induced metabolic abnormalities in the immature heart. Twenty-two male Yorkshire pigs (age 25-38 days) with ECMO were received [2-13C]lactate, [2,4,6,8-13C]octanoate (medium chain fatty acid) and [U-13C]long-chain fatty acids as metabolic tracers either systemically (totally physiological intracoronary concentration) or directly into the coronary artery (high substrate concentration) for the last 60 minutes of each protocol. Nuclear magnetic resonance (NMR) analysis of left ventricular tissue determined the fractional contribution (Fc) of these substrates to the citric acid cycle (CAC). Fifty percent of the pigs in each group received intravenous T3 supplement (bolus at 0.6 μg/kg and then continuous infusion at 0.2 μg/kg/hour) during ECMO. Under both substrate loading conditions T3 significantly increased lactate-Fc with a marginal increase in octanoate-Fc. Both T3 and high substrate provision increased myocardial energy status indexed by [Phosphocreatine]/[ATP]. In conclusion, T3 supplementation promoted lactate metabolism to the CAC during ECMO suggesting that T3 releases inhibition of pyruvate dehydrogenase. Manipulation of substrate utilization by T3 may be used therapeutically during ECMO to improve resting energy state and facilitate weaning.

  4. Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological) delivery

    PubMed Central

    Matteucci, Elena; Giampietro, Ottavio; Covolan, Vera; Giustarini, Daniela; Fanti, Paolo; Rossi, Ranieri

    2015-01-01

    Insulin is a life-saving medication for people with type 1 diabetes, but traditional insulin replacement therapy is based on multiple daily subcutaneous injections or continuous subcutaneous pump-regulated infusion. Nonphysiologic delivery of subcutaneous insulin implies a rapid and sustained increase in systemic insulin levels due to the loss of concentration gradient between portal and systemic circulations. In fact, the liver degrades about half of the endogenous insulin secreted by the pancreas into the venous portal system. The reverse insulin distribution has short- and long-term effects on glucose metabolism. Thus, researchers have explored less-invasive administration routes based on innovative pharmaceutical formulations, which preserve hormone stability and ensure the therapeutic effectiveness. This review examines some of the recent proposals from clinical and material chemistry point of view, giving particular attention to patients’ (and diabetologists’) ideal requirements that organic chemistry could meet. PMID:26124635

  5. Postoperative pain control using continuous i.m. bupivacaine infusion plus patient-controlled analgesia compared with epidural analgesia after major hepatectomy

    PubMed Central

    Wong-Lun-Hing, Edgar M; van Dam, Ronald M; Welsh, Fenella K S; Wells, John K G; John, Timothy G; Cresswell, Adrian B; Dejong, Cornelis H C; Rees, Myrddin

    2014-01-01

    Objectives There is debate concerning the best mode of delivery of analgesia following liver resection, with continuous i.m. infusion of bupivacaine (CIB) plus patient-controlled i.v. analgesia (PCA) suggested as an alternative to continuous epidural analgesia (CEA). This study compares these two modalities. Methods A total of 498 patients undergoing major hepatectomy between July 2004 and July 2011 were included. Group 1 received CIB + PCA (n = 429) and Group 2 received CEA (n = 69). Groups were analysed on baseline patient and surgical characteristics. Primary endpoints were pain severity scores and total opioid consumption. Secondary endpoints were pain management failures, need for rescue medication, postoperative (opioid-related) morbidity and hospital length of stay (LoS). Results In both groups pain was well controlled and >70% of patients had no or minimal pain on PoDs 1 and 2. The numbers of patients experiencing severe pain were similar in both groups: PoD 1 at rest: 0.3% in Group 1 and 0% in Group 2 (P = 1.000); PoD 1 on movement: 8% in Group 1 and 2% in Group 2 (P = 0.338); PoD 2 at rest: 0% in Group 1 and 2% in Group 2 (P = 0.126), and PoD 2 on movement: 5% in Group 1 and 5% in Group 2 (P = 1.000). Although the CIB + PCA group required more opioid rescue medication on PoD 0 (53% versus 22%; P < 0.001), they used less opioids on PoDs 0–3 (P ≤ 0.001), had lower morbidity (26% versus 39%; P = 0.018), and a shorter LoS (7 days versus 8 days; P = 0.005). Conclusions The combination of CIB + PCA provides pain control similar to that provided by CEA, but facilitates lower opioid consumption after major hepatectomy. It has the potential to replace epidural analgesia, thereby avoiding the occurrence of rare but serious complications. PMID:24151899

  6. Improved ischemic island skin flap survival with continuous intraarterial infusion of adenosine triphosphate--magnesium chloride and superoxide dismutase: a rat model.

    PubMed

    Zimmerman, T J; Sasaki, G H; Khattab, S

    1987-03-01

    Neurovascular island skin flaps are still hampered by occasional necrosis of their most distal aspect. Cells subjected to prolonged hypoxic conditions become intracellularly depleted of needed metabolic substrates and eventually die. Once hypoxic conditions are improved, ischemic tissue suffers further injury from the rapid accumulation of oxygen free radicals. This study showed 53% survival of a standard random flap constructed on the inferior epigastric neurovascular bundle of a rat. Random flap survival increased to 65% after intraarterial infusion of adenosine triphosphate--magnesium chloride (ATP-MgCl2); to 75% after superoxide dismutase infusion; and to 98% after combined ATP-MgCl2 and superoxide dismutase infusion. Neither substrate appeared to act by increasing blood flow to the ischemic tissue. PMID:3296921

  7. Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month ‘proof-of-concept’ study

    PubMed Central

    Owens, D R; Luzio, S D; Sert-Langeron, C; Riddle, M C

    2011-01-01

    Aim Stepwise intensification of insulin treatment to match the progressive decline of endogenous insulin secretion has been shown to be an effective management strategy in type 2 diabetes mellitus (T2DM). The efficacy of initiating and titrating a single bolus dose of insulin glulisine to baseline insulin glargine plus oral hypoglycaemic agents (OHAs) was investigated. Methods This was a 6-month, parallel-group, randomized, open-label, Phase IV study conducted in the US, UK and Russia. People with T2DM (HbA1c 7.5–9.5%) using any basal insulin underwent a 3-month run-in period on insulin glargine titrated to optimize fasting blood glucose (BG) control. Those with HbA1c >7.0% were randomized to either continue prior therapy (n = 57) or to add a single dose of insulin glulisine (n = 49) immediately prior to the main meal for a further 3 months. Two different titration algorithms were employed for the bolus dose, targeting 2-h postprandial BG ≤135 mg/dL (≤7.5 mmol/l; Russia and UK) or pre-meal/bedtime BG 100–120 mg/dl (5.5–6.7 mmol/l; US). Results HbA1c and fasting plasma glucose levels decreased during the run-in period. In the 3 months after randomization, more participants in the basal-plus-bolus group reached HbA1c <7.0% than the basal-only control group (22.4 vs. 8.8%; p < 0.05), with significantly greater reduction of HbA1c (−0.37 vs. −0.11%; p = 0.0290). Rates of hypoglycaemia and mean weight change were comparable between the treatment groups. Conclusions In people with T2DM inadequately controlled on basal insulin plus OHAs, adding a single injection of insulin glulisine prior to the main meal significantly improves glucose control without undesired side effects. PMID:21679291

  8. [Cases of advanced cholangiocarcinoma showing partial response by the combination chemotherapy including protracted continuous infusion of 5-FU combined with intravenous administration of low-dose leucovorin and intra-arterial administration of MMC and CQ].

    PubMed

    Tsushima, K; Sakata, Y; Shiratori, Y; Sakamoto, J; Koeda, J; Yamada, Y; Soma, N; Tamura, K; Yoshiwara, A; Soma, Y

    1991-12-01

    We treated a patient with advanced cholangiocarcinoma with a new combination chemotherapy (modified MQF). The regimen consisted of intra-arterial administration of MMC (20 mg/body) and CQ (4 mg/body), protracted continuous infusion of 5-FU (500 mg/body) and intravenous administration of low-dose leucovorin (30 mg/body). More than 50% reduction in the liver tumor for over 4 weeks was obtained by the therapy. As for toxicity, diarrhea and stomatitis were observed. PMID:1660702

  9. Medanta insulin protocols in patients undergoing cardiac surgery

    PubMed Central

    Bansal, Beena; Mithal, Ambrish; Carvalho, Pravin; Mehta, Yatin; Trehan, Naresh

    2014-01-01

    Hyperglycemia is common in patients undergoing cardiac surgery and is associated with poor outcomes. This is a review of the perioperative insulin protocol being used at Medanta, the Medicity, which has a large volume cardiac surgery setup. Preoperatively, patients are usually continued on their preoperative outpatient medications. Intravenous insulin infusion is intiated postoperatively and titrated using a column method with a choice of 7 scales. Insulin dose is calculated as a factor of blood glucose and patient's estimated insulin sensitivity. A comparison of this protocol is presented with other commonly used protocols. Since arterial blood gas analysis is done every 4 hours for first two days after cardiac surgery, automatic data collection from blood gas analyzer to a central database enables collection of glucose data and generating glucometrics. Data auditing has helped in improving performance through protocol modification. PMID:25143899

  10. Technosphere insulin: an inhaled prandial insulin product.

    PubMed

    Neumiller, Joshua J; Campbell, R Keith

    2010-06-01

    Given the important role of insulin in the treatment of diabetes mellitus and in light of common barriers to insulin use, new strategies for insulin delivery by routes other than intravenous and subcutaneous injection have been investigated since the discovery of insulin in the 1920s. Most companies researching and developing pulmonary administration systems for the use of insulin announced the termination of product development following the failure of the first US FDA-approved inhaled insulin product, Exubera. One company in particular continued their pursuit of a useful inhaled insulin product. MannKind Corporation has developed a powder formulation of insulin that allows for a high percentage of the administered insulin to be absorbed via the lung. Their product, AFREZZA (Technosphere insulin), is currently under review by the FDA for use in patients with diabetes. Technosphere insulin appears to overcome some of the barriers that contributed to the market withdrawal of Exubera by the manufacturer. Studies with Technosphere insulin have shown it to be a unique insulin formulation in that it is very rapid acting, has a relatively short duration of action, and is efficacious in terms of improved glycemic control without contributing to increased weight gain or the incidence of hypoglycemia when compared with other prandial insulin products. Additionally, Technosphere insulin has demonstrated a favorable safety and tolerability profile in clinical studies to date. PMID:20462282

  11. Effect of continuous infusion of a GnRH agonist (Buserelin) on ovarian hormone secretion and estrous cycle length in cows.

    PubMed

    Mann, G E; Lamming, G E

    2000-07-15

    The importance of the ovarian steroid hormones estradiol and progesterone in the control of luteolysis in domestic ruminants is well established. However, there is a lack of studies specifically investigating the effect of stimulating "physiological" changes in endogenous estradiol or progesterone secretion on subsequent luteolysis. In this study we have stimulated endogenous ovarian hormone secretion by infusion of the GnRH analogue, Buserelin, and have assessed the effect of these changes on the timing of luteolysis. Concentrations of estradiol and progesterone were monitored in plasma samples collected from 6 mature, cyclic, lactating, Friesian cows during a control cycle and during a cycle in which Buserelin was infused via osmotic minipump (8.6 microg/h) for 28 days starting on Day 2 of the cycle. Buserelin infusion had little effect on progesterone secretion but did result in a marked stimulation of estradiol secretion from Days 6 to 10 of the cycle (treated cycle 4.3+/-0.2 pg/mL; control cycle 1.8+/-0.3 pg/mL; P<0.001). In addition, there was a significant advancement in the timing of luteolysis during the Buserelin -infused cycle (Day 19.3+/-0.3 compared with Day 21.3+/-0.4; P<0.01). In this study, we have found that infusion of buserelin caused both a significant stimulation of estradiol secretion from the first follicle and a significant advancement in the timing of luteolysis. We hypothesise that the increased secretion of estradiol may have been involved in causing this advancement of luteolysis. PMID:11003303

  12. Glucose tolerance, blood lipid, insulin and glucagon concentration after single or continuous administration of aspartame in diabetics.

    PubMed

    Okuno, G; Kawakami, F; Tako, H; Kashihara, T; Shibamoto, S; Yamazaki, T; Yamamoto, K; Saeki, M

    1986-04-01

    A nutritive sweetener, aspartame (L-aspartyl-L-phenylalanine methylester) was administered orally to normal controls and diabetic patients in order to evaluate effects on blood glucose, lipids and pancreatic hormone secretion. An oral glucose tolerance test was also performed in the same subjects as a control study of aspartame administration. In 7 normal controls and 22 untreated diabetics, a single dose of 500 mg aspartame, equivalent to 100 g glucose in sweetness, induced no increase in blood glucose concentration. Rather, a small but significant decrease in blood glucose was noticed 2 or 3 h after administration. The decrease in blood glucose was found to be smallest in the control and became greater as the diabetes increased in severity. No significant change in blood insulin or glucagon concentration during a 3-h period was observed in either the controls or the diabetics. The second study was designed to determine the effects of 2 weeks' continuous administration of 125 mg aspartame, equal in sweetness to the mean daily consumption of sugar (20-30 g) in Japan, to 9 hospitalized diabetics with steady-state glycemic control. The glucose tolerance showed no significant change after 2 weeks' administration. Fasting, 1 h and 2 h postprandial blood glucose, blood cholesterol, triglyceride and HDL-cholesterol were also unaffected. From these and other published results, aspartame would seem to be a useful alternative nutrient sweetener for patients with diabetes mellitus. PMID:3522147

  13. Insulin Aspart in the Management of Diabetes Mellitus: 15 Years of Clinical Experience.

    PubMed

    Hermansen, Kjeld; Bohl, Mette; Schioldan, Anne Grethe

    2016-01-01

    Limiting excessive postprandial glucose excursions is an important component of good overall glycemic control in diabetes mellitus. Pharmacokinetic studies have shown that insulin aspart, which is structurally identical to regular human insulin except for the replacement of a single proline amino acid with an aspartic acid residue, has a more physiologic time-action profile (i.e., reaches a higher peak and reaches that peak sooner) than regular human insulin. As expected with this improved pharmacokinetic profile, insulin aspart demonstrates a greater glucose-lowering effect compared with regular human insulin. Numerous randomized controlled trials and a meta-analysis have also demonstrated improved postprandial control with insulin aspart compared with regular human insulin in patients with type 1 or type 2 diabetes, as well as efficacy and safety in children, pregnant patients, hospitalized patients, and patients using continuous subcutaneous insulin infusion. Studies have demonstrated that step-wise addition of insulin aspart is a viable intensification option for patients with type 2 diabetes failing on basal insulin. Insulin aspart has shown a good safety profile, with no evidence of increased receptor binding, mitogenicity, stimulation of anti-insulin antibodies, or hypoglycemia compared with regular human insulin. In one meta-analysis, there was evidence of a lower rate of nocturnal hypoglycemia compared with regular human insulin and, in a trial that specifically included patients with a history of recurrent hypoglycemia, a significantly lower rate of severe hypoglycemic episodes. The next generation of insulin aspart (faster-acting insulin aspart) is being developed with a view to further improving on these pharmacokinetic/pharmacodynamic properties. PMID:26607485

  14. Spotlight on insulin glargine in type 1 and 2 diabetes mellitus.

    PubMed

    McKeage, Kate; Goa, Karen L

    2002-01-01

    Insulin glargine is a recombinant human insulin analog produced by DNA technology using a nonpathogenic strain of Escherichia coli. Two modifications of human insulin result in a stable molecule which is soluble in slightly acidic conditions (pH 4.0) and precipitates in the neutral pH of subcutaneous tissue. Because of these properties, absorption of insulin glargine is delayed and the analog provides a fairly constant, basal insulin supply without peaks in plasma insulin levels for approximately 24 hours, similar to that achieved by a continuous subcutaneous insulin infusion. Insulin glargine is indicated as a once daily subcutaneous injection to provide basal glycemic control in adults and children aged >6 years with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Fasting plasma glucose and fasting blood glucose levels generally improved to a greater extent in patients with type 1 diabetes mellitus receiving insulin glargine than patients who administered Neutral Protamine Hagedorn (NPH) insulin. In patients with type 1 or 2 disease, glycosylated hemoglobin levels were slightly reduced and to a similar extent with insulin glargine and NPH insulin. Most clinical trials in patients with type 1 or 2 diabetes mellitus demonstrated a lower incidence of hypoglycemia, especially nocturnal hypoglycemia, with insulin glargine compared with NPH insulin. One of the most common adverse events with insulin glargine treatment was injection site pain which, in some studies, occurred more frequently than in patients receiving NPH insulin. In all cases the symptoms were mild and treatment discontinuation was not required. Otherwise, the drug is well tolerated and does not appear to be immunogenic. In conclusion, insulin glargine once a day provides basal control of glycemia for approximately 24 hours without inducing peaks in plasma insulin levels in patients with type 1 or 2 diabetes mellitus. In long-term, well designed trials insulin glargine once daily

  15. Resource guide 2004. Insulin delivery.

    PubMed

    2004-01-01

    Syringes...pumps...jet infectors...pens...infusers...they all do the same basic thing--deliver insulin. These items carry insulin through the outermost layer of skin and into fatty tissue so it can be used by the body. This section will also cover injection aids, products designed to make infecting easier. PMID:14976945

  16. Insulin therapy in type 2 diabetes.

    PubMed

    Mudaliar, S; Edelman, S V

    2001-12-01

    concentration is normalized. If combination therapy is not successful, a split-mixed regimen of intermediate- and rapid-acting insulin equally divided between the prebreakfast and pre-dinner periods is advised for oese patients, and more intensive regimens are advised for thin patients. Insulin therapy is invariably associated with weight gain and hypoglycemia. The use of metformin or glitazones in combination with insulin has been demonstrated to have insulin-sparing properties. Also, metformin use may ameliorate weight gain. The use of continuous subcutaneous insulin infusion pumps can be particularly beneficial in treating patients with type 2 diabetes mellitus who do not respond satisfactorily to more conventional treatment strategies. Intraperitoneal insulin delivery systems hold considerable promise in type 2 diabetes because of their more physiologic delivery of insulin and their ability to inhibit hepatic glucose production selectively, with less peripheral insulinemia than with subcutaneous insulin injections. Newer insulin analogues such as the rapidly acting Lispro insulin and the peakless, long-acting glargine insulin are increasingly being used because of their unique physiologic pharmacokinetics. New developments such as inhaled and buccal insulin preparations will also make it easier for many patients to initiate and maintain a proper insulin regimen. Finally, a new generation of gut peptides such as amylin and GLP-1 will add a new dimension to glycemic control through modification of nutrient delivery and other mechanisms; however, the ultimate goal in the management of type 2 diabetes is the primary prevention of the disease. The Diabetes Prevention Program (DPP) sponsored by the National Institutes of Health has currently randomly assigned more than 3000 persons with impaired glucose tolerance and at high risk of developing diabetes into three treatment arms: metformin arm, an intensive lifestyle-modification arm, and a placebo arm. The study will conclude in

  17. Use of Insulin Pumps in India: Suggested Guidelines Based on Experience and Cultural Differences

    PubMed Central

    Das, Ashok Kumar; Unnikrishnan, Ranjit; Joshi, Shashank R.; Ramachandran, Ambady; Shamsudeen, Jisha; Krishnan, Gopika; Jothydev, Sunitha; Mohan, Viswanathan

    2010-01-01

    Abstract All type 1 diabetes mellitus (T1DM) subjects and the majority of type 2 diabetes mellitus (T2DM) subjects at one time or another require insulin to sustain life. Syringes and pens are presently the most popular insulin delivery devices. Though in use for more than 3 decades, insulin pumps are now being more commonly used because of their unique ability to continuously infuse insulin, closely mimicking that of physiological secretion from a normal pancreas. Unlike insulin shots with syringes, pump infusion sites need to be changed less frequently. Scientific evidence from published studies have proven added benefit of insulin pumps in improving quality of life, normalizing sugars in recalcitrant diabetes, improving sexual function, and relieving the intractable pain of neuropathy. In the western world, pumps are commonly used with T1DM subjects, whereas in India 80% of pumpers are T2DM subjects. The success of insulin pump therapy depends on selection of the right candidate, extensive education, motivation, and implementing the sophisticated programs with skill. However, all affordable patients are not ideal candidates for pump therapy because for successful continuation of pump therapy other inclusion criteria should also be fulfilled. Among the other indications discussed are a high level of insulin resistance, brittle diabetes, chronic kidney disease on renal replacement therapy, and continuous glucose monitoring pattern strongly suggesting need for a variable basal insulin infusion rate. In International Diabetes Foundation data released in 2009, estimated diabetes prevalence for 2010 is 285 million, representing 6.4% of the world's adult population, with a prediction that by 2030 the number of people with diabetes will have increased to 438 million. Considering this massive growth in T2DM and its propensity after 10–15 years to lead to an insulin-deficient state, available evidence from studies is a compelling indication not to deny the benefits of

  18. Use of insulin pumps in India: suggested guidelines based on experience and cultural differences.

    PubMed

    Kesavadev, Jothydev; Das, Ashok Kumar; Unnikrishnan, Ranjit; Joshi, Shashank R; Ramachandran, Ambady; Shamsudeen, Jisha; Krishnan, Gopika; Jothydev, Sunitha; Mohan, Viswanathan

    2010-10-01

    All type 1 diabetes mellitus (T1DM) subjects and the majority of type 2 diabetes mellitus (T2DM) subjects at one time or another require insulin to sustain life. Syringes and pens are presently the most popular insulin delivery devices. Though in use for more than 3 decades, insulin pumps are now being more commonly used because of their unique ability to continuously infuse insulin, closely mimicking that of physiological secretion from a normal pancreas. Unlike insulin shots with syringes, pump infusion sites need to be changed less frequently. Scientific evidence from published studies have proven added benefit of insulin pumps in improving quality of life, normalizing sugars in recalcitrant diabetes, improving sexual function, and relieving the intractable pain of neuropathy. In the western world, pumps are commonly used with T1DM subjects, whereas in India 80% of pumpers are T2DM subjects. The success of insulin pump therapy depends on selection of the right candidate, extensive education, motivation, and implementing the sophisticated programs with skill. However, all affordable patients are not ideal candidates for pump therapy because for successful continuation of pump therapy other inclusion criteria should also be fulfilled. Among the other indications discussed are a high level of insulin resistance, brittle diabetes, chronic kidney disease on renal replacement therapy, and continuous glucose monitoring pattern strongly suggesting need for a variable basal insulin infusion rate. In International Diabetes Foundation data released in 2009, estimated diabetes prevalence for 2010 is 285 million, representing 6.4% of the world's adult population, with a prediction that by 2030 the number of people with diabetes will have increased to 438 million. Considering this massive growth in T2DM and its propensity after 10–15 years to lead to an insulin-deficient state, available evidence from studies is a compelling indication not to deny the benefits of continuous

  19. Development of insulin delivery systems.

    PubMed

    Siddiqui, N I; Siddiqui, Ni; Rahman, S; Nessa, A

    2008-01-01

    Delivery system of insulin is vital for its acceptance and adherence to therapy for achieving the glycemic targets. Enormous developments have occurred in the delivery system of insulin during the last twenty years and each improvement was aimed at two common goals: patients convenience and better glycemic control. Till to date, the various insulin delivery systems are: syringes/vials, injection aids, jet injectors, transmucosal delivery, transdermal delivery, external insulin infusion pump, implantable insulin pumps, insulin pens and insulin inhalers. Syringe/vial is the oldest and conventional method, still widely used and relatively cheaper. Modern plastic syringes are disposable, light weight with microfine needle for patients convenience and comfort. Oral route could be the most acceptable and viable, if the barriers can be overcome and under extensive trial. Insulin pen device is an important milestone in the delivery system of insulin as it is convenient, discrete, painless, attractive, portable with flexible life style and improved quality of life. More than 80% of European diabetic patients are using insulin pen. Future digital pen will have better memory option, blood glucose monitoring system, insulin dose calculator etc. Insulin infusion pump is a good option for the children, busy patients with flexible lifestyle and those who want to avoid multiple daily injections. Pulmonary route of insulin delivery is a promising, effective, non-invasive and acceptable alternative method. Exubera, the world first insulin inhaler was approved by FDA in 28 January 2006. But due to certain limitations, it has been withdrawn from the market in October 2007. The main concern of inhaled insulin are: long term pulmonary safety issues, cost effectiveness and user friendly device. In future, more acceptable and cost effective insulin inhaler will be introduced. Newer avenues are under extensive trial for better future insulin delivery systems. PMID:18285745

  20. Linearity of β-cell response across the metabolic spectrum and to pharmacology: insights from a graded glucose infusion-based investigation series.

    PubMed

    Shankar, Sudha S; Shankar, R Ravi; Mixson, Lori A; Miller, Deborah L; Chung, Christopher; Cilissen, Caroline; Beals, Chan R; Stoch, S Aubrey; Steinberg, Helmut O; Kelley, David E

    2016-06-01

    The graded glucose infusion (GGI) examines insulin secretory response patterns to continuously escalating glycemia. The current study series sought to more fully appraise its performance characteristics. Key questions addressed were comparison of the GGI to the hyperglycemic clamp (HGC), comparison of insulin secretory response patterns across three volunteer populations known to differ in β-cell function (healthy nonobese, obese nondiabetic, and type 2 diabetic), and characterization of effects of known insulin secretagogues in the context of a GGI. Insulin secretory response was measured as changes in insulin, C-peptide, insulin secretion rates (ISR), and ratio of ISR to prevailing glucose (ISR/G). The GGI correlated well with the HGC (r = 0.72 for ISR/G, P < 0.01). The insulin secretory response in type 2 diabetes (T2DM) was significantly blunted (P < 0.001), whereas it was significantly increased in obese nondiabetics compared with healthy nonobese (P < 0.001). Finally, robust (P < 0.001 over placebo) pharmacological effects were observed in T2DM and healthy nonobese volunteers. Collectively, the findings of this investigational series bolster confidence that the GGI has solid attributes for assessing insulin secretory response to glucose across populations and pharmacology. Notably, the coupling of insulin secretory response to glycemic changes was distinctly and uniformly linear across populations and in the context of insulin secretagogues. (Clinical Trial Registration Nos. NCT00782418, NCT01055340, NCT01373450). PMID:27072496

  1. Blood Glucose Control Using a Novel Continuous Blood Glucose Monitor and Repetitive Intravenous Insulin Boluses: Exploiting Natural Insulin Pulsatility as a Principle for a Future Artificial Pancreas

    PubMed Central

    Skjaervold, Nils K.; Östling, Dan; Hjelme, Dag R.; Spigset, Olav; Lyng, Oddveig

    2013-01-01

    The aim of this study was to construct a glucose regulatory algorithm by employing the natural pulsatile pattern of insulin secretion and the oscillatory pattern of resting blood glucose levels and further to regulate the blood glucose level in diabetic pigs by this method. We developed a control algorithm based on repetitive intravenous bolus injections of insulin and combined this with an intravascular blood glucose monitor. Four anesthetized pigs were used in the study. The animals developed a mildly diabetic state from streptozotocin pretreatment. They were steadily brought within the blood glucose target range of 4.5–6.0 mmol/L in 21 to 121 min and kept within that range for 128 to 238 min (hypoglycemic values varied from 2.9 to 51.1 min). The study confirmed our hypotheses regarding the feasibility of this new principle for blood glucose control, and the algorithm was constantly improved during the study to produce the best results in the last animals. The main obstacles were the drift of the IvS-1 sensor and problems with the calibration procedure, which calls for an improvement in the sensor stability before this method can be applied fully in new studies in animals and humans. PMID:24369461

  2. Continuation or discontinuation of pioglitazone when starting bedtime insulin in patients with poorly controlled type 2 diabetes in an inner-city population

    PubMed Central

    Mojtahedzadeh, Mona; Lee, Martin L.; Friedman, Theodore C.

    2016-01-01

    Objective We studied the impact of continuing versus discontinuing pioglitazone on hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and weight when starting bedtime insulin in patients with poor glycemic control. Methods We retrospectively analyzed data from a 13-month randomized control trial on 77 patients with type 2 diabetes mellitus (DM), who despite maximum doses of three oral diabetes medications (metformin, sulfonylurea and pioglitazone) had HbA1C levels above 7.5%. Patients were randomized to either continuing or discontinuing pioglitazone in addition to starting and up-titrating bedtime insulin. HbA1C, FPG, and weight were assessed at baseline, 3 months, 7 months and 13 months with the differences from baseline for the two groups compared at each of the three time points using the Wilcoxon rank sum test. Results We found that HbA1c was significantly lower at the 7-month (p=0.01) and 13-month time points (p=0.036) and FPG was significantly lower at all three time points in the group continuing pioglitazone compared with those discontinuing pioglitazone. Continuing pioglitazone resulted in a greater increase in weight at the 3-month (p=0.002), 7-month (P=0.0001) and 13-month (P=0.00003) time points. Patients with the lowest HbA1c (< 8.2%) at baseline were more likely to benefit from continuing pioglitazone than those with higher baseline HbA1c. Patients who started insulin and discontinued pioglitazone had similar HbA1c, FPG and weight at the three time points as at baseline, suggesting that pioglitazone and bedtime insulin has similar glycemic effect in this population. Conclusions We conclude that in patients with uncontrolled type 2 DM, continuing pioglitazone while concurrently starting bedtime insulin within a 13-month period led to a significant decrease in both HbA1c and FPG levels compared with those who did not receive pioglitazone; however weight increased during this period. PMID:26215435

  3. The efficacy of the time-scheduled decremental continuous infusion of fentanyl for postoperative patient-controlled analgesia after total intravenous anesthesia

    PubMed Central

    Kim, Jong-Yeop; Park, Sung-Yong; Chang, Hyuk Soo; Nam, Si-Kwon

    2013-01-01

    Background Intravenous fentanyl has been used for acute postoperative pain management, but has not always provided reliable adequate analgesia, including patient-controlled analgesia (PCA). The purpose of this study was to investigate the efficacy of time-scheduled decremental infusion of fentanyl for postoperative analgesia. Methods Ninety-nine patients, aged 20-65 years, undergoing laparoscopic-assisted hysterectomy using total intravenous anesthesia (TIVA) were randomly assigned into one of the three groups. Their background infusions of fentanyl diluent (2 ml/hr of diluent was equivalent with 0.5 µg/kg/hr of fentanyl) with PCA were maintained at the fixed-rate of 2 ml/hr until the postoperative 24 hr (FX2-2-2), or at the decremental rates of 6.0, 4.0, 2.0 ml/hr (D6-4-2) and 8.0, 4.0, 2.0 ml/hr (D8-4-2). The visual analogue score (VAS), incidence of inadequate analgesia, frequency of PCA intervention, and side effects were evaluated. Results VAS was significantly higher in FX2-2-2 than in D6-4-2 and D8-4-2 until postoperative 3 hr (P < 0.05). After postoperative 4 hr, VAS was significantly higher in FX2-2-2 than D8-4-2 (P < 0.05). The incidence of inadequate analgesia of FX2-2-2 was significantly greater than D6-4-2 (P = 0.038) and D8-4-2 (P < 0.001) until postoperative 1 hr. None of the patients had ventilatory depression, and postoperative nausea and vomiting were not significant among the groups. Conclusions The time-scheduled decremental background infusion regimens of fentanyl, based on the pharmacokinetic model, could provide more effective postoperative pain management after TIVA, and the side effects and the risk for morbidity were not different from the fixed-rate infusion regimen. PMID:24427461

  4. Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans.

    PubMed Central

    De Feo, P; Gaisano, M G; Haymond, M W

    1991-01-01

    Insulin deficiency decreases tissue protein synthesis, albumin mRNA concentration, and albumin synthesis in rats. In contrast, insulin deficiency does not change, or, paradoxically, increases estimates of whole body protein synthesis in humans. To determine if such estimates of whole body protein synthesis could obscure potential differential effects of insulin on the synthetic rates of individual proteins, we determined whole body protein synthesis and albumin and fibrinogen fractional synthetic rates using 5-h simultaneous infusions of [14C]leucine and [13C]bicarbonate, in six type 1 diabetics during a continuous i.v. insulin infusion (to maintain euglycemia) and after short-term insulin withdrawal (12 +/- 2 h). Insulin withdrawal increased (P less than 0.03) whole body proteolysis by approximately 35% and leucine oxidation by approximately 100%, but did not change 13CO2 recovery from NaH13CO3 or estimates of whole body protein synthesis (P = 0.21). Insulin deficiency was associated with a 29% decrease (P less than 0.03) in the albumin fractional synthetic rate but a 50% increase (P less than 0.03) in that of fibrinogen. These data provide strong evidence that albumin synthesis in humans is an insulin-sensitive process, a conclusion consistent with observations in rats. The increase in fibrinogen synthesis during insulin deficiency most likely reflects an acute phase protein response due to metabolic stress. These data suggest that the absence of changes in whole body protein synthesis after insulin withdrawal is the result of the summation of differential effects of insulin deficiency on the synthesis of specific body proteins. PMID:1909352

  5. Influence of Continuous Physiologic Hyperinsulinemia on Glucose Kinetics and Counterregulatory Hormones in Normal and Diabetic Humans

    PubMed Central

    Saccà, Luigi; Sherwin, Robert; Hendler, Rosa; Felig, Philip

    1979-01-01

    The effects of continuous infusions of insulin in physiologic doses on glucose kinetics and circulating counterregulatory hormones (epinephrine, norepinephrine, glucagon, cortisol, and growth hormone) were determined in normal subjects and diabetics. The normals received insulin at two dose levels (0.4 and 0.25 mU/kg per min) and the diabetics received the higher dose (0.4 mU/kg per min) only. In all three groups of studies, continuous infusion of insulin resulted in an initial decline in plasma glucose followed by stabilization after 60-180 min. In the normal subjects, with the higher insulin dose there was a fivefold rise in plasma insulin. Plasma glucose fell at a rate of 0.73±0.12 mg/min for 45 min and then stabilized at 55±3 mg/dl after 60 min. The initial decline in plasma glucose was a result of a rapid, 27% fall in glucose output and a 33% rise in glucose uptake. Subsequent stabilization was a result of a return of glucose output and uptake to basal levels. The rebound increment in glucose output was significant (P < 0.05) by 30 min after initiation of the insulin infusion and preceded, by 30-45 min, a significant rise in circulating counterregulatory hormones. With the lower insulin infusion dose, plasma insulin rose two- to threefold, plasma glucose initially fell at a rate of 0.37±0.04 mg/min for 75 min and stabilized at 67±3 mg/dl after 75 min. The changes in plasma glucose were entirely a result of a fall in glucose output and subsequent return to base line, whereas glucose uptake remained unchanged. Plasma levels of counterregulatory hormones showed no change from basal throughout the insulin infusion. In the diabetic group (plasma glucose levels 227±7 mg/dl in the basal state), the initial rate of decline in plasma glucose (1.01±0.15 mg/dl) and the plateau concentration of plasma glucose (59±5 mg/dl) were comparable to controls receiving the same insulin dose. However, the initial fall in plasma glucose was almost entirely a result of

  6. Efficacy of Postoperative Pain Management Using Continuous Local Anesthetic Infusion at the Iliac Crest Bone Graft Site in Patients with Adolescent Idiopathic Scoliosis: A Parallel, Double-Blinded, Randomized Controlled Pilot Trial.

    PubMed

    Samartzis, Dino; Bow, Cora; Cheung, Jason Pui Yin; Sham, Phoebe; Mak, Kin-Cheung; Cheung, Wai-Yuen; Wong, Yat-Wa; Luk, Keith D K; Cheung, Kenneth M C; Lawmin, Jean-Claude

    2016-05-01

    Study Design Randomized controlled trial. Objective Adolescent idiopathic scoliosis (AIS) is a common spinal deformity that affects every population. In severe deformity, surgical intervention is performed. Autogenous iliac crest bone graft (ICBG) harvesting remains a common procedure worldwide for scoliosis surgery. Postoperative pain at the ICBG donor site is a major concern in patients undergoing spine surgery that affects postoperative functional outcome and consumes health care resources. Previous studies have noted a decrease in pain and postoperative analgesic use with the application of continuous infusion of anesthetic at the ICBG site in comparison with placebo. However, there is lack of evidence addressing the efficacy of continuous anesthetic infusion at the ICBG site in young patients and in particular those with spinal deformity, such as AIS. As such, this parallel, double-blinded, randomized controlled trial addressed the pain management efficacy of continuous anesthetic infusion versus saline at the ICBG site in patients with AIS during the immediate postoperative period. Methods Participants were randomized into two groups. Group A (control subjects) received 3 mL per hour of saline locally at the ICBG site, and group B (treatment subjects) received a constant rate of infusion of 3 mL per hour of 0.25% levobupivacaine. Both groups received their postoperative intervention for 47 hours. All subjects and outcome assessors were blinded to the type of intervention. Utilizing the visual analog pain scale, pain was assessed at the primary spine surgical site, ICBG site, and contralateral ICBG site. Overall physical pain was assessed by the McGill Pain Questionnaire. The degree of analgesic use and complications were also evaluated. All outcomes were assessed up until the fourth day of the patients' hospitalization following surgery. Results Twelve subjects were recruited (five in group A; seven in group B). No difference was noted at baseline

  7. Regulation of the insulin-like growth factor system by insulin in burn patients.

    PubMed

    Lang, C H; Fan, J; Frost, R A; Gelato, M C; Sakurai, Y; Herndon, D N; Wolfe, R R

    1996-07-01

    The aim of the present investigation was to determine whether there is a net uptake of insulin-like growth factor I (IGF-I) or IGF-binding proteins (IGFBPs) by the leg after burn injury and to elucidate the regulatory role of insulin exerted on this system under in vivo conditions in burn patients. Studies were performed on nine patients after burn injury (approximately 60% body surface area). Each patient was studied twice during a continuous infusion of a carbohydrate-rich enteral diet. Blood was collected simultaneously from the femoral artery and vein for the measurement of various elements of the IGF system after 7 days of enteral diet alone (basal period) and after 7 days of the enteral diet plus the infusion of insulin (insulin period). Data from these patients were compared to values in age-matched fed healthy volunteers. During the basal period, burn patients demonstrated a significant reduction in the venous concentration of IGF-I and an increase in both IGFBP-1 and -2 compared to control values. Insulin produced a significant 15% increase in the IGF-I concentration in burn patients, but decreased the circulating levels of IGFBP-1 by 50%. The IGF-I and IGFBP-1 concentrations at the end of the insulin period were still significantly different from those in control subjects. Burn patients also exhibited a marked reduction in intact IGFBP-3 and the acid-labile subunit under basal conditions, and these alterations were not reversed by insulin. Under basal conditions, all burn patients had a positive arterio-venous (A-V) difference for IGF-I across the leg. The A-V difference was increased 50% in response to insulin. The net uptake of IGF-I by the leg was 2.4 micrograms/min under basal conditions, and as leg blood flow also tended to increase in response to insulin, IGF-I uptake was elevated more than 3-fold during the insulin period. No A-V difference across the leg was detected for IGFBP-1, -2, or -3 in burn patients. In conclusion, burn injury in humans

  8. Postoperative continuous wound infusion of ropivacaine has comparable analgesic effects and fewer complications as compared to traditional patient-controlled analgesia with sufentanil in patients undergoing non-cardiac thoracotomy

    PubMed Central

    Liu, Fang-Fang; Liu, Xiao-Ming; Liu, Xiao-Yu; Tang, Jun; Jin, Li; Li, Wei-Yan; Zhang, Li-Dong

    2015-01-01

    Objective: To compare the postoperative analgesic effects of continuous wound infusion of ropivacaine with traditional patient-controlled analgesia (PCA) with sufentanil after non-cardiac thoracotomy. Methods: One hundred and twenty adult patients undergoing open thoracotomy were recruited into this assessor-blinded, randomized study. Patients were randomly assigned to receive analgesia through a wound catheter placed below the fascia and connected to a 2 ml/h ropivacaine 0.5% (RWI group) or sufentanil PCA (SPCA group). Analgesia continued for 48 h. Visual analogue scores (VAS) at rest and movement, Ramsay scores and adverse effects were recorded at 2, 8, 12, 24, 36 and 48 h after surgery. Three months after discharge, patient’s satisfaction, residual pain and surgical wound complications were assessed. Results: General characteristics of patients were comparable between two groups. There were no statistical differences in the VAS scores and postoperative pethidine consumption between two groups (P > 0.05). However, when compared with SPCA group, the incidences of drowsiness, dizziness and respiratory depression, ICU stay and hospital expenditure reduced significantly in RWI group (P < 0.05). Patients’ satisfaction with pain management was also improved markedly in RWI group (P < 0.05). Conclusion: Continuous wound infusion with ropivacaine is effective for postoperative analgesia and has comparable effects to traditional PCA with sufentanil. Furthermore, this therapy may also reduce the incidences of drowsiness, dizziness, respiratory depression and decrease the ICU stay and hospital expenditure. PMID:26131121

  9. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital and Personal Use Therapeutic Devices § 880.5725 Infusion pump. (a) Identification....

  10. Suppression in the secretion of follicle-stimulating hormone and luteinizing hormone, and ovarian follicle development in heifers continuously infused with a gonadotropin-releasing hormone agonist.

    PubMed

    Gong, J G; Campbell, B K; Bramley, T A; Gutierrez, C G; Peters, A R; Webb, R

    1996-07-01

    A novel experimental model was developed in cattle to investigate the requirement for FSH and LH during ovarian follicle growth and development. On Day 5 of the estrous cycle, 7 heifers were each implanted with an osmotic minipump containing a GnRH agonist (GnRHa), Buserelin (release rate, 2.5 micrograms/h). Another 7 heifers served as controls. Each minipump was replaced 28 days later with a second pump, which was left in place for a further 20 days. Blood samples were collected daily throughout the experimental period, and frequent samples were also collected on both days of minipump insertion and at 10 days after insertion of the second pump. The ovaries of all heifers were scanned daily by real-time ultrasonography to monitor follicular dynamics. All controls displayed 2 or 3 waves of FSH and follicular development per estrous cycle during the experiment. Insertion of the first minipump produced a large LH and FSH surge and induced ovulation in all 7 animals. Within 8 days of the start of treatment, serum LH concentrations fell to basal levels; they then remained constant at this level throughout the infusion period, only beginning to recover 4-5 days after the termination of infusion. After the initial increase, FSH returned to basal levels before showing a normal wave that was coincident with the emergence, growth, and regression of a dominant follicle. However, despite the peak levels of FSH, dominant follicles from the next wave failed to grow beyond 7-9 mm; they remained at this size for 3 wk until 3-4 days after insertion of the second minipump, when FSH fell precipitously to reach low levels that were maintained throughout the remainder of the infusion. After this fall in FSH concentrations, these follicles regressed rapidly, and no antral follicles > 4 mm were detected until after the termination of treatment. Thereafter, FSH concentrations increased significantly; the increase was accompanied by the emergence of a follicular wave and development of a

  11. Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term insulin resistance

    PubMed Central

    Sjøberg, Kim A; Rattigan, Stephen; Jeppesen, Jacob F; Lundsgaard, Anne-Marie; Holst, Jens J; Kiens, Bente

    2015-01-01

    Abstract Acute infusion of glucagon-like peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. A high fat diet induces impairments in insulin-mediated microvascular recruitment (MVR) and muscle glucose uptake, and here we examined whether this could be reversed by GLP-1. Using contrast-enhanced ultrasound, microvascular recruitment was assessed by continuous real-time imaging of gas-filled microbubbles in the microcirculation after acute (5 days) and prolonged (8 weeks) high fat diet (HF)-induced insulin resistance in rats. A euglycaemic hyperinsulinaemic clamp (3 mU min−1 kg−1), with or without a co-infusion of GLP-1 (100 pmol l−1), was performed in anaesthetized rats. Consumption of HF attenuated the insulin-mediated MVR in both 5 day and 8 week HF interventions which was associated with a 50% reduction in insulin-mediated glucose uptake compared to controls. Acute administration of GLP-1 restored the normal microvascular response by increasing the MVR after both 5 days and 8 weeks of HF intervention (P < 0.05). This effect of GLP-1 was associated with a restoration of both whole body insulin sensitivity and increased insulin-mediated glucose uptake in skeletal muscle by 90% (P < 0.05) after 5 days of HF but not after 8 weeks of HF. The present study demonstrates that GLP-1 increases MVR in rat skeletal muscle and can reverse early stages of high fat diet-induced insulin resistance in vivo. Key points Acute glucagon-like peptide-1 (GLP-1) infusion reversed the high fat diet-induced microvascular insulin resistance that occurred after both 5 days and 8 weeks of a high fat diet intervention. When GLP-1 was co-infused with insulin it had overt effects on whole body insulin sensitivity as well as insulin-mediated skeletal muscle glucose uptake after 5 days of a high fat diet, but not after 8 weeks of high fat diet intervention. Acute GLP-1 infusion did not have an additive

  12. Glucagon-like peptide 1 recruits muscle microvasculature and improves insulin's metabolic action in the presence of insulin resistance.

    PubMed

    Chai, Weidong; Zhang, Xingxing; Barrett, Eugene J; Liu, Zhenqi

    2014-08-01

    Glucagon-like peptide 1 (GLP-1) acutely recruits muscle microvasculature, increases muscle delivery of insulin, and enhances muscle use of glucose, independent of its effect on insulin secretion. To examine whether GLP-1 modulates muscle microvascular and metabolic insulin responses in the setting of insulin resistance, we assessed muscle microvascular blood volume (MBV), flow velocity, and blood flow in control insulin-sensitive rats and rats made insulin-resistant acutely (systemic lipid infusion) or chronically (high-fat diet [HFD]) before and after a euglycemic-hyperinsulinemic clamp (3 mU/kg/min) with or without superimposed systemic GLP-1 infusion. Insulin significantly recruited muscle microvasculature and addition of GLP-1 further expanded muscle MBV and increased insulin-mediated glucose disposal. GLP-1 infusion potently recruited muscle microvasculature in the presence of either acute or chronic insulin resistance by increasing muscle MBV. This was associated with an increased muscle delivery of insulin and muscle interstitial oxygen saturation. Muscle insulin sensitivity was completely restored in the presence of systemic lipid infusion and significantly improved in rats fed an HFD. We conclude that GLP-1 infusion potently expands muscle microvascular surface area and improves insulin's metabolic action in the insulin-resistant states. This may contribute to improved glycemic control seen in diabetic patients receiving incretin-based therapy. PMID:24658303

  13. Adenosine reversal of in vivo hepatic responsiveness to insulin.

    PubMed

    McLane, M P; Black, P R; Law, W R; Raymond, R M

    1990-01-01

    Modulation by adenosine of hepatic responsiveness to insulin was investigated in vivo in 10 healthy mongrel dogs of both sexes by determining net hepatic glucose output (NHGO) in response to insulin during the presence or absence of exogenous adenosine infusion. In addition, two separate series of experiments were performed to study the effect of adenosine (n = 7) or glucagon (n = 5) on NHGO. Basal NHGO, quantitated via the Fick principle, was significantly decreased by insulin infusion (4 U/min; 4.8 +/- 0.6 vs. -1.7 +/- 2.6 mg.kg-1.min-1, P less than 0.05). The addition of an intrahepatic arterial infusion of adenosine (10 mumol/min) during insulin infusion caused glucose output to return to basal levels (insulin, -1.7 +/- 2.6 mg.kg-1.min-1; insulin + adenosine, 3.8 +/- 1.6 mg.kg-1.min-1, P less than 0.05). The addition of intrahepatic arterial saline (control) during insulin infusion had no effect on insulin's action (insulin, -1.0 +/- 1.9 mg.kg-1.min-1; insulin + saline, -1.2 +/- 1.6 mg.kg-1.min-1, P greater than 0.05). Hepatic glucose, lactate, and oxygen deliveries were not affected during either insulin or insulin plus adenosine infusion. Intrahepatic arterial infusion of adenosine alone had no effect on NHGO, whereas intrahepatic arterial infusion of glucagon alone stimulated glucose output approximately fivefold (basal, 2.7 +/- 0.4 mg.kg-1.min-1; glucagon, 15.5 +/- 1.2 mg.kg-1.min-1, P less than 0.01). These results show that adenosine completely reversed the inhibition by insulin of NHGO. These data suggest that adenosine may act as a modulator of insulin action on the liver. PMID:2210062

  14. Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

    PubMed Central

    Drouet, Maryline; Chai, Feng; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal

    2014-01-01

    Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity. PMID:25421476

  15. New Insulin Delivery Recommendations.

    PubMed

    Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

    2016-09-01

    Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes. PMID:27594187

  16. Method of infusion extraction

    NASA Technical Reports Server (NTRS)

    Chang-Diaz, Franklin R. (Inventor)

    1989-01-01

    Apparatus and method of removing desirable constituents from an infusible material by infusion extraction, where a piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, and where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber.

  17. Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep.

    PubMed Central

    Van Cauter, E; Blackman, J D; Roland, D; Spire, J P; Refetoff, S; Polonsky, K S

    1991-01-01

    To define the roles of circadian rhythmicity (intrinsic effects of time of day independent of the sleep or wake condition) and sleep (intrinsic effects of the sleep condition, irrespective of the time of day) on the 24-h variation in glucose tolerance, eight normal men were studied during constant glucose infusion for a total of 53 h. The period of study included 8 h of nocturnal sleep, 28 h of continuous wakefulness, and 8 h of daytime sleep. Blood samples for the measurement of glucose, insulin, C-peptide, cortisol, and growth hormone were collected at 20-min intervals throughout the entire study. Insulin secretion rates were derived from C-peptide levels by deconvolution. Sleep was polygraphically monitored. During nocturnal sleep, levels of glucose and insulin secretion increased by 31 +/- 5% and 60 +/- 11%, respectively, and returned to baseline in the morning. During sleep deprivation, glucose levels and insulin secretion rose again to reach a maximum at a time corresponding to the beginning of the habitual sleep period. The magnitude of the rise above morning levels averaged 17 +/- 5% for glucose and 49 +/- 8% for calculated insulin secretion. Serum insulin levels did not parallel the circadian variation in insulin secretion, indicating the existence of an approximate 40% increase in insulin clearance during the night. Daytime sleep was associated with a 16 +/- 3% rise in glucose levels, a 55 +/- 7% rise in insulin secretion, and a 39 +/- 5% rise in serum insulin. The diurnal variation in insulin secretion was inversely related to the cortisol rhythm, with a significant correlation of the magnitudes of their morning to evening excursions. Sleep-associated rises in glucose correlated with the amount of concomitant growth hormone secreted. These studies demonstrate previously underappreciated effects of circadian rhythmicity and sleep on glucose levels, insulin secretion, and insulin clearance, and suggest that these effects could be partially mediated by

  18. Fluid delivery from infusion-pump syringes.

    PubMed

    Carl, J L; Erstad, B L; Murphy, J E; Slack, M K

    1995-07-01

    Fluid-delivery rates of five small-volume infusion-pump syringes were compared. The study consisted of a comparison of the infusion-pump syringes in their respective infusion pumps (1) set for continuous delivery at 1 mL/hr, (2) set for continuous delivery at 3 mL/hr, and (3) set to deliver 1-mL bolus volumes during continuous delivery at 4 mL/hr. The Life-care prefilled 30-mL syringe (Abbott), the DBL 30-mL syringe no. 770205 (DBL Inc.), and the Pump-Jet 30-mL syringe no. 1931 (International Medication Systems) were tested in the Lifecare PCA Plus II infusion pump no. 4100 (Abbott). The 30-mL Pump-Jet syringe no. 1911 (International Medication Systems) and the DBL 30-mL syringe no. 709700 (DBL Inc.) were tested in the Stratofuse PCA infusion pump (Baxter). The infusion pumps were set to deliver fluid continuously at 1 mL/hr for 30 hours, and the solutions were collected separately and weighed. The procedure was repeated with the infusion rate set at 3 mL/hr for 10 hours. For the third part of the study, each syringe was tested to deliver 1-mL boluses with 0, 5, 15, and 25 mL removed from the syringe. The solutions were collected and weighed before and after each bolus was delivered. The volume of solution collected was calculated by using the specific gravity of the solution. The syringes delivered significantly different volumes during the first hour of infusion at both the 1- and 3-mL/hr rates. Differences also existed across time for most of the syringes. Bolus volumes varied greatly after infusion of 0 or 5 mL of fluid but were acceptable for the remainder of the infusions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7671041

  19. Devices for insulin administration.

    PubMed

    Selam, J L; Charles, M A

    1990-09-01

    There is a significant need for revised, safe, and more effective insulin-delivery methods than subcutaneous injections in the treatment of both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes. The aim of this review is to describe the rationale and methods for better use of injection and infusion devices for intensive insulin therapy and to describe results of animal and human research that will lead to an implantable artificial pancreas. Injection devices, e.g., jet injectors, insulin pens, and access ports, cannot be considered as a major breakthrough in the quest for improved control, although they may improve the patient's comfort. External pumps have benefits over multiple injections and conventional insulin therapy only in specific subgroups of patients, e.g., those with recurrent severe hypoglycemia, but only when used by experienced personnel. The external artificial pancreas (Biostator) is also to be used by experienced personnel for limited clinical and research applications, e.g., surgery of the diabetic patient. The development of an implantable version of the artificial pancreas is linked to progress in the field of reliable long-duration glucose sensors. Finally, programmable implantable insulin pumps, used as an open-loop delivery system, are the most promising alternative to intensive subcutaneous insulin strategies in the short term, although clear evidence of improved safety and efficacy remains to be documented. PMID:2226111

  20. [Portable elastomeric infusion system applied to patients with knee prosthesis].

    PubMed

    Soler, Gemma; Quiles, Olga; Nicolau, Agnes; Faura, Teresa; Moreno, Cristina

    2007-03-01

    An LV infuser consists of an infusion pump which can administer medicines via various methods: intravenous, epidural, subdural, o subcutaneous. Its usefulness is based on the administration of medicines such as oncological drugs and/or analgesic by means of a continuous infusion. PMID:17474369

  1. Methimazole-induced insulin autoimmune syndrome

    PubMed Central

    Jain, Nidhi; Savani, Malvi; Agarwal, Manyoo; Kadaria, Dipen

    2016-01-01

    Background: Hypoglycemia in a critical care setting is often multifactorial with iatrogenic insulin use, sulfonylurea (SU) use, sepsis, adrenal insufficiency and insulinoma among the common causes. Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by the presence of insulin-binding autoantibodies to the sulfhydryl group-containing agents. We report a case of methimazole-induced IAS managed in the intensive care unit. Case presentation: A 76-year-old woman with a history of primary hyperthyroidism was sent from a nursing home for unresponsiveness. Vital signs were significant for hypotension (74/46) and low blood sugars. Fluid resuscitations with normal saline and 50% dextrose stabilized the blood pressure (BP) to 135/75 and her blood glucose to 264. Due to respiratory distress and septic appearance, she required emergency intubation. Nursing home medications were noted for methimazole and absence of any insulin or SU use. Empiric antibiotic treatment was started and fluid resuscitation was continued while home medications were held. Her laboratory values were significant for elevated creatinine, lactic acid, serum cortisol, C-peptide, and insulin. Her cultures, SU screen and computerized tomography (CT) scan were negative for significant findings. On day 2, in addition to 10% dextrose, octreotide was initiated for recurrent hypoglycemia. Her blood glucose (BG) continued to drop throughout the day for which she required glucagon support and a D20 infusion. By day 4, the rate of infusion was titrated up and her BG continued to drop to <60 mg/dl despite D20, octreotide and tube feeds with concentrated calories (1.5 cal/ml). Due to her declining health, her family endorsed palliative care and she was extubated. After day 11, her hypoglycemic episodes resolved and she remained endogenously euglycemic. Conclusions: IAS is associated with methimazole use due to formation of autoantibodies to insulin after its interaction with Sulfhydryl (SH

  2. Insulin therapies: Current and future trends at dawn.

    PubMed

    Yaturu, Subhashini

    2013-02-15

    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

  3. 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

  4. Protracted results of dose-intensive therapy using cyclophosphamide, carmustine, and continuous infusion etoposide with autologous stem cell support in patients with relapse or refractory Hodgkin's disease: a phase II study from the North American Marrow Transplant Group.

    PubMed

    Fleming, D R; Wolff, S N; Fay, J W; Brown, R A; Lynch, J P; Bolwell, B J; Stevens, D A; Goodman, S A; Greer, J P; Stein, R S; Pineiro, L A; Collins, R H; Goldsmith, L J; Herzig, G P; Herzig, R H

    1999-09-01

    To determine the long-term results of high-dose chemotherapy and stem cell support in relapsed or primary refractory Hodgkin disease patients. One hundred and thirty-one patients with relapsed or primary refractory Hodgkin's disease were treated with a dose-intensive therapy protocol consisting of etoposide (2400 mg/m2 continuous intravenous infusion) cyclophosphamide (7200 mg/m2 intravenously), and carmustine (300-600 mg/m2 intravenously) CBVi. All patients had previously failed conventional chemoradiotherapy. Severe toxicities were related to infectious, hepatic, and pulmonary complications. Fatal, regimen-related toxicity was 19%; liver and lung dysfunction, as well as infection, were the most frequent problems. Ninety-one (69%) of the patients achieved a complete response (CR) (95% CI = 59% to 75%) after CBVi and autologous stem cell infusion. With a median follow-up of 5.1 years (range 3.0 to 9.5 years), overall and event-free survival are 44% (95% CI = 33% to 47%) and 38% (95% CI = 28% to 46%) respectively. While univariate analysis did not reveal a statistically significant variable to predict a better response, responsiveness to therapy demonstrated a trend. We conclude that CBVi is an effective therapy for relapsed or refractory Hodgkin's disease, producing long-term, durable remissions. PMID:10512166

  5. Insulin therapy in critically ill patients

    PubMed Central

    Ellahham, Samer

    2010-01-01

    Hyperglycemia frequently occurs with acute medical illness, especially among patients with cardiovascular disease, and has been linked to increased morbidity and mortality in critically ill patients. Even patients who are normoglycemic can develop hyperglycemia in response to acute metabolic stress. An expanding body of literature describes the benefits of normalizing hyperglycemia with insulin therapy in hospitalized patients. As a result, both the American Diabetes Association and the American College of Endocrinology have developed guidelines for optimal control of hyperglycemia, specifically targeting critically ill, hospitalized patients. Conventional blood glucose values of 140–180 mg/dL are considered desirable and safely achievable in most patients. More aggressive control to <110 mg/dL remains controversial, but has shown benefits in certain patients, such as those in surgical intensive care. Intravenous infusion is often used for initial insulin administration, which can then be transitioned to subcutaneous insulin therapy in those patients who require continued insulin maintenance. This article reviews the data establishing the link between hyperglycemia and its risks of morbidity and mortality, and describes strategies that have proven effective in maintaining glycemic control in high-risk hospitalized patients. PMID:21191429

  6. External Beam Radiotherapy Plus 24-Hour Continuous Infusion of Gemcitabine in Unresectable Pancreatic Carcinoma: Long-Term Results of a Phase II Study

    SciTech Connect

    Mattiucci, Gian C.; Morganti, Alessio G.; Valentini, Vincenzo; Ippolito, Edy; Alfieri, Sergio; Antinori, Armando; Crucitti, Antonio; D'Agostino, Giuseppe R.; Di Lullo, Liberato; Luzi, Stefano; Mantini, Giovanna; Smaniotto, Daniela; Doglietto, Gian B.; Cellini, Numa

    2010-03-01

    Purpose: To evaluate the efficacy of gemcitabine-based chemoradiation (CT-RT) in treating patients (pts) affected by locally advanced pancreatic cancers (LAPC). Methods and Materials: Weekly gemcitabine (100 mg/m{sup 2}) was given as a 24-hour infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). After CT-RT, pts received five cycles of sequential chemotherapy with gemcitabine (1000 mg/m{sup 2}; 1, 8, q21). Response rate was assessed according to World Health Organization criteria 6 weeks after the end of CT-RT. Local control (LC), time to progression (TTP), metastases-free survival (MFS), and overall survival (OS) were analyzed by the Kaplan Meier method. Results: Forty pts (male/female 22/18; median age 62 years, range, 36-76) were treated from 2000 to 2005. The majority had T4 tumour (n = 34, 85%), six pts (15%) had T3 tumour. Sixteen pts (40%) were node positive at diagnosis. Grade 3-4 acute toxicity was observed in 21 pts (52.5%). Thirty pts (75%) completed the treatment schedule. A clinical response was achieved in 12 pts (30%). With a median follow-up of 76 months (range, 32-98), 2-year LC was 39.6% (median, 12 months), 2-year TTP was 18.4% (median, 10 months), and 2-year MFS was 29.7% (median, 10 months). Two-year OS (25%; median, 15.5 months) compared with our previous study on 5-fluorouracil-based CT-RT (2.8%) was significantly improved (p <0.001). Conclusions: Gemcitabine CT-RT seems correlated with improved outcomes. Healthier patients who are likely to complete the treatment schedule may benefit most from this therapy.

  7. Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat.

    PubMed

    McGinn, B J; Morrison, J D

    2016-06-28

    Experiments have been undertaken to determine the extent to which cholic acid conjugates of insulin were absorbed from the small intestine of anaesthetised rats by means of the bile salt transporters of the ileum. The measure used to assess the absorption of the cholyl-insulins was the amount of hypoglycaemia following infusion into the small intestine. Control experiments involving infusion of natural insulin into the ileum showed either nil absorption or absorption of a small amount of insulin as indicated by transient dip in the blood glucose concentration. However, when insulin was co-infused with the bile salt taurocholate, this was followed by a marked hypoglycaemic response which was specific to the ileum and did not occur on infusion into the jejunum. When the two cholyl conjugates of insulin were tested viz. B(29)-Lys-cholyl-insulin and B(1)-Phe-cholyl-insulin, both were biologically active as indicated by hypoglycaemic responses on systemic injection, though their potency was about 40% of that of natural insulin. While there was no evidence for the absorption of B(29)-Lys-cholyl-insulin when infused into the ileum, B(1)-Phe-cholyl-insulin did cause a long lasting hypoglycaemic response, indicating that absorption had occurred. Since the hypoglycaemic response was blocked on co-infusion with taurocholate and was absent for infusion of the conjugate into the jejunum, these results were taken as evidence that B(1)-Phe-cholyl-insulin had been taken up by the ileal bile salt transporters. This would indicate that B(1)-Phe-cholyl-insulin is worthy of further investigation for use in an oral insulin formulation. PMID:27084488

  8. Implementing and maintaining an infusion alliance.

    PubMed

    Meyer, Britt M

    2010-01-01

    Infusion therapy models are ever changing and growing in modern health care. New technologies and problems arise daily as researchers and clinicians explore our world. As technologies advance, health care costs are also skyrocketing. The vast majority of hospitalized patients will receive some form of infusion therapy during their stay, and many will continue to receive therapy after they are discharged from the inpatient setting. Infusion alliances can aid cost containment by decreasing infusion-related complication rates, affect customer satisfaction, and promote interdisciplinary collaboration. This article discusses the potential benefits of an infusion alliance, details steps for using the performance improvement process when implementing and maintaining an alliance, and outlines the components of a successful business plan. PMID:20841983

  9. 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

  10. Insulin-induced localized lipoatrophy preceded by shingles (herpes zoster): a case report

    PubMed Central

    2014-01-01

    Introduction Localized involutional lipoatrophy of subcutaneous adipose tissue may develop due to subcutaneous injection of pharmaceutical preparations. The pathogenesis of this adverse drug reaction is unknown. The progression of localized involutional lipoatrophy ceases and occasionally it resolves after withdrawing the inducing agent. In case of localized involutional lipoatrophy due to subcutaneous insulin therapy, low-dose systemic corticosteroids may be curative despite ongoing insulin administration. Case presentation We report a recurrence of insulin-induced localized involutional lipoatrophy at the abdominal wall in a 57-year-old Caucasian woman with type-1 diabetes on continuous subcutaneous insulin infusion. The first episode of insulin-induced localized involutional lipoatrophy two years previously had been cured by oral prednisone. The recurrence was treated immediately with 10mg prednisone once daily for five months, and was cured thereafter. The insulin analog preparation (Humalog™) and the insulin pump equipment (Accu-Chek Spirit™) applied were the same during both episodes. Both episodes were preceded by a temporary disturbance of the immune balance (the first episode by vaccination, the second episode through shingles). Conclusions This case confirms that insulin-induced localized involutional lipoatrophy in type-1 diabetes can occur again, and can be cured by systemic corticosteroids. We suggest that temporary disturbance of the immune balance may trigger this transitory idiosyncratic reaction in a susceptible individual. PMID:24961832

  11. Alternative Devices for Taking Insulin

    MedlinePlus

    ... continuous glucose monitoring (CGM) system an insulin delivery system a computer program that adjusts insulin delivery based on changes in glucose levels CGM systems approved by the U.S. Food and Drug Administration ( ...

  12. Enhanced insulin secretion responsiveness and islet adrenergic desensitization after chronic norepinephrine suppression is discontinued in fetal sheep.

    PubMed

    Chen, Xiaochuan; Green, Alice S; Macko, Antoni R; Yates, Dustin T; Kelly, Amy C; Limesand, Sean W

    2014-01-01

    Intrauterine growth-restricted (IUGR) fetuses experience prolonged hypoxemia, hypoglycemia, and elevated norepinephrine (NE) concentrations, resulting in hypoinsulinemia and β-cell dysfunction. Previously, we showed that acute adrenergic blockade revealed enhanced insulin secretion responsiveness in the IUGR fetus. To determine whether chronic exposure to NE alone enhances β-cell responsiveness afterward, we continuously infused NE into fetal sheep for 7 days and, after terminating the infusion, evaluated glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-induced insulin secretion (GPAIS). During treatment, NE-infused fetuses had greater (P < 0.05) plasma NE concentrations and exhibited hyperglycemia (P < 0.01) and hypoinsulinemia (P < 0.01) compared with controls. GSIS during the NE infusion was also reduced (P < 0.05) compared with pretreatment values. GSIS and GPAIS were approximately fourfold greater (P < 0.01) in NE fetuses 3 h after the 7 days that NE infusion was discontinued compared with age-matched controls or pretreatment GSIS and GPAIS values of NE fetuses. In isolated pancreatic islets from NE fetuses, mRNA concentrations of adrenergic receptor isoforms (α1D, α2A, α2C, and β1), G protein subunit-αi-2, and uncoupling protein 2 were lower (P < 0.05) compared with controls, but β-cell regulatory genes were not different. Our findings indicate that chronic exposure to elevated NE persistently suppresses insulin secretion. After removal, NE fetuses demonstrated a compensatory enhancement in insulin secretion that was associated with adrenergic desensitization and greater stimulus-secretion coupling in pancreatic islets. PMID:24253046

  13. Influence of Acarbose on Plasma Glucose Fluctuations in Insulin-Treated Patients with Type 2 Diabetes: A Pilot Study

    PubMed Central

    Li, Feng-fei; Xu, Xiao-hua; Fu, Li-yuan; Su, Xiao-fei; Wu, Jin-dan; Lu, Chun-feng; Ye, Lei; Ma, Jian-hua

    2015-01-01

    Background and Aims. To evaluate the effect of adding acarbose on glycemic excursions measured by continuous glucose monitoring system (CGMS) in patients with type 2 diabetes mellitus (T2DM) already on insulin therapy. Materials and Methods. This was an opened and unblended study. 134 patients with T2DM were recruited. After initial rapidly corrected hyperglycaemia by continuous subcutaneous insulin infusion (CSII) for 7 d, a 4–6-day premixed insulin titration period subsequently followed. Patients were then randomized 1 : 1 to acarbose plus insulin group or insulin therapy group for 2 weeks. CGMS was used to measure glucose fluctuations for at least 3 days after therapy cessation. Results. Patients in acarbose plus insulin group achieved a significant improvement of MAGE compared to that of insulin therapy only group (5.56 ± 2.16 versus 7.50 ± 3.28 mmol/L, P = 0.044), accompanied by a significant decrease in the incremental AUC of plasma glucose concentration above 10.0 mmol/L (0.5 [0.03, 0.9] versus 0.85 [0.23,1.4]  mmol/L per day, P = 0.037). Conclusions. Add-on acarbose to insulin therapy further improves glucose fluctuation in patients with T2DM. This study was registered with ClinicalTrials.gov registration number ChiCTR-TRC-11001218. PMID:26640487

  14. 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

  15. Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice.

    PubMed

    Ahlkvist, Linda; Omar, Bilal; Valeur, Anders; Fosgerau, Keld; Ahrén, Bo

    2016-03-01

    Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized; however, the effect of long-term GCGR activation on β-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2 weeks) infused with the stable glucagon analog ZP-GA-1 and challenged with oral glucose and intravenous glucose±glucagon-like peptide 1 (GLP1). Islets were isolated to evaluate the insulin secretory response to glucose±GLP1 and their pancreas were collected for immunohistochemical analysis. Two weeks of ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges in vivo and in isolated islets. These inhibitory effects were corrected for by GLP1. Also, we observed increased β-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of β-cell function during development of type 2 diabetes. PMID:26698567

  16. Stimulation of body weight increase and epiphyseal cartilage growth by insulin like growth factor

    NASA Technical Reports Server (NTRS)

    Ellis, S.

    1981-01-01

    The ability of insulin-like growth factor (IGF) to induce growth in hypophysectomized immature rats was tested by continuous infusion of the partially purified factor at daily doses of 6, 21, and 46 mU for an 8-day period. A dose-dependent growth of the proximal epiphyseal cartilage of the tibia and an associated stimulation of the primary spongiosa were produced by these amounts of IGF. The two highest doses of IGF also resulted in dose-dependent increases of body weight. Gel permeation of the sera at neutrality showed that the large-molecular-weight IGF binding protein was not induced by the infusion of IGF, whereas it ws generated in the sera of hypophysectomized rats that were infused with daily doses of 86 mU of human growth hormone.

  17. Programmable physiological infusion

    NASA Technical Reports Server (NTRS)

    Howard, W. H.; Young, D. R.; Adachi, R. R. (Inventor)

    1974-01-01

    A programmable physiological infusion device and method are provided wherein a program source, such as a paper tape, is used to actuate an infusion pump in accordance with a desired program. The system is particularly applicable for dispensing calcium in a variety of waveforms.

  18. Nocturnal Hypoglycemia: Answering the Challenge With Long-acting Insulin Analogs

    PubMed Central

    Brunton, Stephen A.

    2007-01-01

    Background Nocturnal hypoglycemia may be the most common type of hypoglycemia in individuals with diabetes using insulin and is particularly worrisome because it often goes undetected and may lead to unconsciousness and even death in severe cases. Objectives The prevalence, causes, and consequences of nocturnal hypoglycemia as well as detection and prevention strategies are reviewed, including the use of long-acting insulin analogs, which offer more physiologic and predictable time-action profiles than traditional human basal insulin. Data Sources A total of 307 publications (151 PubMed; 104 Adis; 52 BIOSIS) were reviewed. Review Methods Relevant trials were found by searching for “(detemir OR glargine) AND nocturnal AND (hypoglycemia OR hypoglycaemia) AND diabetes.” To capture trials that may not have specified “nocturnal” in the title or abstract text but still reported nocturnal hypoglycemia data, a supplemental search of PubMed using “(detemir OR glargine) AND (nocturnal OR hypoglycemia OR hypoglycaemia) AND diabetes” was undertaken. Results A review of these trials found that patients with type 1 and type 2 diabetes mellitus have a lower risk for nocturnal hypoglycemia when receiving long-acting insulin analogs (insulin detemir or insulin glargine), provided that glycemic control is comparable to that provided by traditional human basal insulin. Long-acting insulin analogs may be the best option to provide basal insulin coverage in patients who do not choose or require continuous subcutaneous insulin infusion. Conclusions Randomized clinical trials suggest that the long-acting insulin analogs are associated with a lower risk for nocturnal hypoglycemia than neutral protamine Hagedorn without sacrificing glycemic control. PMID:17955093

  19. Ovarian tumors secreting insulin.

    PubMed

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  20. Sodium-retaining effect of insulin in diabetes

    PubMed Central

    Manhiani, M. Marlina

    2012-01-01

    Insulin has long been hypothesized to cause sodium retention, potentially of enough magnitude to contribute to hypertension in obesity, metabolic syndrome, and Type II diabetes. There is an abundance of supportive evidence from correlational analyses in humans, acute insulin infusion studies in humans and animals, and chronic insulin infusion studies in rats. However, the absence of hypertension in human insulinoma patients, and negative results for sodium-retaining or blood pressure effects of chronic insulin infusion in a whole series of dog studies, strongly refute the insulin hypothesis. We recently questioned whether the euglycemic, hyperinsulinemia model used for most insulin infusion studies, including the previous chronic dog studies, was the most appropriate model to test the renal actions of insulin in obesity, metabolic syndrome, and Type II diabetes. In those circumstances, hyperinsulinemia coexists with hyperglycemia. Therefore, we tested the sodium-retaining effect of insulin in chronically instrumented, alloxan-treated diabetic dogs. We used 24 h/day intravenous insulin infusion to regulate plasma insulin concentration. Induction of diabetes (∼400 mg/dl) caused sustained natriuresis and diuresis. However, if we clamped insulin at baseline, control levels, i.e., prevented it from decreasing, then the sustained natriuresis and diuresis were completely reversed, despite the same level of hyperglycemia. We also found that 24 h/day intrarenal insulin infusion had the same effect in diabetic dogs but had no sodium-retaining action in normal dogs. This new evidence that insulin has a sodium-retaining effect during hyperglycemia may have implications for maintaining sodium balance in uncontrolled Type II diabetes. PMID:23034715

  1. When Intensive Insulin Therapy (MDI) Fails in Patients With Type 2 Diabetes: Switching to GLP-1 Receptor Agonist Versus Insulin Pump.

    PubMed

    Cohen, Ohad; Filetti, Sebastiano; Castañeda, Javier; Maranghi, Marianna; Glandt, Mariela

    2016-08-01

    Treatment with insulin, alone or with oral or injectable hypoglycemic agents, is becoming increasingly common in patients with type 2 diabetes. However, approximately 40% of patients fail to reach their glycemic targets with the initially prescribed regimen and require intensification of insulin therapy, which increases the risks of weight gain and hypoglycemia. Many of these patients eventually reach a state in which further increases in the insulin dosage fail to improve glycemic control while increasing the risks of weight gain and hypoglycemia. The recently completed OpT2mise clinical trial showed that continuous subcutaneous insulin infusion (CSII) is more effective in reducing glycated hemoglobin (HbA1c) than intensification of multiple daily injection (MDI) insulin therapy in patients with type 2 diabetes who do not respond to intensive insulin therapy. CSII therapy may also be useful in patients who do not reach glycemic targets despite multidrug therapy with basal-bolus insulin and other agents, including glucagon-like peptide (GLP)-1 receptor agonists; current guidelines offer no recommendations for the treatment of such patients. Importantly, insulin and GLP-1 receptor agonists have complementary effects on glycemia and, hence, can be used either sequentially or in combination in the initial management of diabetes. Patients who have not previously failed GLP-1 receptor agonist therapy may show reduction in weight and insulin dose, in addition to moderate improvement in HbA1c, when GLP-1 receptor agonist therapy is added to MDI regimens. In subjects with long-standing type 2 diabetes who do not respond to intensive insulin therapies, switching from MDI to CSII and/or the addition of GLP-1 receptor agonists to MDI have the potential to improve glycemic control without increasing the risk of adverse events. PMID:27440831

  2. Continuous infusion or subcutaneous injection of granulocyte-macrophage colony-stimulating factor: increased efficacy and reduced toxicity when given subcutaneously.

    PubMed Central

    Honkoop, A. H.; Hoekman, K.; Wagstaff, J.; van Groeningen, C. J.; Vermorken, J. B.; Boven, E.; Pinedo, H. M.

    1996-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a haematopoietic growth factor with a wide variety of applications in the clinic. In early phase I studies the continuous intravenous (c.i.) route of administration was often used. Later it was shown that subcutaneous (s.c.) administration was also effective. The optimal route of administration remains, however, poorly defined, and no studies have made a direct comparison between these two routes of administration. We treated patients with advanced breast cancer with moderately high-dose doxorubicin and cylophosphamide and GM-CSF. The first 14 patients received GM-CSF by c.i, while subsequently 47 patients received it s.c. Comparison between the two groups showed that c.i. GM-CSF was more toxic in several respects. There was a higher need for erythrocyte and platelet transfusions and a significant deterioration in the performance status. This study indicates that subcutaneous GM-CSF is the preferred route of administration. Randomised trials are, however, needed to confirm these conclusions. PMID:8855987

  3. 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

  4. Insulin Neuroprotection and the Mechanisms

    PubMed Central

    Yu, Li-Yun; Pei, Yu

    2015-01-01

    Objective: To analyze the mechanism of neuroprotection of insulin and which blood glucose range was benefit for insulin exerting neuroprotective action. Data Sources: The study is based on the data from PubMed. Study Selection: Articles were selected with the search terms “insulin”, “blood glucose”, “neuroprotection”, “brain”, “glycogen”, “cerebral ischemia”, “neuronal necrosis”, “glutamate”, “γ-aminobutyric acid”. Results: Insulin has neuroprotection. The mechanisms include the regulation of neurotransmitter, promoting glycogen synthesis, and inhibition of neuronal necrosis and apoptosis. Insulin could play its role in neuroprotection by avoiding hypoglycemia and hyperglycemia. Conclusions: Intermittent and long-term infusion insulin may be a benefit for patients with ischemic brain damage at blood glucose 6–9 mmol/L. PMID:25836621

  5. A submaximal dose of insulin promotes net skeletal muscle protein synthesis in patients with severe burns.

    PubMed Central

    Ferrando, A A; Chinkes, D L; Wolf, S E; Matin, S; Herndon, D N; Wolfe, R R

    1999-01-01

    OBJECTIVE: To investigate the hypothesis that a submaximal insulin dose reverses the net muscle catabolism associated with severe burns, and to determine its effects on amino acid kinetics. SUMMARY BACKGROUND DATA: The authors previously showed that a maximal dose of insulin administered to patients with severe burns promoted skeletal muscle glucose uptake and net protein synthesis. However, this treatment was associated with caloric overload resulting from the large quantities of exogenous glucose required to maintain euglycemia, and hypoglycemia was a potential problem. METHODS: Thirteen patients were studied after severe burn injury (>60% total body surface area). Patients were randomly treated by standard care (n = 5) or with exogenous insulin (n = 8). Data were derived from an arteriovenous model with primed-continuous infusions of stable isotopes and biopsies of the vastus lateralis muscle. RESULTS: Net amino acid balance was significantly improved with insulin treatment. Skeletal muscle protein synthesis was significantly greater in the group receiving insulin, whereas muscle protein breakdown was not different between the groups. This submaximal dose of insulin did not affect glucose or amino acid uptake or require a greater caloric intake to avoid hypoglycemia. CONCLUSIONS: Submaximal insulin can promote muscle anabolism without eliciting a hypoglycemic response. PMID:9923795

  6. 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

  7. 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

    -DOSE INSULIN. Animal models have shown high-dose insulin to be superior to calcium salts, glucagon, epinephrine, and vasopressin in terms of survival. Currently, there are no published controlled clinical trials in humans, but a review of case reports and case series supports the use of high-dose insulin as an initial therapy. HIGH-DOSE INSULIN TREATMENT PROTOCOLS. When first introduced, insulin doses were cautiously initiated at 0.5 U/kg bolus followed by a 0.5-1 U/kg/h continuous infusion due to concern for hypoglycemia and electrolyte imbalances. With increasing clinical experience and the publication of animal studies, high-dose insulin dosing recommendations have been increased to 1 U/kg insulin bolus followed by a 1-10 U/kg/h continuous infusion. Although the optimal regimen is still to be determined, bolus doses up to 10 U/kg and continuous infusions as high as 22 U/kg/h have been administered with good outcomes and minimal adverse events. ADVERSE EFFECTS OF HIGH-DOSE INSULIN. The major anticipated adverse events associated with high-dose insulin are hypoglycemia and hypokalemia. Glucose concentrations must be monitored regularly and supplementation of glucose will likely be required throughout therapy and for up to 24 h after discontinuation of high-dose insulin. The change in serum potassium concentrations reflects a shifting of potassium from the extracellular to intracellular space rather than a decrease in total body stores. CONCLUSIONS. While more clinical data are needed, animal studies and human case reports demonstrate that high-dose insulin (1-10 U/kg/hour) is a superior treatment in terms of safety and survival in both beta-blocker and calcium-channel blocker poisoning. High-dose insulin should be considered initial therapy in these poisonings. PMID:21563902

  8. Xylitol prevents NEFA-induced insulin resistance in rats

    PubMed Central

    Kishore, P.; Kehlenbrink, S.; Hu, M.; Zhang, K.; Gutierrez-Juarez, R.; Koppaka, S.; El-Maghrabi, M. R.

    2013-01-01

    Aims/hypothesis Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar alcohol xylitol has been shown to have favourable metabolic effects in various animal models. Furthermore, its derivative xylulose 5-phosphate may prevent NEFA-induced suppression of glycolysis. We therefore examined whether and how xylitol might prevent NEFA-induced insulin resistance. Methods We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5-fold elevations in NEFA levels were induced with Intralipid/heparin infusions during 5 h euglycaemic–hyperinsulinaemic clamp studies in 24 conscious non-diabetic Sprague-Dawley rats, with or without infusion of xylitol. Results Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly through suppression of glycogen synthesis. Co-infusion of xylitol prevented the NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although glycolysis was increased by xylitol infusion alone, there was minimal NEFA-induced suppression of glycolysis, which was not affected by co-infusion of xylitol. Conclusions/interpretation We conclude that xylitol prevented NEFA-induced insulin resistance, with favourable effects on glycogen synthesis accompanying the improved insulin-mediated glucose uptake. This suggests that this pentose sweetener has beneficial insulin-sensitising effects. PMID:22460760

  9. Comparison of Intrahepatic and Pancreatic Perfusion on Fusion Images Using a Combined SPECT/CT System and Assessment of Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy in Advanced Pancreatic Carcinoma

    SciTech Connect

    Ikeda, Osama Tamura, Yoshitaka; Nakasone, Yutaka; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Yamashita, Yasuyuki; Takamori, Hiroshi; Kanemitsu, Keiichiro; Baba, Hideo

    2007-09-15

    Purpose. The purpose of this study was to compare intrahepatic and pancreatic perfusion on fusion images using a combined single-photon emission computed tomography (SPECT)/CT system and to evaluate the efficacy of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in the treatment of advanced pancreatic carcinoma. Materials and Methods. CTAI was performed in 33 patients (22 men, 11 women; age range, 35-77 years; mean age, 60 years) with stage IV pancreatic cancer with liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. In all patients we obtained fusion images using a combined SPECT/CT system. Pancreatic perfusion on fusion images was classified as perfusion presence or as perfusion absent in the pancreatic cancer. Using WHO criteria we recorded the tumor response after 3 months on multislice helical CT scans. Treatment effects were evaluated based on the pancreatic cancer, liver metastasis, and factors such as intrahepatic and pancreatic perfusion on fusion images. For statistical analysis we used the chi-square test; survival was evaluated by the Kaplan Meier method (log-rank test). Results. On fusion images, pancreatic and intrahepatic perfusion was recorded as hot spot and as homogeneous distribution, respectively, in 18 patients (55%) and as cold spot and heterogeneous distribution, respectively, in 15 (45%). Patients with hot spot in the pancreatic tumor and homogeneous distribution in the liver manifested better treatment results (p < 0.05 and p < 0.01, respectively). Patients with hot spot both in the pancreatic cancer and in the liver survived longer than those with cold spot in the pancreatic cancer and heterogeneous distribution in the liver (median {+-} SD, 16.0 {+-} 3.7 vs. 8.0 {+-} 1.4 months; p < 0.05). Conclusions. We conclude that in patients with advanced

  10. Saline infusion sonohysterography.

    PubMed

    2004-01-01

    Saline infusion sonohysterography consists of ultrasonographic imaging of the uterus and uterocervical cavity, using real-time ultrasonography during injection of sterile saline into the uterus. When properly performed, saline infusion sonohysterography can provide information about the uterus and endometrium. The most common indication for sonohysterography is abnormal uterine bleeding. sonohysterography should not be performed in a woman who is pregnant or could be pregnant or in a woman with a pelvic infection or unexplained pelvic tenderness. Physicians who perform or supervise diagnostic saline infusion sonohysterograpy should have training, experience, and demonstrated competence in gynecologic ultrasonography and saline infusion sonohysterography. Portions of this document were developed jointly with the American College of Radiology and the American Institute of Ultrasound in Medicine. PMID:14968760

  11. Fluid infusion system

    NASA Technical Reports Server (NTRS)

    1974-01-01

    Performance testing carried out in the development of the prototype zero-g fluid infusion system is described and summarized. Engineering tests were performed in the course of development, both on the original breadboard device and on the prototype system. This testing was aimed at establishing baseline system performance parameters and facilitating improvements. Acceptance testing was then performed on the prototype system to verify functional performance. Acceptance testing included a demonstration of the fluid infusion system on a laboratory animal.

  12. Exogenous Insulin Enhances Glucose-Stimulated Insulin Response in Healthy Humans Independent of Changes in Free Fatty Acids

    PubMed Central

    Lopez, Ximena; Cypess, Aaron; Manning, Raquel; O'Shea, Sheila; Kulkarni, Rohit N.

    2011-01-01

    Context: Islet β-cells express both insulin receptors and insulin signaling proteins. Recent studies suggest insulin signaling is physiologically important for glucose sensing. Objective: Preexposure to insulin enhances glucose-stimulated insulin secretion (GSIS) in healthy humans. We evaluated whether the effect of insulin to potentiate GSIS is modulated through regulation of free fatty acids (FFA). Design and Setting: Subjects were studied on three occasions in this single-site study at an academic institution clinical research center. Patients: Subjects included nine healthy volunteers. Interventions: Glucose-induced insulin response was assessed on three occasions after 4 h saline (low insulin/sham) or isoglycemic-hyperinsulinemic (high insulin) clamps with or without intralipid and heparin infusion, using B28 Asp-insulin that could be distinguished from endogenous insulin immunologically. During the last 80 min of all three clamps, additional glucose was administered to stimulate insulin secretion (GSIS) with glucose concentrations maintained at similar concentrations during all studies. Main Outcome Measure: β-Cell response to glucose stimulation was assessed. Results: Preexposure to exogenous insulin increased the endogenous insulin-secretory response to glucose by 32% compared with sham clamp (P = 0.001). This was accompanied by a drop in FFA during hyperinsulinemic clamp compared with the sham clamp (0.06 ± 0.02 vs. 0.60 ± 0.09 mEq/liter, respectively), which was prevented during the hyperinsulinemic clamp with intralipid/heparin infusion (1.27 ± 0.17 mEq/liter). After preexposure to insulin with intralipid/heparin infusion to maintain FFA concentration, GSIS was 21% higher compared with sham clamp (P < 0.04) and similar to preexposure to insulin without intralipid/heparin (P = 0.2). Conclusions: Insulin potentiates glucose-stimulated insulin response independent of FFA concentrations in healthy humans. PMID:21956413

  13. Effects of intraduodenal administration of HCl and glucose on circulating immunoreactive secretin and insulin concentrations.

    PubMed

    Boden, G; Essa, N; Owen, O E; Reichle, F A

    1974-04-01

    . The metabolic clearance rate was 730+/-34 ml/min, volume of distribution was 17.4+/-0.8% of body weight, and the half-life of disappearance was 2.8+/-0.1 min. It could be calculated that 1.38 U/kg-h(-1) of endogenous secretin was released into the peripheral circulation during the steady state period of the HCl infusion experiments. The data indicated that immunoreactive secretin was released rapidly after intestinal acidification, continued to be secreted throughout the duration of HCl infusion, and was promptly distributed in the extracellular compartment. Furthermore, they suggested that endogenously released secretin could stimulate insulin secretion. The HCl-mediated insulinogenic effect of immunoreactive secretin, however, was too weak to influence peripheral immunoreactive insulin, glucose, and free fatty acid concentrations. The failure of intraduodenal glucose to stimulate secretin release suggests that secretin is not the insulin-stimulatory factor released from the gastrointestinal tract in response to glucose. PMID:4815082

  14. Effects of Intraduodenal Administration of HCl and Glucose on Circulating Immunoreactive Secretin and Insulin Concentrations

    PubMed Central

    Boden, Guenther; Essa, Noorjehan; Owen, Oliver E.; Reichle, Frederick A.; Saraga, Walter

    1974-01-01

    . The metabolic clearance rate was 730±34 ml/min, volume of distribution was 17.4±0.8% of body weight, and the half-life of disappearance was 2.8±0.1 min. It could be calculated that 1.38 U/kg-h-1 of endogenous secretin was released into the peripheral circulation during the steady state period of the HCl infusion experiments. The data indicated that immunoreactive secretin was released rapidly after intestinal acidification, continued to be secreted throughout the duration of HCl infusion, and was promptly distributed in the extracellular compartment. Furthermore, they suggested that endogenously released secretin could stimulate insulin secretion. The HCl-mediated insulinogenic effect of immunoreactive secretin, however, was too weak to influence peripheral immunoreactive insulin, glucose, and free fatty acid concentrations. The failure of intraduodenal glucose to stimulate secretin release suggests that secretin is not the insulin-stimulatory factor released from the gastrointestinal tract in response to glucose. Images PMID:4815082

  15. Insulin structure and function.

    PubMed

    Mayer, John P; Zhang, Faming; DiMarchi, Richard D

    2007-01-01

    Throughout much of the last century insulin served a central role in the advancement of peptide chemistry, pharmacology, cell signaling and structural biology. These discoveries have provided a steadily improved quantity and quality of life for those afflicted with diabetes. The collective work serves as a foundation for the development of insulin analogs and mimetics capable of providing more tailored therapy. Advancements in patient care have been paced by breakthroughs in core technologies, such as semisynthesis, high performance chromatography, rDNA-biosynthesis and formulation sciences. How the structural and conformational dynamics of this endocrine hormone elicit its biological response remains a vigorous area of study. Numerous insulin analogs have served to coordinate structural biology and biochemical signaling to provide a first level understanding of insulin action. The introduction of broad chemical diversity to the study of insulin has been limited by the inefficiency in total chemical synthesis, and the inherent limitations in rDNA-biosynthesis and semisynthetic approaches. The goals of continued investigation remain the delivery of insulin therapy where glycemic control is more precise and hypoglycemic liability is minimized. Additional objectives for medicinal chemists are the identification of superagonists and insulins more suitable for non-injectable delivery. The historical advancements in the synthesis of insulin analogs by multiple methods is reviewed with the specific structural elements of critical importance being highlighted. The functional refinement of this hormone as directed to improved patient care with insulin analogs of more precise pharmacology is reported. PMID:17410596

  16. Insulin sensitivity and metabolic clearance rate of insulin in familial multiple lipomatosis.

    PubMed

    Garcia Lopez, J M; Murias Taboada, E; Torre Carballada, J A; Vidal Vazquez, P; Iglesias Guerrero, M; Cabezas-Cerrato, J

    1988-01-01

    Intolerance to glucose in certain kinds of lipomatosis is well documented. This article describes a euglucaemic hyperinsulinaemic clamp study of alterations in glucose and/or insulin metabolism in four members of a single family with familial multiple lipomatosis. Fifteen normal subjects were studied as controls. The four patients exhibited no alteration in tolerance to orally administered glucose. When a Biostator Glucose-Controlled Insulin Infusion System (GCIIS) was used to clamp glycaemia at 4.44 mmol/L with successive insulin infusion rates of (a) 0.5 (b) 1.0 or (c) 5.0 mU/kg/min, there was no difference between patients and controls as regards the value of M, the rate of glucose infusion, but the concentrations of immunoreactive insulin recorded during the last 40 minutes of each phase of the clamp were greater in patients than in controls (45 +/- 2 vs 27 +/- 2 uU/mL (p less than 0.01), 83 +/- 2 vs 60 +/- 5 uU/mL (p less than 0.05) and 537 +/- 48 vs 377 +/- 25 uU/mL (p less than 0.05) for insulin infusion rates (a), (b) and (c) respectively), and the ratio M/IRI was consequently smaller for patients than controls (1.92 +/- 0.41 vs 3.06 +/- 0.19 (p less than 0.05) for an insulin infusion rate of 5 mU/kg/min). The metabolic clearance rate of insulin was likewise slower in patients than controls (p less than 0.01). It is concluded that the four patients studied (all members of the same family) have sub-normal sensitivity to insulin secondary to a sub-normal metabolic clearance rate for insulin. PMID:3044865

  17. Fluid infusion system

    NASA Technical Reports Server (NTRS)

    Hammond, J. C.

    1975-01-01

    Development of a fluid infusion system was undertaken in response to a need for an intravenous infusion device operable under conditions of zero-g. The initial design approach, pursued in the construction of the first breadboard instrument, was to regulate the pressure of the motive gas to produce a similar regulated pressure in the infusion liquid. This scheme was not workable because of the varying bag contact area, and a major design iteration was made. A floating sensor plate in the center of the bag pressure plate was made to operate a pressure regulator built into the bellows assembly, effectively making liquid pressure the directly controlled variable. Other design changes were made as experience was gained with the breadboard. Extensive performance tests were conducted on both the breadboard and the prototype device; accurately regulated flows from 6 m1/min to 100 m1/min were achieved. All system functions were shown to operate satisfactorily.

  18. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  19. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  20. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  1. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  2. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  3. Comparative metabolic effects of acetate and dichloroacetate infusion in the anesthetized dog.

    PubMed

    Ward, R A; Wathen, R L; Harding, G B; Thompson, L C

    1985-07-01

    The comparative effects of acetate (10 mmol/h/kg) and dichloroacetate (DCA) (1 mmol/h/kg and 10 mmol/h/kg) on acid-base and intermediary metabolism were assessed using the fasted anesthetized dog, undergoing controlled ventilation, as a metabolic model. Infusion of acetate resulted in a marked metabolic alkalemia and a decline in PaO2, while DCA had minimal effects on acid-base state and oxygen consumption. Serum glucose decreased with both DCA and acetate infusion, although only significantly with the latter. At infusion rates of 10 mmol/h/kg, acetate caused marked decreases, while DCA caused marked increases, in serum potassium and phosphorus. Acetate and DCA also had opposing effects on lactate and citrate levels, the former caused increases and the latter decreases in both metabolites. Pyruvate levels decreased similarly in response to both infusates. Acetoacetate and beta-hydroxybutyrate levels increased significantly with both acetate and DCA infusions; however, the increases were much greater with acetate than with DCA infusion. Blood alanine levels decreased significantly during the infusion of both acetate and DCA, whereas, free fatty acids tended to increase with acetate infusion, remained unchanged with low dose DCA and fell significantly with high dose DCA. Plasma insulin levels were sustained during acetate infusion, but fell abruptly with termination of infusion. In contrast, insulin levels fell markedly with DCA infusion and remained depressed throughout the infusion and recovery periods. Blood levels of acetate and DCA rose markedly during infusion; however, while acetate levels decreased nearly to control values during the recovery period, DCA levels remained elevated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3925292

  4. Pioglitazone Increases Whole Body Insulin Sensitivity in Obese, Insulin-Resistant Rhesus Monkeys

    PubMed Central

    Tozzo, Effie; Bhat, Gowri; Cheon, Kyeongmi; Camacho, Raul C.

    2015-01-01

    Hyperinsulinemic-euglycemic clamps are considered the "gold standard" for assessing whole body insulin sensitivity. When used in combination with tracer dilution techniques and physiological insulin concentrations, insulin sensitization can be dissected and attributed to hepatic and peripheral (primarily muscle) effects. Non-human primates (NHPs), such as rhesus monkeys, are the closest pre-clinical species to humans, and thus serve as an ideal model for testing of compound efficacy to support translation to human efficacy. We determined insulin infusion rates that resulted in high physiological insulin concentrations that elicited maximal pharmacodynamic responses during hyperinsulinemic-euglycemic clamps. These rates were then used with [U-13C]-D-glucose, to assess and document the degrees of hepatic and peripheral insulin resistance between healthy and insulin-resistant, dysmetabolic NHPs. Next, dysmetabolic NHPs were treated for 28 days with pioglitazone (3 mg/kg) and again had their insulin sensitivity assessed, illustrating a significant improvement in hepatic and peripheral insulin sensitivity. This coincided with a significant increase in insulin clearance, and normalization of circulating adiponectin. In conclusion, we have determined a physiological clamp paradigm (similar to humans) for assessing glucose turnover in NHPs. We have also demonstrated that insulin-resistant, dysmetabolic NHPs respond to the established insulin sensitizer, pioglitazone, thus confirming their use as an ideal pre-clinical translational model to assess insulin sensitizing compounds. PMID:25954816

  5. Glucose metabolism in non-diabetic and insulin-dependent diabetic subjects with end-stage renal failure.

    PubMed

    Schmitz, O

    1991-02-01

    Chronic uremia is frequently associated with an impaired carbohydrate tolerance. During the past decade considerable progress have been made in characterizing and quantifying this biochemical abnormality in end-stage renal failure (ESRF). Primarily, this has been possible by means of the glucose clamp technique which basically makes it possible to evaluate insulin sensitivity and glucose-stimulated insulin secretion. Combined with the use of tracer dilution technique, hepatic vein catheterization technique, infusion of somatostatin, forearm or leg techniques and indirect calorimetry, insight into several other major parameters of glucose kinetics has been achieved; i.e. insulin-mediated glucose uptake (IMGU), glucose-induced glucose uptake (GIGU), hepatic glucose production (HGP) splanchnic glucose uptake and oxidative and nonoxidative glucose disposal. Of course, these extra facets make the clamp procedure less feasible to accomplish for technical reasons and demand an extensive knowledge of the limitations of these methods. One major factor behind the reduced glucose tolerance in uremia is an impaired sensitivity to insulin (insulin resistance) in peripheral tissues, mainly in skeletal muscle. In non-dialysed uremic patients the insulin dose-response curve is characterized by a decreased maximal response and by a rightward shift. In general, the insulin resistance is pronounced, but a few weeks on maintenance hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) are enough to improve insulin action significantly. Occasionally, IMGU has been found normal in patients on long-term HD. In contrast to insulin-stimulated glucose uptake, basal glucose turnover is normal in patients with ESRF. The ability of glucose to enhance its own uptake is difficult to measure in human studies, because even small amounts of insulin is able to modulate GIGU profoundly. At basal insulinemia, however, GIGU is markedly impaired in uremia. Recently, it has been suggested

  6. Importance of peripheral insulin levels for insulin-induced suppression of glucose production in depancreatized dogs.

    PubMed Central

    Giacca, A; Fisher, S J; Shi, Z Q; Gupta, R; Lickley, H L; Vranic, M

    1992-01-01

    It is generally believed that glucose production (GP) cannot be adequately suppressed in insulin-treated diabetes because the portal-peripheral insulin gradient is absent. To determine whether suppression of GP in diabetes depends on portal insulin levels, we performed 3-h glucose and specific activity clamps in moderately hyperglycemic (10 mM) depancreatized dogs, using three protocols: (a) 54 pmol.kg-1 bolus + 5.4 pmol.kg-1.min-1 portal insulin infusion (n = 7; peripheral insulin = 170 +/- 51 pM); (b) an equimolar peripheral infusion (n = 7; peripheral insulin = 294 +/- 28 pM, P < 0.001); and (c) a half-dose peripheral infusion (n = 7), which gave comparable (157 +/- 13 pM) insulinemia to that seen in protocol 1. Glucose production, use (GU) and cycling (GC) were measured using HPLC-purified 6-[3H]- and 2-[3H]glucose. Consistent with the higher peripheral insulinemia, peripheral infusion was more effective than equimolar portal infusion in increasing GU. Unexpectedly, it was also more potent in suppressing GP (73 +/- 7 vs. 55 +/- 7% suppression between 120 and 180 min, P < 0.001). At matched peripheral insulinemia (protocols 2 and 3), not only stimulation of GU, but also suppression of GP was the same (55 +/- 7 vs. 63 +/- 4%). In the diabetic dogs at 10 mM glucose, GC was threefold higher than normal but failed to decrease with insulin infusion by either route. Glycerol, alanine, FFA, and glucagon levels decreased proportionally to peripheral insulinemia. However, the decrease in glucagon was not significantly greater in protocol 2 than in 1 or 3. When we combined all protocols, we found a correlation between the decrements in glycerol and FFAs and the decrease in GP (r = 0.6, P < 0.01). In conclusion, when suprabasal insulin levels in the physiological postprandial range are provided to moderately hyperglycemic depancreatized dogs, suppression of GP appears to be more dependent on peripheral than portal insulin concentrations and may be mainly mediated by

  7. Insulin formulations--a review.

    PubMed

    Gualandi-Signorini, A M; Giorgi, G

    2001-01-01

    Although the improvement on insulin therapy since it was first conceived, it is still far from mimicking physiological secretion of pancreatic b-cells and research to find new insulin formulations and new routes of administration continues. Human biosynthetic insulin (rapid-acting, intermediate-acting and long-acting), produced by recombinant DNA technique, is currently available. The pharmacokinetic profile of rapid-acting insulin (regular) does not adequately reproduce the physiological post-prandial insulin response. This has led to the development of molecular analogues with slight modifications that prevent the spontaneous polymerisation underlying delayed absorption. Fast-acting analogues such as Lyspro and Aspart can be injected immediately before the meal, inducing a very fast and substantial peak of insulin, similar to that produced by b-cells, but have the disadvantage of short duration of action. For this reason, and because of the difficulty of obtaining sufficient basal insulin concentrations to control preprandial blood glucose levels with current long-acting insulins, analogues known as Glargine and Detemir have been synthesized. They have virtually no plasma peak and acts for about 24 h. These characteristics make it ideal to cover basal insulin requirement. With insulin analogues, it also seems possible to overcome the problem of intra- and inter-individual variability in absorption after subcutaneous injection. This variability is directly proportional to the duration of insulin action. Research into new routes of administration has led to production of inhaled insulin powder, soon to become commercially available. Insulin is absorbed through the lung alveoli. Trials to evaluate efficacy and toleration have shown that inhaled insulin has a similar kinetic profile to the fast-acting injected analogue and can therefore be used for mealtime requirement, combined with a single daily injection of long-acting insulin. Oral insulin is currently being

  8. Serum Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor Binding Protein-3 in Obstructive Sleep Apnea Patients: Effect of Continuous Positive Airway Pressure Treatment

    PubMed Central

    Archontogeorgis, Kostas; Nena, Evangelia; Papanas, Nikolaos; Xanthoudaki, Maria; Hatzizisi, Olga; Kyriazis, Georgios; Tsara, Venetia; Maltezos, Efstratios; Froudarakis, Marios; Steiropoulos, Paschalis

    2015-01-01

    Background and Aim: Hypoxia, a major feature of obstructive sleep apnea (OSA), modifies Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels, which contribute to atherogenesis and occurrence of cardiovascular (CV) events. We assessed and compared serum levels of VEGF and IGFBP-3 in newly diagnosed OSA patients and controls, to explore associations with anthropometric and sleep parameters and to study the effect of continuous positive airway pressure (CPAP) treatment on these levels. Materials and Methods: Serum levels of VEGF and IGFBP-3 were measured in 65 OSA patients and 31 age- and body mass index- matched controls. In OSA patients, measurements were repeated after 6 months of CPAP therapy. All participants were non-smokers, without any comorbidities or systemic medication use. Results: At baseline, serum VEGF levels in OSA patients were higher compared with controls (p<0.001), while IGFBP-3 levels were lower (1.41±0.56 vs. 1.61±0.38 μg/ml, p=0.039). VEGF levels correlated with apnea-hypopnea index (r=0.336, p=0.001) and oxygen desaturation index (r=0.282, p=0.007). After 6 months on CPAP treatment, VEGF levels decreased in OSA patients (p<0.001), while IGFBP-3 levels increased (p<0.001). Conclusion: In newly diagnosed OSA patients, serum levels of VEGF are elevated, while IGFBP-3 levels are low. After 6 months of CPAP treatment these levels change. These results may reflect an increased CV risk in untreated OSA patients, which is ameliorated after CPAP therapy. PMID:27006717

  9. Lessons learned from a pilot RCT of simultaneous versus delayed initiation of continuous glucose monitoring in children and adolescents with type 1 diabetes starting insulin pump therapy.

    PubMed

    Olivier, Patricia; Lawson, Margaret L; Huot, Celine; Richardson, Christine; Nakhla, Meranda; Romain, Judette

    2014-05-01

    Uncertainty remains about effectiveness of continuous glucose monitoring (CGM) in pediatric type 1 diabetes (T1D). Success with CGM is related to CGM adherence, which may relate to readiness to make the behavior changes required for effective use. We hypothesize that readiness for change will be greater at initiation of insulin pump therapy than in established pump users, and that this will predict CGM adherence. Our objective was to evaluate the feasibility of a randomized controlled trial (RCT) in children with established T1D comparing simultaneous pump and CGM initiation to standard pump therapy with delayed CGM initiation. We randomized participants to simultaneous pump and CGM initiation or to standard pump therapy with the option of adding CGM 4 months later. CGM adherence was tracked via web-based download and readiness for change assessed with the SOCRATES questionnaire. Of 41 eligible children, 20 agreed to participate; 15 subjects completed the study (7 males; baseline age 11.8 ± 4.0 years; T1D duration 2.7 ± 2.7 years; mean A1C 8.2 ± 0.8%). Six of 8 simultaneous group subjects used CGM > 60% of the time for 4 months compared to 1 of 7 delayed group subjects (P = .02). Using SOCRATES, we could assign 87-100% of subjects to a single motivation stage at baseline and 4 months. This pilot study demonstrates the feasibility of randomizing pump naïve children and adolescents with established T1D to simultaneous pump and CGM initiation versus standard pump therapy with delayed CGM initiation. Lessons from this pilot study were used to inform development of a full-scale multicenter RCT. PMID:24876616

  10. 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

  11. American Diabetes Association. Resource guide 2005. Insulin delivery.

    PubMed

    2005-01-01

    Syringes...pumps...jet injectors...pens...infusers...they all do the same basic thing--deliver insulin. These items carry insulin through the outermost layer of skin and into fatty tissue so it can be used by the body. This section will also cover injection aids, products design to make injecting easier. PMID:15714617

  12. The Importance of Palmitoleic Acid to Adipocyte Insulin Resistance and Whole-Body Insulin Sensitivity in Type 1 Diabetes

    PubMed Central

    Howard, David; Schauer, Irene E.; Maahs, David M.; Snell-Bergeon, Janet K.; Clement, Timothy W.; Eckel, Robert H.; Perreault, Leigh; Rewers, Marian

    2013-01-01

    Context: Type 1 diabetes is an insulin-resistant state, but it is less clear which tissues are affected. Our previous report implicated skeletal muscle and liver insulin resistance in people with type 1 diabetes, but this occurred independently of generalized, visceral, or ectopic fat. Objective: The aim of the study was to measure adipose tissue insulin sensitivity and plasma triglyceride composition in individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose. Design, Patients, and Methods: Fifty subjects (25 individuals with type 1 diabetes and 25 controls without) were studied. After 3 d of dietary control and overnight insulin infusion, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m2 · min. Infusions of [1,1,2,3,3-2H2]glycerol and [1-13C]palmitate were used to quantify lipid metabolism. Results: Basal glycerol and palmitate rates of appearance were similar between groups, decreased more in control subjects during the first two stages of the clamp, and similarly suppressed during the highest insulin dose. The concentration of insulin required for 50% inhibition of lipolysis was twice as high in individuals with type 1 diabetes. Plasma triglyceride saturation was similar between groups, but palmitoleic acid in plasma triglyceride was inversely related to adipocyte insulin sensitivity. Unesterified palmitoleic acid in plasma was positively related to insulin sensitivity in controls, but not in individuals with type 1 diabetes. Conclusions: Adipose tissue insulin resistance is a significant feature of type 1 diabetes. Palmitoleic acid is not related to insulin sensitivity in type 1 diabetes, as it was in controls, suggesting a novel mechanism for insulin resistance in this population. PMID:23150678

  13. Oral Insulin

    PubMed Central

    2010-01-01

    Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation. PMID:21059246

  14. Insulin Resistance, Defective Insulin-Mediated Fatty Acid Suppression, and Coronary Artery Calcification in Subjects With and Without Type 1 Diabetes

    PubMed Central

    Schauer, Irene E.; Snell-Bergeon, Janet K.; Bergman, Bryan C.; Maahs, David M.; Kretowski, Adam; Eckel, Robert H.; Rewers, Marian

    2011-01-01

    OBJECTIVE To assess insulin action on peripheral glucose utilization and nonesterified fatty acid (NEFA) suppression as a predictor of coronary artery calcification (CAC) in patients with type 1 diabetes and nondiabetic controls. RESEARCH DESIGN AND METHODS Insulin action was measured by a three-stage hyperinsulinemic-euglycemic clamp (4, 8, and 40 mU/m2/min) in 87 subjects from the Coronary Artery Calcification in Type 1 Diabetes cohort (40 diabetic, 47 nondiabetic; mean age 45 ± 8 years; 55% female). RESULTS Peripheral glucose utilization was lower in subjects with type 1 diabetes compared with nondiabetic controls: glucose infusion rate (mg/kg FFM/min) = 6.19 ± 0.72 vs. 12.71 ± 0.66, mean ± SE, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and final clamp glucose and insulin. Insulin-induced NEFA suppression was also lower in type 1 diabetic compared with nondiabetic subjects: NEFA levels (μM) during 8 mU/m2/min insulin infusion = 370 ± 27 vs. 185 ± 25, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and time point insulin. Lower glucose utilization and higher NEFA levels, correlated with CAC volume (r = −0.42, P < 0.0001 and r = 0.41, P < 0.0001, respectively) and predicted the presence of CAC (odds ratio [OR] = 0.45, 95% CI = 0.22–0.93, P = 0.03; OR = 2.4, 95% CI = 1.08–5.32, P = 0.032, respectively). Insulin resistance did not correlate with GHb or continuous glucose monitoring parameters. CONCLUSIONS Type 1 diabetic patients are insulin resistant compared with nondiabetic subjects, and the degree of resistance is not related to current glycemic control. Insulin resistance predicts the extent of coronary artery calcification and may contribute to the increased risk of cardiovascular disease in patients with type 1 diabetes as well as subjects without diabetes. PMID:20978091

  15. Intrahippocampal Insulin Improves Memory in a Passive-Avoidance Task in Male Wistar Rats

    ERIC Educational Resources Information Center

    Babri, Shirin; Badie, Hamid Gholamipour; Khamenei, Saeed; Seyedlar, Mehdi Ordikhani

    2007-01-01

    The main impacts of insulin favor the peripheral organs. Although it functions as a neuropeptide, insulin possesses also some central effects. The aim of this study was to determine the effect of intrahippocampal infusion of insulin on passive avoidance learning in healthy male rats. Thirty male wistar rats were divided into three groups (n = 10…

  16. Lipolytic response to glucose infusion in human subjects

    SciTech Connect

    Wolfe, R.R.; Peters, E.J.

    1987-02-01

    The authors have determined the effect of various rates of glucose infusion on the rates of release of glycerol (R/sub a/ glycerol), free fatty acids (R/sub a/ FFA), and on energy metabolism in normal human volunteers. Plasma kinetics were determined with use of the stable isotopic tracers D-5-glycerol and (1- TC)palmitate, and energy metabolism was determined by indirect calorimetry. The effect of glucose infusion on R/sub a/ glycerol and R/sub a/ FFA was dose-dependent. At 4 mg x kg x min , both R/sub a/ glycerol and R/sub a/ FFA were suppressed; at 8 mg x kg x min , R/sub a/ FFA was even more depressed, but R/sub a/ glycerol was similar to the value during the 4 mg x kg x min infusion. At all infusion rates tested, the amount of potential energy available from the sum of the glucose infusion and endogenously mobilized fat was always greater than when no glucose was infused. Glucose decreased fat mobilization by both inhibiting lipolysis and stimulating reesterification, thus causing a significant increase in triglyceride-fatty acid substrate cycling within the adipose tissue. Plasma insulin was determined by radioimmunoassay.

  17. Subcutaneous infusion in palliative care: a focus on the neria soft 90 infusion set.

    PubMed

    Gabriel, Janice

    2014-11-01

    Subcutaneous administration of medications and/or fluids can play a crucial part in supporting patients at home and thereby avoiding the need for hospitalisation. It is an area of patient care that has received little attention compared with other types of parenteral therapies. However, it is an effective and safe route for continuous administration for individuals requiring palliative care. Technological advancements have led to improved subcutaneous infusion devices, such as fine-gauge cannulae with integral sharps protection, as well as integral hypoallergenic dressings. These design features not only help to increase patient comfort but also minimise the potential for needlestick injuries, as well as providing the health professional with one sterile package containing all of the components needed to establish subcutaneous infusion. However, technological developments alone are insufficient to improve patient outcomes. Knowledge of the individual patient, together with their diagnosis and intended treatment, will influence the choice of subcutaneous infusion device, with the overall aim of minimising the potential for complications and improving comfort. This paper provides an overview of subcutaneous infusion, including the importance of patient assessment and the education and training needs of health professionals, and then focuses on one specific subcutaneous infusion device: the neria soft 90 infusion set. PMID:25426880

  18. [Alleged suicide by insulin].

    PubMed

    Birngruber, Christoph G; Krüll, Ralf; Dettmeyer, Reinhard; Verhoff, Marcel A

    2015-01-01

    A 26-year-old man, who was on probation, was found dead in his home by his mother. Insulin vials and 2 insulin pens, which the man's stepfather (an insulin-dependent diabetic) had been missing for over a week, were found next to the deceased. The circumstances suggested suicide by an injected insulin overdose. At the time of the autopsy, the corpse showed already marked signs of autolysis. Clinical chemical tests confirmed the injection of insulin, but indicated hyperglycemia at the time of death. Toxicological analyses revealed that the man had consumed amphetamine, cannabinoids, and tramadol in the recent past. Histological examination finally revealed extensive bronchopneumonia as the cause of death. The most plausible explanation for the results of the autopsy and the additional examinations was an injection of insulin as a failed attempt of self-treatment. It is conceivable that the man had discovered by a rapid test that he was a diabetic, but had decided not to go to a doctor to avoid disclosure of parole violation due to continued drug abuse. He may have misinterpreted the symptoms caused by his worsening bronchitis and the developing bronchopneumonia as symptoms of a diabetic metabolic status and may have felt compelled to treat himself with insulin. PMID:26419091

  19. Using miniature osmotic infusion pumps to maintain tritiated thymidine exposure to cells in culture

    SciTech Connect

    Neely, J.E.; Hake, D.A.

    1982-06-01

    To provide a constant level of tracer doses of tritiated thymidine to cultured cells during continuous infusion, miniature osmotic infusion pumps were used to provide replacement thymidine. By determining the loss of isotope from the media during nonreplacement, the rate of constant infusion replacement to maintain thymidine levels was calculated. The replacement rates were similar for the three cell lines examined and allowed a standard osmotic pump infusion.

  20. A Model of the Kinetics of Insulin in Man

    PubMed Central

    Sherwin, Robert S.; Kramer, Karl J.; Tobin, Jordan D.; Insel, Paul A.; Liljenquist, John E.; Berman, Mones; Andres, Reubin

    1974-01-01

    The design of the present study of the kinetics of insulin in man combines experimental features which obviate two of the major problems in previous insulin studies. (a) The use of radioiodinated insulin as a tracer has been shown to be inappropriate since its metabolism differs markedly from that of the native hormone. Therefore porcine insulin was administered by procedures which raised insulin levels in arterial plasma into the upper physiologic range. Hypoglycemia was prevented by adjusting the rate of an intravenous infusion of glucose in order to control the blood glucose concentration (the glucose-clamp technique). (b) Estimation of a single biological half-time of insulin after pulse injection of the hormone has been shown to be inappropriate since plasma insulin disappearance curves are multiexponential. Therefore the SAAM 25 computer program was used in order to define the parameters of a three compartment insulin model. The combined insulin mass of the three compartments (expressed as plasma equivalent volume) is equal to inulin space (15.7% body wt). Compartment 1 is apparently the plasma space (4.5%). The other two compartments are extra-vascular; compartment 2 is small (1.7%) and equilibrates rapidly with plasma, and compartment 3 is large (9.5%) and equilibrates slowly with plasma. The SAAM 25 program can simulate the buildup and decay of insulin in compartments 2 and 3 which cannot be assayed directly. Insulin in compartment 3 was found to correlate remarkably with the time-course of the servo-controlled glucose infusion. Under conditions of a steady-state arterial glucose level, glucose infusion is a measure of glucose utilization. We conclude that compartment 3 insulin (rather than plasma insulin) is a more direct determinant of glucose utilization. We suggest that the combined use of glucose-clamp and kinetic-modeling techniques should aid in the delineation of pathophysiologic states affecting glucose and insulin metabolism. Images PMID:4856884

  1. Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting, and research needs: a joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group.

    PubMed

    Heinemann, Lutz; Fleming, G Alexander; Petrie, John R; Holl, Reinhard W; Bergenstal, Richard M; Peters, Anne L

    2015-04-01

    Insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII), is an important and evolving form of insulin delivery, which is mainly used for people with type 1 diabetes. However, even with modern insulin pumps, errors of insulin infusion can occur due to pump failure, insulin infusion set (IIS) blockage, infusion site problems, insulin stability issues, user error, or a combination of these. Users are therefore exposed to significant and potentially fatal hazards: interruption of insulin infusion can result in hyperglycemia and ketoacidosis; conversely, delivery of excessive insulin can cause severe hypoglycemia. Nevertheless, the available evidence on the safety and efficacy of CSII remains limited. The European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have therefore joined forces to review the systems in place for evaluating the safety of pumps from a clinical perspective. We found that useful information held by the manufacturing companies is not currently shared in a sufficiently transparent manner. Public availability of adverse event (AE) reports on the US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database is potentially a rich source of safety information but is insufficiently utilized due to the current configuration of the system; the comparable database in Europe (European Databank on Medical Devices [EUDAMED]) is not publicly accessible. Many AEs appear to be attributable to human factors and/or user error, but the extent to which manufacturing companies are required by regulators to consider the interactions of users with the technical features of their products is limited. The clinical studies required by regulators prior to marketing are small and over-reliant on bench testing in relation to "predicate" products. Once a pump is available on the market, insufficient data are made publicly available on its long-term use in a real

  2. Insulin pump risks and benefits: a clinical appraisal of pump safety standards, adverse event reporting and research needs. A joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group.

    PubMed

    Heinemann, Lutz; Fleming, G Alexander; Petrie, John R; Holl, Reinhard W; Bergenstal, Richard M; Peters, Anne L

    2015-05-01

    Insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII), is an important and evolving form of insulin delivery, which is mainly used for people with type 1 diabetes. However, even with modern insulin pumps, errors of insulin infusion can occur due to pump failure, insulin infusion set (IIS) blockage, infusion site problems, insulin stability issues, user error or a combination of these. Users are therefore exposed to significant and potentially fatal hazards: interruption of insulin infusion can result in hyperglycaemia and ketoacidosis; conversely, delivery of excessive insulin can cause severe hypoglycaemia. Nevertheless, the available evidence on the safety and efficacy of CSII remains limited. The European Association for the Study of Diabetes (EASD) and American Diabetes Association (ADA) have therefore joined forces to review the systems in place for evaluating the safety of pumps from a clinical perspective. We found that useful information held by the manufacturing companies is not currently shared in a sufficiently transparent manner. Public availability of adverse event (AE) reports on the US Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database is potentially a rich source of safety information but is insufficiently utilised due to the current configuration of the system; the comparable database in Europe (European Databank on Medical Devices, EUDAMED) is not publicly accessible. Many AEs appear to be attributable to human factors and/or user error, but the extent to which manufacturing companies are required by regulators to consider the interactions of users with the technical features of their products is limited. The clinical studies required by regulators prior to marketing are small and over-reliant on bench testing in relation to 'predicate' products. Once a pump is available on the market, insufficient data are made publicly available on its long-term use in a real

  3. Biosimilar Insulins

    PubMed Central

    Hompesch, Marcus

    2014-01-01

    Until now most of the insulin used in developed countries has been manufactured and distributed by a small number of multinational companies. Beyond the established insulin manufacturers, a number of new players have developed insulin manufacturing capacities based on modern biotechnological methods. Because the patents for many of the approved insulin formulations have expired or are going to expire soon, these not yet established companies are increasingly interested in seeking market approval for their insulin products as biosimilar insulins (BI) in highly regulated markets like the EU and the United States. Differences in the manufacturing process (none of the insulin manufacturing procedures are 100% identical) can lead to insulins that to some extent may differ from the originator insulin. The key questions are if subtle differences in the structure of the insulins, purity, and so on are clinically relevant and may result in different biological effects. The aim of this article is to introduce and discuss basic aspects that may be of relevance with regard to BI. PMID:24876530

  4. Biosimilar insulins.

    PubMed

    Heinemann, Lutz

    2012-08-01

    Until now most insulin used in developed countries is manufactured and distributed by a small number of multinational companies. Other pharmaceutical companies - many of these are located in countries such as India or China - are also able to manufacture insulin with modern biotechnological methods. Additionally, the patents for many insulin formulations have expired or are going to expire soon. This enables such companies to produce insulins and to apply for market approval of these as biosimilar insulins (BIs) in highly regulated markets such as the EU or the US. To understand the complexity of BIs' approval and usage, scientific and regulatory aspects have to be discussed. Differences in the manufacturing process (none of the insulin-manufacturing procedures are identical) result in the fact that all insulin that might become BIs differ from the originator insulin to some extent. The question is, have such differences in the structure of the insulin molecule and or the purity and so on clinically relevant consequences for the biological effects induced or not. The guidelines already in place in the EU for market approval require that the manufacturer demonstrates that his insulin has a safety and efficacy profile that is similar to that of the 'original' insulin formulation. Recently guidelines for biosimilars were issued in the US; however, these do not cover insulin. Although a challenging approval process for insulins to become BI might be regarded as a hurdle to keep companies out of certain markets, it is fair to say that the potential safety and efficacy issues surrounding BI are substantial and relevant, and do warrant a careful and evidence-driven approval process. Nevertheless, it is very likely that in the next years, BIs will come to the market also in highly regulated markets. PMID:22583127

  5. Relaxin Treatment Reverses Insulin Resistance in Mice Fed a High-Fat Diet

    PubMed Central

    Bonner, Jeffrey S.; Lantier, Louise; Hocking, Kyle M.; Kang, Li; Owolabi, Mark; James, Freyja D.; Bracy, Deanna P.; Brophy, Colleen M.; Wasserman, David H.

    2013-01-01

    The endogenous hormone relaxin increases vascular reactivity and angiogenesis. We demonstrate that acute relaxin infusion in lean C57BL/6J mice enhances skeletal muscle perfusion and augments muscle glucose uptake during a hyperinsulinemic-euglycemic clamp. However, an acute effect was absent in mice fed a high-fat (HF) diet for 13 weeks. In contrast, mice fed an HF diet for 13 weeks and continuously treated with relaxin for the final 3 weeks of the diet exhibited decreased fasting blood glucose. Insulin-stimulated whole-body glucose disappearance and percent suppression of hepatic glucose production are corrected by chronic relaxin. The increase in peripheral glucose utilization is a result of augmented in vivo skeletal muscle glucose uptake. Relaxin intervention improves endothelial-dependent vascular reactivity and induces a two-fold proliferation in skeletal muscle capillarity. The metabolic effects of the treatment are not attributed to changes in myocellular insulin signaling. Relaxin intervention reverses the accumulation of collagen III in the liver and collagen III and collagen IV in the heart; this is induced by HF feeding. These studies show the potential of relaxin in the treatment of diet-induced insulin resistance and vascular dysfunction. Relaxin provides a novel therapeutic approach targeting the extramyocellular barriers to insulin action, which are critical to the pathogenesis of insulin resistance. PMID:23801576

  6. Clinical Use of U-500 Regular Insulin: Review and Meta-Analysis

    PubMed Central

    Reutrakul, Sirimon; Wroblewski, Kristen; Brown, Rebecca L.

    2012-01-01

    The use of U-500 regular insulin (U-500R) to treat diabetic patients with severe insulin resistance has increased. In this review, we performed a meta-analysis of PubMed studies reporting the use of U-500R to evaluate the effects of U-500R on hemoglobin A1c (HbA1c), body weight, and total daily insulin dose (TDD). These studies included 310 patients using U-500R as multiple daily injections (MDI) and 55 patients using U-500R via continuous subcutaneous insulin infusion (CSII). Overall, the use of U-500R as MDI resulted in a significant HbA1c reduction of 1.59%, a significant weight gain of 4.38 kg, and a significant increase in TDD by 51.9 units. The use of U-500R via CSII resulted in a similarly significant HbA1c reduction of 1.64% but a nonsignificant weight gain and a nonsignificant change in TDD. The use of U-500 regular insulin both as MDI and via CSII was not reported to be associated with severe hypoglycemia but was associated with an increase in patient satisfaction as well as in cost savings. Suggestions in initiating U-500R in the outpatient setting using U-500R in hospitalized patients are reviewed. In addition, precautions for avoiding prescription and patient errors are discussed. PMID:22538155

  7. Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes

    SciTech Connect

    Serri, O.; Beauregard, H.; Brazeau, P.; Abribat, T.; Lambert, J.; Harris, A.; Vachon, L. Sandoz Canada Inc., Dorval, Quebec )

    1991-02-20

    To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, the authors studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 {mu}g/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group than in the placebo group. Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group than in the placebo group. Glycemic control did not change significantly in either group. They conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

  8. Hepatic transcatheter arterial chemoembolization alternating with systemic protracted continuous infusion 5-fluorouracil for gastrointestinal malignancies metastatic to liver: a phase II trial of the Puget Sound Oncology Consortium (PSOC 1104).

    PubMed

    Bavisotto, L M; Patel, N H; Althaus, S J; Coldwell, D M; Nghiem, H V; Thompson, T; Storer, B; Thomas, C R

    1999-01-01

    We assessed a regimen of alternating regional and systemic therapy in patients with gastrointestinal malignancies with liver-dominant metastases for feasibility, toxicity, response rate, response duration, patterns of progression, and progression-free and overall survival. Regional therapy comprised selective hepatic transcatheter arterial chemoembolization (TACE) using a suspension of cisplatin and particulate polyvinyl alcohol. This procedure was delivered between cycles of protracted continuous infusion 5-fluorouracil (PCI-5FU) as systemic chemotherapy. Patient eligibility criteria included: (a) having histologically documented adenocarcinoma arising from a gastrointestinal primary site with unresectable liver metastases bidimensionally measurable on computerized tomography scan; (b) age greater than 18 years; and (c) performance status 0-2 (Zubrod). PCI-5FU (250 mg/m2/day) was administered i.v. for 28 days, followed by the first TACE (TACE 1) delivered to the hepatic artery supplying the lobe with the greatest tumor burden. Restaging was performed before TACE 2 and TACE 3, which followed at monthly intervals. PCI-5FU for 21 days was sandwiched between each of the TACE treatments. After the final TACE, maintenance PCI-5FU was given for 28 days of each 35-day cycle until toxicity or progression. Between December 23, 1991, and January 19, 1995, 32 patients were registered in this trial, of whom 27 were eligible; 20 completed one or more treatment cycles and were evaluable for radiographic response. Patients with colorectal liver metastases predominated (74%). Twelve (44%) of 27 patients had failed one or more prior treatment regimens. There were no treatment-related deaths, and hematological and hepatic toxicities were generally manageable and reversible. Two patients, however, developed hepatic abscesses requiring drainage, and one patient developed an infarcted gallbladder, which necessitated cholecystectomy. There were no patients with complete responses; there

  9. Multiple Intravenous Infusions Phase 2a: Ontario Survey

    PubMed Central

    Fan, Mark; Koczmara, Christine; Masino, Caterina; Cassano-Piché, Andrea; Trbovich, Patricia; Easty, Anthony

    2014-01-01

    Background Research conducted in earlier phases of this study prospectively identified a number of concerns related to the safe administration of multiple intravenous (IV) infusions in Ontario hospitals. Objective To investigate the potential prevalence of practices or policies that may contribute to the patient safety risks identified in Phase 1b of this study. Data Sources and Review Methods Sixty-four survey responses were analyzed from clinical units where multiple IV infusions may occur (e.g., adult intensive care units). Survey questions were organized according to the topics identified in Phase 1b as potential contributors to patient harm (e.g., labelling practices, patient transfer practices, secondary infusion policies). Results Survey results indicated suboptimal practices and policies in some clinical units, and variability in a number of infusion practices. Key areas of concern included the following: use of primary IV tubing without back check valves when administering secondary infusions administration of secondary infusions with/as high-alert continuous IV medications potential confusion about how IV tubing should be labelled to reflect replacement date and time interruptions to IV therapy due to IV pump and/or tubing changes when patients are transferred between clinical units coadministration of continuous or intermittent infusions on central venous pressure monitoring ports variability in respondents’ awareness of the infusion pump's bolus capabilities Limitations Due to the limited sample size, survey responses may not be representative of infusion practices across Ontario. Answers to some questions indicated that the intent of the questions might have been misunderstood. Due to a design error, 1 question about bolus administration methods was not shown to as many respondents as appropriate. Conclusions The Ontario survey revealed variability in IV infusion practice across the province and potential opportunities to improve safety. PMID

  10. 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

  11. Rapid Pharmacokinetics of Intradermal Insulin Administered Using Microneedles in Type 1 Diabetes Subjects

    PubMed Central

    Gupta, Jyoti

    2011-01-01

    Abstract Background This study compared the pharmacokinetics, postprandial glycemic response, and pain associated with intradermal lispro insulin delivery using a microneedle with that of a conventional catheter. Subjects and Methods Five subjects with type 1 diabetes were administered a bolus infusion of lispro insulin using a 9-mm-long subcutaneous catheter (control treatment) and a 0.9-mm-long microneedle (study treatment), followed by consumption of a standardized meal. Blood samples were periodically assayed for plasma glucose and free insulin levels. Results Intradermal insulin infusion using microneedles reached peak insulin concentrations in approximately half the time and led to greater reduction in plasma glucose levels than subcutaneous catheters. Microneedles were also significantly less painful than the catheters. Conclusion The rapid pharmacokinetics and minimally invasive nature of intradermal insulin infusion using microneedles provide significant potential for improved diabetes management. PMID:21355717

  12. [Intraosseous infusion for adults].

    PubMed

    Leidel, B A; Kirchhoff, C

    2008-04-01

    Intraosseous (IO) infusion methods have been common for emergency treatment in infants and children for years. The role of IO access in adults is however much less clear, but its importance in this patient group is increasing, and different devices are available today. Each device has strengths and weaknesses, but all achieve rapid vascular access even in challenging situations. The potential of IO access regarding both therapeutic and diagnostic options has been shown in several operational studies in and out of hospital. Insertion times require between 1 and 2 min in most cases, while insertion and handling of the IO access devices seem to be easy and reliable. The flow rates of IO access devices for adults are lower than those of large-bore peripheral intravenous catheters, but fluid resuscitation is possible in most cases at least with pressure bag infusion systems. Most drugs administered intravenously can be given intraosseously in equivalent dosages and with the same effects. Nevertheless the limitations and risks of IO access routes need to be considered for each application. Rapid IO access is now possible in all age groups, and the 2005 AHA Guidelines favor it over drug administration via the endotracheal tube. PMID:18250995

  13. Insulin Analogs Versus Human Insulin in the Treatment of Patients With Diabetic Ketoacidosis

    PubMed Central

    Umpierrez, Guillermo E.; Jones, Sidney; Smiley, Dawn; Mulligan, Patrick; Keyler, Trevor; Temponi, Angel; Semakula, Crispin; Umpierrez, Denise; Peng, Limin; Cerón, Miguel; Robalino, Gonzalo

    2009-01-01

    OBJECTIVE To compare the safety and efficacy of insulin analogs and human insulins both during acute intravenous treatment and during the transition to subcutaneous insulin in patients with diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS In a controlled multicenter and open-label trial, we randomly assigned patients with DKA to receive intravenous treatment with regular or glulisine insulin until resolution of DKA. After resolution of ketoacidosis, patients treated with intravenous regular insulin were transitioned to subcutaneous NPH and regular insulin twice daily (n = 34). Patients treated with intravenous glulisine insulin were transitioned to subcutaneous glargine once daily and glulisine before meals (n = 34). RESULTS There were no differences in the mean duration of treatment or in the amount of insulin infusion until resolution of DKA between intravenous treatment with regular and glulisine insulin. After transition to subcutaneous insulin, there were no differences in mean daily blood glucose levels, but patients treated with NPH and regular insulin had a higher rate of hypoglycemia (blood glucose <70 mg/dl). Fourteen patients (41%) treated with NPH and regular insulin had 26 episodes of hypoglycemia and 5 patients (15%) in the glargine and glulisine group had 8 episodes of hypoglycemia (P = 0.03). CONCLUSIONS Regular and glulisine insulin are equally effective during the acute treatment of DKA. A transition to subcutaneous glargine and glulisine after resolution of DKA resulted in similar glycemic control but in a lower rate of hypoglycemia than with NPH and regular insulin. Thus, a basal bolus regimen with glargine and glulisine is safer and should be preferred over NPH and regular insulin after the resolution of DKA. PMID:19366972

  14. Dose-response effect of elevated plasma free fatty acid on insulin signaling.

    PubMed

    Belfort, Renata; Mandarino, Lawrence; Kashyap, Sangeeta; Wirfel, Kelly; Pratipanawatr, Thongchai; Berria, Rachele; Defronzo, Ralph A; Cusi, Kenneth

    2005-06-01

    The dose-response relationship between elevated plasma free fatty acid (FFA) levels and impaired insulin-mediated glucose disposal and insulin signaling was examined in 21 lean, healthy, normal glucose-tolerant subjects. Following a 4-h saline or Liposyn infusion at 30 (n = 9), 60 (n = 6), and 90 (n = 6) ml/h, subjects received a 2-h euglycemic insulin (40 mU . m(-2) . min(-1)) clamp. Basal plasma FFA concentration ( approximately 440 micromol/l) was increased to 695, 1,251, and 1,688 micromol/l after 4 h of Liposyn infusion and resulted in a dose-dependent reduction in insulin-stimulated glucose disposal (R(d)) by 22, 30, and 34%, respectively (all P < 0.05 vs. saline control). At the lowest lipid infusion rate (30 ml/h), insulin receptor and insulin receptor substrate (IRS)-1 tyrosine phosphorylation, phosphatidylinositol (PI) 3-kinase activity associated with IRS-1, and Akt serine phosphorylation were all significantly impaired (P < 0.05-0.01). The highest lipid infusion rate (90 ml/h) caused a further significant reduction in all insulin signaling events compared with the low-dose lipid infusion (P < 0.05-0.01) whereas the 60-ml/h lipid infusion caused an intermediate reduction in insulin signaling. However, about two-thirds of the maximal inhibition of insulin-stimulated glucose disposal already occurred at the rather modest increase in plasma FFA induced by the low-dose (30-ml/h) lipid infusion. Insulin-stimulated glucose disposal was inversely correlated with both the plasma FFA concentration after 4 h of lipid infusion (r = -0.50, P = 0.001) and the plasma FFA level during the last 30 min of the insulin clamp (r = -0.54, P < 0.001). PI 3-kinase activity associated with IRS-1 correlated with insulin-stimulated glucose disposal (r = 0.45, P < 0.01) and inversely with both the plasma FFA concentration after 4 h of lipid infusion (r = -0.39, P = 0.01) and during the last 30 min of the insulin clamp (r = -0.43, P < 0.01). In summary, in skeletal muscle of lean

  15. Insulin resistance and insulin sensitizers.

    PubMed

    Stumvoll, M; Häring, H

    2001-01-01

    Insulin resistance is a key factor in the pathogenesis of type 2 diabetes mellitus and a co-factor in the development of dyslipidaemia, hypertension and atherosclerosis. The causes of insulin resistance include factors such as obesity and physical inactivity, and there may also be genetic factors. The mechanism of obesity-related insulin resistance involves the release of factors from adipocytes which exert a negative effect on glucose metabolism: free fatty acids, tumour necrosis factor-alpha and the recently discovered hormone, resistin. The two resulting abnormalities observed consistently in glucose-intolerant states are impaired suppression of endogenous glucose production, and impaired stimulation of glucose uptake. Among the genetic factors, a polymorphism (Pro12Ala) in the peroxisome proliferator-activated receptor (PPAR) gamma is associated with a reduced risk of type 2 diabetes mellitus and increased insulin sensitivity, primarily that of lipolysis. On the other hand, the association with insulin resistance of a common polymorphism (Gly972Arg) in the insulin receptor substrate 1, long believed to be a plausible candidate gene, is weak at best. This polymorphism may instead be associated with reduced insulin secretion, which, in view of the recent recognition of the insulin signalling system in beta-cells, results in the development of a novel pathogenic concept. Finally, fine-mapping and positional cloning of the susceptibility locus on chromosome 2 resulted in the identification of a polymorphism (UCSNP-43 G/A) in the calpain-10 gene. In non-diabetic Pima Indians, this polymorphism was associated with insulin resistance of glucose disposal. The pharmacological treatment of insulin resistance has recently acquired a novel class of agents: the thiazolidinediones. They act through regulation of PPARgamma-dependent genes and probably interfere favourably with factors released from adipocytes which mediate obesity-associated insulin resistance. PMID:11684868

  16. Multiple Intravenous Infusions Phase 2b: Laboratory Study

    PubMed Central

    Pinkney, Sonia; Fan, Mark; Chan, Katherine; Koczmara, Christine; Colvin, Christopher; Sasangohar, Farzan; Masino, Caterina; Easty, Anthony; Trbovich, Patricia

    2014-01-01

    Background Administering multiple intravenous (IV) infusions to a single patient via infusion pump occurs routinely in health care, but there has been little empirical research examining the risks associated with this practice or ways to mitigate those risks. Objectives To identify the risks associated with multiple IV infusions and assess the impact of interventions on nurses’ ability to safely administer them. Data Sources and Review Methods Forty nurses completed infusion-related tasks in a simulated adult intensive care unit, with and without interventions (i.e., repeated-measures design). Results Errors were observed in completing common tasks associated with the administration of multiple IV infusions, including the following (all values from baseline, which was current practice): setting up and programming multiple primary continuous IV infusions (e.g., 11.7% programming errors) identifying IV infusions (e.g., 7.7% line-tracing errors) managing dead volume (e.g., 96.0% flush rate errors following IV syringe dose administration) setting up a secondary intermittent IV infusion (e.g., 11.3% secondary clamp errors) administering an IV pump bolus (e.g., 11.5% programming errors) Of 10 interventions tested, 6 (1 practice, 3 technology, and 2 educational) significantly decreased or even eliminated errors compared to baseline. Limitations The simulation of an adult intensive care unit at 1 hospital limited the ability to generalize results. The study results were representative of nurses who received training in the interventions but had little experience using them. The longitudinal effects of the interventions were not studied. Conclusions Administering and managing multiple IV infusions is a complex and risk-prone activity. However, when a patient requires multiple IV infusions, targeted interventions can reduce identified risks. A combination of standardized practice, technology improvements, and targeted education is required. PMID:26316919

  17. Treatment of insulin resistance in uremia.

    PubMed

    Stefanović, V; Nesić, V; Stojimirović, B

    2003-02-01

    Insulin resistance is a characteristic feature of uremia. As long as the hyperinsulinemia adequate to overcome the insulin resistance, glucose tolerance remains normal. In patients destined to develop type 2 diabetes, the beta cell compensatory response declines, and relative, or absolute, insulin deficiency develops. At this point glucose intolerance and eventually frank type 2 diabetes occur. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Several studies have confirmed that hemodialysis (HD) treatment significantly improves insulin resistance. Both CAPD and CCPD are shown to improve insulin resistance in uremic patients. Comparing the effect of PD and HD treatment, it was found that the CCPD group has significantly higher insulin sensitivity than the HD group with the CAPD group similar to HD. Treatment of calcium and phosphate disturbances, including vitamin D therapy, significantly reduces insulin resistance in uremia. Treatment with recombinant human erythropoietin (EPO) is an efficient way to increase hematocrit, to reverse cardiovascular problems and to improve insulin sensitivity. Angiotensin-converting enzyme inhibitors have been shown to improve insulin resistance, hyperinsulinemia and glucose intolerance in uremic patients. Thiazolidinediones (TZDs), the new insulin-sensitizing drugs, provide the proof that pharmacologic treatment of insulin resistance can be of enormous clinical benefit. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms. PMID:12653342

  18. Intravenous infusions in chronic pain management.

    PubMed

    Kosharskyy, Boleslav; Almonte, Wilson; Shaparin, Naum; Pappagallo, Marco; Smith, Howard

    2013-01-01

    In the United States, millions of Americans are affected by chronic pain, which adds heavily to national rates of morbidity, mortality, and disability, with an ever-increasing prevalence. According to a 2011 report titled Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research by the Institute of Medicine of the National Academies, pain not only exacts its toll on people's lives but also on the economy with an estimated annual economic cost of at least $560 - 635 billion in health care costs and the cost of lost productivity attributed to chronic pain. Intravenous infusions of certain pharmacologic agents have been known to provide substantial pain relief in patients with various chronic painful conditions. Some of these infusions are better, and although not necessarily the first therapeutic choice, have been widely used and extensively studied. The others show promise, however are in need of further investigations. This article will focus on non-opiate intravenous infusions that have been utilized for chronic painful disorders such as fibromyalgia, neuropathic pain, phantom limb pain, post-herpetic neuralgia, complex regional pain syndromes (CRPS), diabetic neuropathy, and central pain related to stroke or spinal cord injuries. The management of patients with chronic pain conditions is challenging and continues to evolve as new treatment modalities are explored and tested. The following intravenous infusions used to treat the aforementioned chronic pain conditions will be reviewed: lidocaine, ketamine, phentolamine, dexmedetomidine, and bisphosphonates. This overview is intended to familiarize the practitioner with the variety of infusions for patients with chronic pain. It will not, however, be able to provide guidelines for their use due to the lack of sufficient evidence. PMID:23703410

  19. Sex-specific action of insulin to acutely increase the metabolic clearance rate of dehydroepiandrosterone in humans.

    PubMed Central

    Nestler, J E; Kahwash, Z

    1994-01-01

    To test the hypothesis that insulin acutely enhances the metabolic clearance rate (MCR) of dehydroepiandrosterone in humans, the effect of a short-term insulin infusion on the MCR of dehydroepiandrosterone was assessed in 10 men and 7 women. After an overnight fast, dehydroepiandrosterone was infused at 3.47 mumol/h for 6.5 h. At 240 min, a hyperinsulinemic-euglycemic clamp was begun by infusing insulin at 21.5 pmol/kg per min for 2.5 h. MCR of dehydroepiandrosterone was calculated at baseline (210-240 min) and during the insulin infusion (360-390 min). A control study was conducted at least 1 wk later, in which 0.45% saline was substituted for the hyperinsulinemic-euglycemic clamp. During the insulin clamp study, serum insulin rose from 34 +/- 2 to 1084 +/- 136 pmol/liter (P = 0.0001) in men and from 40 +/- 5 to 1357 +/- 175 pmol/liter (P = 0.0003) in women, while serum glucose remained constant in both groups. MCR of dehydroepiandrosterone rose in men during the insulin infusion from 2443 +/- 409 to 3599 +/- 500 liters/24 h (P = 0.003), but did not change during the control saline infusion. In contrast, MCR of dehydroepiandrosterone in women did not change in the insulin clamp study during insulin infusion (2526 +/- 495 liters/24 h at baseline vs. 2442 +/- 491 liters/24 h during insulin infusion; P = 0.78). These findings suggest that insulin acutely increases the MCR of dehydroepiandrosterone in men but not in women. PMID:7929824

  20. [Development of smart infusion system].

    PubMed

    Li, Junyang

    2014-01-01

    The free care smart infusion system which has the function of liquid end alarm and automatic stopping has been designed. In addition, the system can send the alarm to the health care staff by Zigbee wireless network. Besides, the database of infusion information has been set up, it can be used for inquiry afterwards. PMID:24839846

  1. Removing the confusion about infusion.

    PubMed

    Bayne, C G

    1997-02-01

    There is more to infusion technology than simply connecting the "pump-du-jour" to the central line. The purpose of infusion technology, its safety products and four categories of devices-elastomeric, mechanical, gas and membrane-are discussed. PMID:9287736

  2. Heat stress increases insulin sensitivity in pigs

    PubMed Central

    Sanz Fernandez, M Victoria; Stoakes, Sara K; Abuajamieh, Mohannad; Seibert, Jacob T; Johnson, Jay S; Horst, Erin A; Rhoads, Robert P; Baumgard, Lance H

    2015-01-01

    Proper insulin homeostasis appears critical for adapting to and surviving a heat load. Further, heat stress (HS) induces phenotypic changes in livestock that suggest an increase in insulin action. The current study objective was to evaluate the effects of HS on whole-body insulin sensitivity. Female pigs (57 ± 4 kg body weight) were subjected to two experimental periods. During period 1, all pigs remained in thermoneutral conditions (TN; 21°C) and were fed ad libitum. During period 2, pigs were exposed to: (i) constant HS conditions (32°C) and fed ad libitum (n = 6), or (ii) TN conditions and pair-fed (PFTN; n = 6) to eliminate the confounding effects of dissimilar feed intake. A hyperinsulinemic euglycemic clamp (HEC) was conducted on d3 of both periods; and skeletal muscle and adipose tissue biopsies were collected prior to and after an insulin tolerance test (ITT) on d5 of period 2. During the HEC, insulin infusion increased circulating insulin and decreased plasma C-peptide and nonesterified fatty acids, similarly between treatments. From period 1 to 2, the rate of glucose infusion in response to the HEC remained similar in HS pigs while it decreased (36%) in PFTN controls. Prior to the ITT, HS increased (41%) skeletal muscle insulin receptor substrate-1 protein abundance, but did not affect protein kinase B or their phosphorylated forms. In adipose tissue, HS did not alter any of the basal or stimulated measured insulin signaling markers. In summary, HS increases whole-body insulin-stimulated glucose uptake. PMID:26243213

  3. D-(U-11C)glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects

    SciTech Connect

    Gutniak, M.; Blomqvist, G.; Widen, L.; Stone-Elander, S.; Hamberger, B.; Grill, V. )

    1990-05-01

    We used D-(U-11C)glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-(U-11C)-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia (arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects). Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects.

  4. Personalized State-space Modeling of Glucose Dynamics for Type 1 Diabetes Using Continuously Monitored Glucose, Insulin Dose, and Meal Intake

    PubMed Central

    Molenaar, Peter; Harsh, Saurabh; Freeman, Kenneth; Xie, Jinyu; Gold, Carol; Rovine, Mike; Ulbrecht, Jan

    2014-01-01

    An essential component of any artificial pancreas is on the prediction of blood glucose levels as a function of exogenous and endogenous perturbations such as insulin dose, meal intake, and physical activity and emotional tone under natural living conditions. In this article, we present a new data-driven state-space dynamic model with time-varying coefficients that are used to explicitly quantify the time-varying patient-specific effects of insulin dose and meal intake on blood glucose fluctuations. Using the 3-variate time series of glucose level, insulin dose, and meal intake of an individual type 1 diabetic subject, we apply an extended Kalman filter (EKF) to estimate time-varying coefficients of the patient-specific state-space model. We evaluate our empirical modeling using (1) the FDA-approved UVa/Padova simulator with 30 virtual patients and (2) clinical data of 5 type 1 diabetic patients under natural living conditions. Compared to a forgetting-factor-based recursive ARX model of the same order, the EKF model predictions have higher fit, and significantly better temporal gain and J index and thus are superior in early detection of upward and downward trends in glucose. The EKF based state-space model developed in this article is particularly suitable for model-based state-feedback control designs since the Kalman filter estimates the state variable of the glucose dynamics based on the measured glucose time series. In addition, since the model parameters are estimated in real time, this model is also suitable for adaptive control. PMID:24876585

  5. Personalized State-space Modeling of Glucose Dynamics for Type 1 Diabetes Using Continuously Monitored Glucose, Insulin Dose, and Meal Intake: An Extended Kalman Filter Approach.

    PubMed

    Wang, Qian; Molenaar, Peter; Harsh, Saurabh; Freeman, Kenneth; Xie, Jinyu; Gold, Carol; Rovine, Mike; Ulbrecht, Jan

    2014-03-24

    An essential component of any artificial pancreas is on the prediction of blood glucose levels as a function of exogenous and endogenous perturbations such as insulin dose, meal intake, and physical activity and emotional tone under natural living conditions. In this article, we present a new data-driven state-space dynamic model with time-varying coefficients that are used to explicitly quantify the time-varying patient-specific effects of insulin dose and meal intake on blood glucose fluctuations. Using the 3-variate time series of glucose level, insulin dose, and meal intake of an individual type 1 diabetic subject, we apply an extended Kalman filter (EKF) to estimate time-varying coefficients of the patient-specific state-space model. We evaluate our empirical modeling using (1) the FDA-approved UVa/Padova simulator with 30 virtual patients and (2) clinical data of 5 type 1 diabetic patients under natural living conditions. Compared to a forgetting-factor-based recursive ARX model of the same order, the EKF model predictions have higher fit, and significantly better temporal gain and J index and thus are superior in early detection of upward and downward trends in glucose. The EKF based state-space model developed in this article is particularly suitable for model-based state-feedback control designs since the Kalman filter estimates the state variable of the glucose dynamics based on the measured glucose time series. In addition, since the model parameters are estimated in real time, this model is also suitable for adaptive control. PMID:24876585

  6. Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt–mTOR–S6K1 pathway and insulin sensitivity

    PubMed Central

    Gingras, Andrée-Anne; White, Phillip James; Chouinard, P Yvan; Julien, Pierre; Davis, Teresa A; Dombrowski, Luce; Couture, Yvon; Dubreuil, Pascal; Myre, Alexandre; Bergeron, Karen; Marette, André; Thivierge, M Carole

    2007-01-01

    The ability of the skeletal musculature to use amino acids to build or renew constitutive proteins is gradually lost with age and this is partly due to a decline in skeletal muscle insulin sensitivity. Since long-chain omega-3 polyunsaturated fatty acids (LCn–3PUFA) from fish oil are known to improve insulin-mediated glucose metabolism in insulin-resistant states, their potential role in regulating insulin-mediated protein metabolism was investigated in this study. Experimental data are based on a switchback design composed of three 5 week experimental periods using six growing steers to compare the effect of a continuous abomasal infusion of LCn–3PUFA-rich menhaden oil with an iso-energetic control oil mixture. Clamp and insulin signalling observations were combined with additional data from a second cohort of six steers. We found that enteral LCn–3PUFA potentiate insulin action by increasing the insulin-stimulated whole-body disposal of amino acids from 152 to 308 μmol kg−1 h−1 (P = 0.006). The study further showed that in the fed steady-state, chronic adaptation to LCn–3PUFA induces greater activation (P < 0.05) of the Akt–mTOR–S6K1 signalling pathway. Simultaneously, whole-body total flux of phenylalanine was reduced from 87 to 67 μmol kg−1 h−1 (P = 0.04) and oxidative metabolism was decreased (P = 0.05). We conclude that chronic feeding of menhaden oil provides a novel nutritional mean to enhance insulin-sensitive aspects of protein metabolism. PMID:17158167

  7. Long-chain omega-3 fatty acids regulate bovine whole-body protein metabolism by promoting muscle insulin signalling to the Akt-mTOR-S6K1 pathway and insulin sensitivity.

    PubMed

    Gingras, Andrée-Anne; White, Phillip James; Chouinard, P Yvan; Julien, Pierre; Davis, Teresa A; Dombrowski, Luce; Couture, Yvon; Dubreuil, Pascal; Myre, Alexandre; Bergeron, Karen; Marette, André; Thivierge, M Carole

    2007-02-15

    The ability of the skeletal musculature to use amino acids to build or renew constitutive proteins is gradually lost with age and this is partly due to a decline in skeletal muscle insulin sensitivity. Since long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) from fish oil are known to improve insulin-mediated glucose metabolism in insulin-resistant states, their potential role in regulating insulin-mediated protein metabolism was investigated in this study. Experimental data are based on a switchback design composed of three 5 week experimental periods using six growing steers to compare the effect of a continuous abomasal infusion of LCn-3PUFA-rich menhaden oil with an iso-energetic control oil mixture. Clamp and insulin signalling observations were combined with additional data from a second cohort of six steers. We found that enteral LCn-3PUFA potentiate insulin action by increasing the insulin-stimulated whole-body disposal of amino acids from 152 to 308 micromol kg(-1) h(-1) (P=0.006). The study further showed that in the fed steady-state, chronic adaptation to LCn-3PUFA induces greater activation (P<0.05) of the Akt-mTOR-S6K1 signalling pathway. Simultaneously, whole-body total flux of phenylalanine was reduced from 87 to 67 micromol kg(-1) h(-1) (P=0.04) and oxidative metabolism was decreased (P=0.05). We conclude that chronic feeding of menhaden oil provides a novel nutritional mean to enhance insulin-sensitive aspects of protein metabolism. PMID:17158167

  8. Dietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans

    PubMed Central

    Byrne, Loretta M.; Yu, Chang; Wang, Thomas J.; Brown, Nancy J.

    2014-01-01

    Context: Interruption of the renin-angiotensin-aldosterone system prevents incident diabetes in high-risk individuals, although the mechanism remains unclear. Objective: To test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system or exogenous aldosterone impairs insulin secretion in humans. Design: We conducted a randomized, blinded crossover study of aldosterone vs vehicle and compared the effects of a low-sodium versus a high-sodium diet. Setting: Academic clinical research center. Participants: Healthy, nondiabetic, normotensive volunteers. Interventions: Infusion of exogenous aldosterone (0.7 μg/kg/h for 12.5 h) or vehicle during low or high sodium intake. Low sodium (20 mmol/d; n = 12) vs high sodium (160 mmol/d; n = 17) intake for 5–7 days. Main Outcome Measures: Change in acute insulin secretory response assessed during hyperglycemic clamps while in sodium balance during a low-sodium vs high-sodium diet during aldosterone vs vehicle. Results: A low-sodium diet increased endogenous aldosterone and plasma renin activity, and acute glucose-stimulated insulin (−16.0 ± 5.6%; P = .007) and C-peptide responses (−21.8 ± 8.4%; P = .014) were decreased, whereas the insulin sensitivity index was unchanged (−1.0 ± 10.7%; P = .98). Aldosterone infusion did not affect the acute insulin response (+1.8 ± 4.8%; P = .72) or insulin sensitivity index (+2.0 ± 8.8%; P = .78). Systolic blood pressure and serum potassium were similar during low and high sodium intake and during aldosterone infusion. Conclusions: Low dietary sodium intake reduces insulin secretion in humans, independent of insulin sensitivity. PMID:25029426

  9. Effects of High-Intensity Interval Exercise versus Moderate Continuous Exercise on Glucose Homeostasis and Hormone Response in Patients with Type 1 Diabetes Mellitus Using Novel Ultra-Long-Acting Insulin

    PubMed Central

    Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R.; Obermayer-Pietsch, Barbara; Koehler, Gerd; Hofmann, Peter

    2015-01-01

    Introduction We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM). Material and Methods Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system. Results BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C. Conclusion Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM. Trial Registration ClinicalTrials.gov NCT02075567 http

  10. Robust liquid-infused surfaces through patterned wettability

    NASA Astrophysics Data System (ADS)

    Wexer, Jason; Grosskopf, Abigail; Chow, Melissa; Fan, Yuyang; Jacobi, Ian; Stone, Howard

    2015-11-01

    Liquid-infused surfaces display advantageous properties that are normally associated with conventional gas-cushioned superhydrophobic surfaces. However, the surfaces can lose their novel properties if the infused liquid drains from the surface. We explore how drainage due to gravity or due to an external flow can be prevented through the use of chemical patterning. A small area of the overall surface is chemically treated to be preferentially wetted by the external fluid rather than the infused liquid. These sacrificial regions disrupt the continuity of the infused liquid, thereby preventing the liquid from draining from the texture. If the regions are patterned with the correct periodicity, drainage can be prevented entirely. The chemical patterns are created using spray-coating or deep-UV exposure, two economical techniques that are scalable to generate large-scale failure-resistant surfaces.

  11. Robust liquid-infused surfaces through patterned wettability.

    PubMed

    Wexler, Jason S; Grosskopf, Abigail; Chow, Melissa; Fan, Yuyang; Jacobi, Ian; Stone, Howard A

    2015-07-01

    Liquid-infused surfaces display advantageous properties that are normally associated with conventional gas-cushioned superhydrophobic surfaces. However, the surfaces can lose their novel properties if the infused liquid drains from the surface. We explore how drainage due to gravity or due to an external flow can be prevented through the use of chemical patterning. A small area of the overall surface is chemically treated to be preferentially wetted by the external fluid rather than the infused liquid. These sacrificial regions disrupt the continuity of the infused liquid, thereby preventing the liquid from draining from the texture. If the regions are patterned with the correct periodicity, drainage can be prevented entirely. The chemical patterns are created using spray-coating or deep-UV exposure, two facile techniques that are scalable to generate large-scale failure-resistant surfaces. PMID:26014378

  12. Features of Hepatic and Skeletal Muscle Insulin Resistance Unique to Type 1 Diabetes

    PubMed Central

    Howard, David; Schauer, Irene E.; Maahs, David M.; Snell-Bergeon, Janet K.; Eckel, Robert H.; Perreault, Leigh; Rewers, Marian

    2012-01-01

    Context: Type 1 diabetes is known to be a state of insulin resistance; however, the tissues involved in whole-body insulin resistance are less well known. It is unclear whether insulin resistance is due to glucose toxicity in the post-Diabetes Control and Complications Trial era of tighter glucose control. Objective: We performed this study to determine muscle and liver insulin sensitivity individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose concentration. Design, Patients, and Methods: Fifty subjects [25 controls without and 25 individuals with type 1 diabetes (diabetes duration 22.9 ± 1.7 yr, without known end organ damage] were frequency matched on age and body mass index by group and studied. After 3 d of dietary control and overnight insulin infusion to normalize glucose, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m2 · min. Glucose metabolism was quantified using an infusion of [6,6-2H2]glucose. Hepatic insulin sensitivity was measured using the insulin IC50 for glucose rate of appearance (Ra), whereas muscle insulin sensitivity was measured using the glucose rate of disappearance during the highest insulin dose. Results: Throughout the study, glucose Ra was significantly greater in individuals compared with those without type 1 diabetes. The concentration of insulin required for 50% suppression of glucose Ra was 2-fold higher in subjects with type 1 diabetes. Glucose rate of disappearance was significantly lower in individuals with type 1 diabetes during the 8- and 40-mU/m2 · min stages. Conclusion: Insulin resistance in liver and skeletal muscle was a significant feature in type 1 diabetes. Nevertheless, the etiology of insulin resistance was not explained by body mass index, percentage fat, plasma lipids, visceral fat, and physical activity and was also not fully explained by hyperglycemia. PMID:22362823

  13. Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus.

    PubMed Central

    Ehrmann, D A; Sturis, J; Byrne, M M; Karrison, T; Rosenfield, R L; Polonsky, K S

    1995-01-01

    The increased prevalence of non-insulin-dependent diabetes mellitus (NIDDM) among women with polycystic ovary syndrome (PCOS) has been ascribed to the insulin resistance characteristic of PCOS. This study was undertaken to determine the role of defects in insulin secretion as well as familial factors to the predisposition to NIDDM seen in PCOS. We studied three groups of women: PCOS with a family history of NIDDM (PCOS FHx POS; n = 11), PCOS without a family history of NIDDM (PCOS FHx NEG; n = 13), and women without PCOS who have a family history of NIDDM (NON-PCOS FHx POS; n = 8). Beta cell function was evaluated during a frequently sampled intravenous glucose tolerance test, by a low dose graded glucose infusion, and by the ability of the beta cell to be entrained by an oscillatory glucose infusion. PCOS FHx POS women were significantly less likely to demonstrate appropriate beta cell compensation for the degree of insulin resistance. The ability of the beta cell to entrain, as judged by the spectral power for insulin secretion rate, was significantly reduced in PCOS FHx POS subjects. In conclusion, a history of NIDDM in a first-degree relative appears to define a subset of PCOS subjects with a greater prevalence of insulin secretory defects. The risk of developing NIDDM imparted by insulin resistance in PCOS may be enhanced by these defects in insulin secretion. PMID:7615824

  14. Responses to Starch Infusion on Milk Synthesis in Low Yield Lactating Dairy Cows

    PubMed Central

    Zou, Yang; Yang, Zhanshan; Guo, Yongqing; Li, Shengli; Cao, Zhijun

    2015-01-01

    The effect of starch infusion on production, metabolic parameters and relative mRNA abundance was investigated in low yield lactating cows from 86 days in milk. Six Holstein cows fitted with permanent ruminal cannulas were arranged into one of two complete 3×3 Latin squares and infused with a starch solution containing 800 grams starch for 16 days. The three treatments were: i) ruminal and abomasal infusion with water (Control); ii) ruminal infusion with cornstarch solution and abomasal infusion with water (Rumen); iii) ruminal infusion with water and abomasal infusion with cornstarch solution (Abomasum). There were no significant differences (p>0.05) among the three treatments with low yield lactating cows in feed and energy intake, milk yield and composition, plasma metabolism, or even on gene expression. However, cows receiving starch through rumen performed better than directly through the abomasum during the glucose tolerance test procedure with a higher area under the curve (AUC; p = 0.08) and shorter half-time (t1/2; p = 0.11) of plasma insulin, therefore, it increased glucose disposal, which stated a lipid anabolism other than mobilization after energy supplementation. In conclusion, extra starch infusion at concentration of 800 g/d did not enhance energy supplies to the mammary gland and improve the lactating performance in low yield lactating cows. PMID:26194224

  15. The influence of gastrointestinal infusion of fats on regulation of food intake in pigs.

    PubMed Central

    Gregory, P C; Rayner, D V

    1987-01-01

    1. The influence of gastrointestinal infusions of fat on short-term and 24 h control of food intake were studied in twenty-four pigs fed twice per day and seventeen fed three times per day. The pigs were fitted with up to four catheters placed in the stomach, the duodenum, and at 2, 4 and 8 m from the ligament of Treitz. 2. Various infusions were given into the catheters beginning 30 min before the first meal (two feeds) or second meal (three feeds) of the day and continuing until the end of the feeding period or until the pigs stopped eating. 3. Infusions of a fat emulsion (Intralipid) into the stomach, of oleic acid or glycerol into the duodenum, or of glycerol into the ileum (8 m from the ligament of Treitz) inhibited food intake during the infusion according to the amount of energy infused. 4. Food intake was inhibited by more than the amount of energy infused with duodenal infusion of Intralipid or monoglyceride, or with infusion of Intralipid mixed with bile salts and lipase (but not with Intralipid alone) into 2 or 4 m from the ligament of Treitz. 5. Duodenal infusion of glycerol, and ileal (8 m from the ligament of Treitz) infusion of monoglyceride or glycerol inhibited food intake at the following meal according to the amount of energy infused. 6. It is concluded that fats can exert both pre- and post-absorptive control of food intake and that since Intralipid infusion to the stomach but not to the duodenum inhibits food intake according to the amount of energy infused, it is likely that control of food intake is related to control of stomach emptying. 7. The inhibition of food intake by more than the amount of energy infused during upper intestinal infusion of fat is likely to be a result of digestion of the fat to monoglycerides, and interaction of monoglycerides with receptors in the proximal 4 m of intestine. PMID:3656166

  16. Leptin, skeletal muscle lipids, and lipid-induced insulin resistance.

    PubMed

    Dube, John J; Bhatt, Bankim A; Dedousis, Nikolas; Bonen, Arend; O'Doherty, Robert M

    2007-08-01

    Leptin-induced increases in insulin sensitivity are well established and may be related to the effects of leptin on lipid metabolism. However, the effects of leptin on the levels of lipid metabolites implicated in pathogenesis of insulin resistance and the effects of leptin on lipid-induced insulin resistance are unknown. The current study addressed in rats the effects of hyperleptinemia (HL) on insulin action and markers of skeletal muscle (SkM) lipid metabolism in the absence or presence of acute hyperlipidemia induced by an infusion of a lipid emulsion. Compared with controls (CONT), HL increased insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamp ( approximately 15%), and increased SkM Akt ( approximately 30%) and glycogen synthase kinase 3 alpha ( approximately 52%) phosphorylation. These improvements in insulin action were associated with decreased SkM triglycerides (TG; approximately 61%), elevated ceramides ( approximately 50%), and similar diacylglycerol (DAG) levels in HL compared with CONT. Acute hyperlipidemia in CONT decreased insulin sensitivity ( approximately 25%) and increased SkM DAG ( approximately 33%) and ceramide ( approximately 60%) levels. However, hyperlipidemia did not induce insulin resistance or SkM DAG and ceramide accumulation in HL. SkM total fatty acid transporter CD36, plasma membrane fatty acid binding protein, acetyl Co-A carboxylase phosphorylation, and fatty acid oxidation were similar in HL compared with CONT. However, HL decreased SkM protein kinase C theta (PKC theta), a kinase implicated in mediating the detrimental effects of lipids on insulin action. We conclude that increases in insulin sensitivity induced by HL are associated with decreased levels of SkM TG and PKC theta and increased SkM insulin signaling, but not with decreases in other lipid metabolites implicated in altering SkM insulin sensitivity (DAG and ceramide). Furthermore, insulin resistance induced by an acute lipid infusion is prevented by

  17. Insulin transport across capillaries is rate limiting for insulin action in dogs.

    PubMed Central

    Yang, Y J; Hope, I D; Ader, M; Bergman, R N

    1989-01-01

    This study examined the relationship between transcapillary insulin transport and insulin action in vivo. During euglycemic clamps (n = 7) in normal conscious dogs we simultaneously measured plasma and thoracic duct lymph insulin and glucose utilization (Rd). Clamps consisted of an activation phase with constant insulin infusion (0.6 mU/kg per min) and a deactivation phase. [14C]Inulin was infused as a passively transported control substance. While [14C]inulin reached an equilibrium between plasma and lymph, steady-state (ss) plasma insulin was higher than lymph (P less than 0.05) and the ratio of 3:2 was maintained during basal, activation, and deactivation phases: 18 +/- 2 vs. 12 +/- 1, 51 +/- 2 vs. 32 +/- 1, and 18 +/- 3 vs. 13 +/- 1 microU/ml. In addition, it took longer for lymph insulin to reach ss than plasma insulin during activation and deactivation: 11 +/- 2 vs. 31 +/- 5 and 8 +/- 2 vs. 32 +/- 6 min (P less than 0.02). Rd increased from 2.6 +/- 0.1 to a ss of 6.6 +/- 0.4 mg/kg per min within 50 +/- 8 min. There was a remarkable similarity in the dynamics of insulin in lymph and Rd: the time to reach ss for Rd was not different from lymph insulin (P greater than 0.1), and the relative increases of the two measurements were similar, 164 +/- 45% and 189 +/- 29% (P greater than 0.05). While there was only a modest correlation (r = 0.78, P less than 0.01) between Rd and plasma insulin, the dynamic changes of lymph insulin and Rd showed a strong correlation (r = 0.95, P less than 0.01). The intimate relationship between lymph insulin and Rd suggests that the transcapillary insulin transport is primarily responsible for the delay in Rd. Thus, transcapillary transport may be rate limiting for insulin action, and if altered, it could be an important component of insulin resistance in obesity and diabetes mellitus. PMID:2681272

  18. Adenosine enhances myocardial glucose uptake only in the presence of insulin.

    PubMed

    Law, W R; McLane, M P

    1991-09-01

    Better understood in other tissues, the effects of adenosine on insulin-stimulated glucose uptake in the heart are poorly understood. Under pentobarbital anesthesia, we instrumented mongrel dogs to obtain general hemodynamics (blood pressure and heart rate), and arterial and coronary sinus blood samples for measuring oxygen and glucose concentrations. An electromagnetic blood flow probe around the circumflex coronary artery allowed determinations of blood flow, and calculation of substrate uptake by the heart (Fick principle). Somatostatin (SRIF) was infused intravenously (0.8 micrograms/kg/min) along with 0, 0.5, 1.0, 5.0, or 10 mU/kg/min regular insulin, and variable quantities of glucose to maintain euglycemia. Concomitant with the SRIF, insulin, and glucose infusions, adenosine was infused in logarithmically increasing rates (0, 0.01, 0.1, 1.0, 10 or 100 mumol/min) for 30 minutes each into the main left coronary arteries. Insulin infusions increased myocardial glucose uptake in a dose-dependent manner. The heart displayed exquisite sensitivity to insulin, with an ED50 of approximately 14 microU/mL (serum insulin). Adenosine infusions in the absence of insulin (SRIF infusion) increased coronary blood flow, but did not alter myocardial glucose uptake. In the presence of insulin, adenosine increased the maximal value for glucose uptake without changing sensitivity to insulin. These results indicate that adenosine enhances myocardial responsiveness to insulin, with respect to glucose uptake, independent of changes in blood flow. Since glucose can be used for anaerobic metabolism, and adenosine levels are known to increase under situations in which myocardial oxygenation is inadequate, these data have serious implications for conditions such as myocardial ischemia or hypoxia, when glycolytic substrate availability is vital. PMID:1680214

  19. Insulin improves memory and reduces chronic neuroinflammation in the hippocampus of young but not aged brains.

    PubMed

    Adzovic, Linda; Lynn, Ashley E; D'Angelo, Heather M; Crockett, Alexis M; Kaercher, Roxanne M; Royer, Sarah E; Hopp, Sarah C; Wenk, Gary L

    2015-01-01

    The role of insulin in the brain is still not completely understood. In the periphery, insulin can decrease inflammation induced by lipopolysaccharide (LPS); however, whether insulin can reduce inflammation within the brain is unknown. Experiments administrating intranasal insulin to young and aged adults have shown that insulin improves memory. In our animal model of chronic neuroinflammation, we administered insulin and/or LPS directly into the brain via the fourth ventricle for 4 weeks in young rats; we then analyzed their spatial memory and neuroinflammatory response. Additionally, we administered insulin or artificial cerebral spinal fluid (aCSF), in the same manner, to aged rats and then analyzed their spatial memory and neuroinflammatory response. Response to chronic neuroinflammation in young rats was analyzed in the presence or absence of insulin supplementation. Here, we show for the first time that insulin infused (i.c.v.) to young rats significantly attenuated the effects of LPS by decreasing the expression of neuroinflammatory markers in the hippocampus and by improving performance in the Morris water pool task. In young rats, insulin infusion alone significantly improved their performance as compared to all other groups. Unexpectedly, in aged rats, the responsiveness to insulin was completely absent, that is, spatial memory was still impaired suggesting that an age-dependent insulin resistance may contribute to the cognitive impairment observed in neurodegenerative diseases. Our data suggest a novel therapeutic effect of insulin on neuroinflammation in the young but not the aged brain. PMID:25889938

  20. Intraosseous infusion in pediatric patients.

    PubMed

    Neal, C J; McKinley, D F

    1994-01-01

    In traumatically injured or medically unstable pediatric patients requiring resuscitation, gaining intravenous access often is frustrating for the physician and agonizing for the patient. Even when cardiopulmonary resuscitation is performed by trained professionals, cardiac arrests in children in the prehospital setting have a mortality of 79% to 100%. Immediate vascular access such as that obtained by intraosseous infusion improves survival. The intraosseous infusion technique uses the medullary cavity in the tibia as a "noncollapsible vein" for parenteral infusion. It is indicated in a child in shock or cardiac arrest when two attempts to access peripheral vasculature have failed or when more than 2 minutes have elapsed in the attempt to gain access. Epinephrine, bicarbonate, calcium, lidocaine, and volume expanders can be infused via the intraosseous route. Complications rarely occur. The technique described here is gaining acceptance in both prehospital and emergency department settings. PMID:8169160

  1. Proctoclysis: emergency rectal fluid infusion.

    PubMed

    Tremayne, Vincent

    This article describes the use and effectiveness of proctoclysis (rectal fluid infusion) in providing fluid resuscitation in the absence of intravenous access in rural and remote environments. PMID:19856644

  2. Diabetes and Insulin

    MedlinePlus

    ... years, but may eventually need insulin to maintain glucose control. What are the different types of insulin? Different ... glulisine • Short-acting: regular human insulin Basal insulin. Controls blood glucose levels between meals and throughout the night. This ...

  3. Changes in Postpartum Insulin Requirements for Patients with Well-Controlled Type 1 Diabetes.

    PubMed

    Roeder, Hilary A; Moore, Thomas R; Ramos, Gladys A

    2016-06-01

    Objective To compare postpartum with preconception insulin doses in well-controlled (HbA1c ≤ 7.4%) type 1 diabetes mellitus (T1DM) and to characterize differences in postpartum insulin dosing based on infant feeding. Study Design The primary outcome in this retrospective cohort was the change in total daily insulin (TDI) from preconception to postpartum. Insulin administration (continuous subcutaneous insulin infusion [CSII] vs. multiple daily injections [MDI]), HbA1c, body mass index (BMI), and infant feeding were abstracted. Results We identified 44 women with T1DM and HbA1c ≤ 7.4%. Preconception mean BMI was 24.6 ± 3.6 kg/m(2) and median (interquartile range [IQR]) HbA1c was 6.4 (6.0-6.9)%. Of these, 73% used CSII and 27% used MDI. Additionally, 80% of patients reported exclusive breastfeeding, 7% were exclusively formula feeding, and 13% used both breast milk and formula. Median (IQR) preconception TDI was 0.64 (0.49-0.69) U/kg/day, and postpartum: 0.39 (0.30-0.50) U/kg/day. Postpartum TDI was 34% lower than preconception TDI (p = 0.02). There was no difference in the postpartum TDI in patients who were breast versus formula feeding or when comparing CSII with MDI. Conclusion There was a significant decrease in the TDI required postpartum when compared with preconception. Dosages do not seem to be impacted by administration route or breastfeeding. These findings warrant consideration when dosing postpartum insulin in patients with T1DM. PMID:26862721

  4. Insulin Pump and CGM Usage in the United States and Germany

    PubMed Central

    Walsh, John; Roberts, Ruth; Weber, Dietmar; Faber-Heinemann, Gabriele; Heinemann, Lutz

    2015-01-01

    Background: This survey collected and evaluated user responses about routine tasks and preferences regarding insulin pumps and infusion sets (IIS) with comparison of intercountry differences between the United States (US) and Germany (GER), chosen for their large insulin pump populations. Methods: A total of 985 subjects (534 US, 451 GER; 60% female) with type 1 diabetes on pump therapy anonymously answered 20 pump-related questions. US subjects also answered 11 questions about continuous glucose monitoring (CGM) usage. Results: Length of use of insulin cartridges is shorter in US than in GER, mean (SD) 4.3 (5.0) versus 5.3 (3.2) days (P < .001), while the IIS is used longer: 3.3 (1.0) versus 2.7 (1.1) days (P < .001). Lower self-reported HbA1c levels were associated with longer use of insulin cartridges (7.3% for >3 days vs 7.7% for <3 days; P < .01), and with use of an auto-insertion device (vs manual IIS insertion) in the US (7.2% vs 6.9%), but not in GER (7.7% vs 7.9%). Only 47% of pump wearers stated that they were “very satisfied” with their pump (49% US vs 45% GER, ns). However, 98% would recommend the pump to others (95% vs 93%, ns). Analysis of CGM questions showed that 297 (60%) of 496 US responders currently wore one. Of these, 84% said they would recommend CGM to others. CGM wearers who stated they were “very satisfied” with their CGM had lower HbA1c than those who said they were “partly satisfied” (6.9% vs 7.2%). Conclusions: This survey shows interesting differences in real-world use of insulin pumps in 2 large markets, and suggests areas where insulin pumps and CGMs might be improved. PMID:26071425

  5. [Transitory hyperbilirubinemia and oxytocin infusion].

    PubMed

    Quoss, I

    1978-01-01

    Serum bilirubin levels at 5th day of life was compared between 100 mature newborns with oxytocin infusion to the mother during labour and 100 mature newborns without oxytocin. Newborns, whose mothers received more than 5 IU oxytocin had significant higher bilirubin values than the controll group without oxytocin and the cases with oxytocin administration under 5 U. Hyperbilirubinaemie was also present in babies after vacuum extraction and oxytocin infusion. PMID:645287

  6. Metabolic clearance of insulin from the cerebrospinal fluid in the anesthetized rat

    SciTech Connect

    Manin, M.; Broer, Y.; Balage, M.; Rostene, W.; Grizard, J. )

    1990-01-01

    Infusion of 125I-(Tyr A14)-insulin at tracer doses into the cerebrospinal fluid (CSF) resulted in a slow rate of increase in the CSF-labeled insulin during the first 2 hours with a plateau thereafter. Labeled insulin was cleared from the CSF at a higher rate than 3H-inulin, a marker of CSF bulk flow. The labeled insulin was mainly distributed in all the ventricular and periventricular brain regions. Small amounts of degraded insulin appeared in the CSF. Coinfusion with an excess of unlabeled insulin impaired the clearance and degradation of labeled insulin. It also inhibited the labeling in medial hypothalamus, olfactory bulbs and brain stem. In contrast, coinfusion of ribonuclease B (used to test the specificity of uptake) was without any effect. It was concluded that there is an active insulin intake from CSF into brain specific compartments that is presumably essential for the effects of insulin on brain function.

  7. Intravenous labetolol in treating hypertensive crisis following dexmedetomidine infusion for procedural sedation.

    PubMed

    Muthiah, Thilaka; Moni, Amarnath; Mathews, Lailu; Balaji, Sudarshan

    2016-03-01

    Dexmedetomidine is widely used for procedural sedation because of its unique combination of sedation, analgesia, and anxiolysis with minimal respiratory depression. Transient hypertension has been reported during the use of dexmedetomidine which is usually benign and is taken over by the hypotensive response on continuing the infusion. We report a case of hypertensive crisis following dexmedetomidine infusion used for procedural sedation, necessitating discontinuation of the infusion and treatment of hypertension. The dilemmas involved in treating hypertension caused by dexmedetomidine are discussed. PMID:26897444

  8. Decrease in glucose-stimulated insulin secretion with aging is independent of insulin action.

    PubMed

    Muzumdar, Radhika; Ma, Xiaohui; Atzmon, Gil; Vuguin, Patricia; Yang, Xiaoman; Barzilai, Nir

    2004-02-01

    While the incidence of diabetes increases with age, a decrease in beta-cell function independent of age-related insulin resistance has not been conclusively determined. We studied insulin secretion (by hyperglycemic clamp) in 3-, 9-, and 20-month-old chronically catheterized, awake, Sprague Dawley (SD) rats (n = 78). Insulin action was modulated in a group of old rats by caloric restriction (CR) or by surgical removal of visceral fat (VF-). During the first 2 h of the clamp (11 mmol/l glucose), insulin secretion and insulin resistance (S(i hyper clamp)) demonstrated the characteristic hyperbolic relationship. However, after hyperglycemia for an additional 2 h, the ability to maintain insulin secretion, commensurate with the degree of insulin resistance, was decreased in all aging rats (P < 0.05). Increasing plasma glucose levels to 18 mmol/l glucose, after clamp at 11 mmol/l, increased insulin secretion by approximately threefold in young rats, but failed to induce similar magnitude of response in the aging rats ( approximately 50%). However, elevation of plasma free fatty acid (FFA) levels by twofold (by intralipid infusion during 11 mmol/l glucose clamp) resulted in a robust, approximate twofold response in both young and old rats. Thus, prolonged stimulation by hyperglycemia unveiled a functional defect in insulin secretion with aging. This age-related defect is independent of insulin action and is specific to glucose and not FFAs. We suggest that prolonged hyperglycemic stimulation can be a tool to identify functional defects in insulin secretion, particularly in the context of the hyperbolic relationship with insulin action, in elderly subjects or those at risk for type 2 diabetes. PMID:14747296

  9. Insulin stimulates muscle protein synthesis in neonates during endotoxemia despite repression of translation initiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Skeletal muscle protein synthesis is reduced in neonatal pigs in response to endotoxemia. To examine the role of insulin in this response, neonatal pigs were infused with endotoxin (LPS, 0 and 10 µg•kg(-1)•h(-1)), whereas glucose and amino acids were maintained at fasting levels and insulin was clam...

  10. Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice.

    PubMed

    Musial, Barbara; Fernandez-Twinn, Denise S; Vaughan, Owen R; Ozanne, Susan E; Voshol, Peter; Sferruzzi-Perri, Amanda N; Fowden, Abigail L

    2016-04-01

    In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling protein abundance by Western blotting, glucose tolerance and utilization, and insulin sensitivity using acute insulin administration and hyperinsulinemic-euglycemic clamps with [(3)H]glucose infusion. Whole-body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinemia, insulin-resistant endogenous glucose production, and downregulation of several proteins in hepatic and skeletal muscle insulin signaling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19, with restoration of NP insulin concentrations, improved hepatic insulin sensitivity, and increased abundance of hepatic insulin signaling proteins. At D16, insulin resistance at whole-body, tissue, and molecular levels will favor fetal glucose acquisition, while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice, with implications for human and other species. PMID:26740602

  11. PROXIMITY TO DELIVERY ALTERS INSULIN SENSITIVITY AND GLUCOSE METABOLISM IN PREGNANT MICE

    PubMed Central

    Musial, Barbara; Fernandez-Twinn, Denise S.; Vaughan, Owen R.; Ozanne, Susan E.; Voshol, Peter; Sferruzzi-Perri, Amanda N.; Fowden, Abigail L.

    2016-01-01

    In late pregnancy, maternal insulin resistance occurs to support fetal growth but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy, day (D) 16, and near term, D19, (term 20.5D). Non-pregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by dual energy X-ray absorptiometry, tissue insulin signalling protein abundance by Western blotting, glucose tolerance and utilisation, and insulin sensitivity using acute insulin administration and hyperinsulinaemic-euglycaemic clamps with 3H-glucose infusion. Whole body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinaemia, insulin-resistant endogenous glucose production and downregulation of several proteins in hepatic and skeletal muscle insulin signalling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19 with restoration of NP insulin concentrations, improved hepatic insulin sensitivity and increased abundance of hepatic insulin signalling proteins. At D16, insulin resistance at whole body, tissue and molecular levels will favour fetal glucose acquisition while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice with implications for human and other species. PMID:26740602

  12. Insulin sensitivity of muscle protein metabolism is altered in patients with chronic kidney disease and metabolic acidosis

    PubMed Central

    Garibotto, Giacomo; Sofia, Antonella; Russo, Rodolfo; Paoletti, Ernesto; Bonanni, Alice; Parodi, Emanuele L; Viazzi, Francesca; Verzola, Daniela

    2015-01-01

    An emergent hypothesis is that a resistance to the anabolic drive by insulin may contribute to loss of strength and muscle mass in patients with chronic kidney disease (CKD). We tested whether insulin resistance extends to protein metabolism using the forearm perfusion method with arterial insulin infusion in 7 patients with CKD and metabolic acidosis (bicarbonate 19 mmol/l) and 7 control individuals. Forearm glucose balance and protein turnover (2H-phenylalanine kinetics) were measured basally and in response to insulin infused at different rates for 2 h to increase local forearm plasma insulin concentration by approximately 20 and 50 μU/ml. In response to insulin, forearm glucose uptake was significantly increased to a lesser extent (−40%) in patients with CKD than controls. In addition, whereas in the controls net muscle protein balance and protein degradation were decreased by both insulin infusion rates, in patients with CKD net protein balance and protein degradation were sensitive to the high (0.035 mU/kg per min) but not the low (0.01 mU/kg per min) insulin infusion. Besides blunting muscle glucose uptake, CKD and acidosis interfere with the normal suppression of protein degradation in response to a moderate rise in plasma insulin. Thus, alteration of protein metabolism by insulin may lead to changes in body tissue composition which may become clinically evident in conditions characterized by low insulinemia. PMID:26308671

  13. Interactions of glucagon and free fatty acids with insulin in control of glucose metabolism

    SciTech Connect

    Chambrier, C.; Picard, S.; Vidal, H.; Cohen, R.; Riou, J.P.; Beylot, M. )

    1990-09-01

    To study the interactions of physiological glucagon and free fatty acids (FFA) concentrations with insulin in the control of glucose metabolism, we determined in normal subjects the response of endogenous glucose production (EGP) and glucose utilization (Rd) to a progressive and moderate increase of insulinemia in the presence of glucagon and FFA levels either decreased (somatostatin (SRIF) and insulin infusion, C test) or maintained to normal postabsorptive values isolated (SRIF + insulin + glucagon infusion, G test; SRIF + insulin + Intralipid infusion, IL test) or in association (SRIF + insulin + glucagon + Intralipid infusion, IL + G test). Compared with the C test, maintenance of glucagon level had only small and inconsistent effects on glucose Rd, but induced a shift to the right of the dose-response curve to insulin of EGP (apparent ED50: C test, 10.9 mU.L-1; G test, 15.2 mU.L-1). Intralipid infusion resulted, whether glucagon was substituted or not, in a near total suppression of the insulin-induced increase of glucose Rd (Rd at the end of the tests: C test, 6.13 +/- 0.85 mg.kg-1.min-1; G test, 7.29 +/- 0.87 mg.kg-1.min-1; IL test, 3.30 +/- 0.65 mg.kg-1.min-1; IL + G test, 3.57 +/- 0.42 mg.kg-1.min-1). In the absence of glucagon, substitution Intralipid infusion also antagonized the action of insulin on EGP. However, this effect was no longer apparent when glucagon was replaced (dose-response curve to insulin of EGP during the G and the IL + G test were comparable).

  14. Effect of Naloxon on Counter Insulin Hormone Secretion in Insulin-Induced Hypoglycemia

    PubMed Central

    Ju, Yeong Shil; Kim, Sung Woon; Yang, In Myung; Kim, Jin Woo; Kim, Young Seol; Choi, Young Kil

    1987-01-01

    To investigate the normal physiologic role of endogenous opiates in glucose homeostasis and as a preliminary study for clarifying the association of endogenous opites with pathophysilogy of NIDDM, we obseved the changes in the secretion of counter-insulin hormones in response to insulin-induced hypoglycemia with or without naloxone. The results were as follows: Blood glucose was decreased significantly more rapidly with naloxone infusion than after insulin alone, which seems to play a role in the early responses of ACTH and GH.Not only was the more rapid response of ACTH and GH, but also the prolonged secretion of ACTH and Cortisol were observed after administration of insulin and naloxone. We concluded that endogenous opiates may be involved in the feedback regulation of secretion of ACTH and GH during hypoglycemia either at hypophysis or hypothalamus, and involved in glucose homeostasis via a certain direct mechanism other than regulation of counter hormone secretion. PMID:2856480

  15. Endothelial function and insulin sensitivity during acute non-esterified fatty acid elevation: Effects of fat composition and gender

    PubMed Central

    Newens, K.J.; Thompson, A.K.; Jackson, K.G.; Williams, C.M.

    2015-01-01

    Background and aims We have reported that adverse effects on flow-mediated dilation of an acute elevation of non-esterified fatty acids rich in saturated fat (SFA) are reversed following addition of long-chain (LC) n-3 polyunsaturated fatty acids (PUFA), and hypothesised that these effects may be mediated through alterations in insulin signalling pathways. In a subgroup, we explored the effects of raised NEFA enriched with SFA, with or without LC n-3 PUFA, on whole body insulin sensitivity (SI) and responsiveness of the endothelium to insulin infusion. Methods and results Thirty adults (mean age 27.8 y, BMI 23.2 kg/m2) consumed oral fat loads on separate occasions with continuous heparin infusion to elevate NEFA between 60 and 390 min. For the final 150 min, a hyperinsulinaemic-euglycaemic clamp was performed, whilst FMD and circulating markers of endothelial function were measured at baseline, pre-clamp (240 min) and post-clamp (390 min). NEFA elevation during the SFA-rich drinks was associated with impaired FMD (P = 0.027) whilst SFA + LC n-3 PUFA improved FMD at 240 min (P = 0.003). In males, insulin infusion attenuated the increase in FMD with SFA + LC n-3 PUFA (P = 0.049), with SI 10% greater with SFA + LC n-3 PUFA than SFA (P = 0.041). Conclusion This study provides evidence that NEFA composition during acute elevation influences both FMD and SI, with some indication of a difference by gender. However our findings are not consistent with the hypothesis that the effects of fatty acids on endothelial function and SI operate through a common pathway. This trial was registered at clinical trials.gov as NCT01351324 on 6th May 2011. PMID:25921849

  16. Insulin-like growth factor-I (IGF-I) analogue, LR(3)IGF-I, ameliorates the loss of body weight but not of skeletal muscle during food restriction.

    PubMed

    Tomas, F M

    2001-04-01

    Insulin-like growth factor-I (IGF-I) is known to have anabolic effects in freely fed rats. We have investigated the ability of infused LR(3)IGF-I, an analogue of IGF-I, to attenuate the loss of lean tissue due to food restriction in young (5 weeks) and adult (12 weeks) rats. Groups of rats received food at 100%, 78%, 56% or 33% of ad libitum levels. Within each nutrition group the rats were continuously infused with LR(3)IGF-I at (98 nmol/day)/kg body weight or vehicle for 7 days. At each level of food intake, rats infused with LR(3)IGF-I maintained higher body weight (around 3-8%;P< 0.001) and nitrogen retention (P< 0.001) than those infused with vehicle alone but muscle protein was not conserved. LR(3)IGF-I infusion increased fat loss only in young rats (P< 0.05) despite a reduction in plasma insulin levels in both age groups (P< 0.01). Muscle protein turnover rates were unaffected by LR(3)IGF-I in young rats. In adult rats LR(3)IGF-I exacerbated the effects of food restriction through increased rates of protein breakdown, reduced RNA content and reduced rates of protein synthesis (P< 0.05) despite their larger fat reserves. Although young and adult rats show differing metabolic responses, we conclude that infusion of LR(3)IGF-I to either group during short-term food restriction does not ameliorate the loss of lean tissue by allowing more efficient utilization and/or partitioning of nutrients. PMID:11472075

  17. Selective Insulin Resistance in the Kidney

    PubMed Central

    Horita, Shoko; Nakamura, Motonobu; Suzuki, Masashi; Satoh, Nobuhiko; Suzuki, Atsushi; Seki, George

    2016-01-01

    Insulin resistance has been characterized as attenuation of insulin sensitivity at target organs and tissues, such as muscle and fat tissues and the liver. The insulin signaling cascade is divided into major pathways such as the PI3K/Akt pathway and the MAPK/MEK pathway. In insulin resistance, however, these pathways are not equally impaired. For example, in the liver, inhibition of gluconeogenesis by the insulin receptor substrate (IRS) 2 pathway is impaired, while lipogenesis by the IRS1 pathway is preserved, thus causing hyperglycemia and hyperlipidemia. It has been recently suggested that selective impairment of insulin signaling cascades in insulin resistance also occurs in the kidney. In the renal proximal tubule, insulin signaling via IRS1 is inhibited, while insulin signaling via IRS2 is preserved. Insulin signaling via IRS2 continues to stimulate sodium reabsorption in the proximal tubule and causes sodium retention, edema, and hypertension. IRS1 signaling deficiency in the proximal tubule may impair IRS1-mediated inhibition of gluconeogenesis, which could induce hyperglycemia by preserving glucose production. In the glomerulus, the impairment of IRS1 signaling deteriorates the structure and function of podocyte and endothelial cells, possibly causing diabetic nephropathy. This paper mainly describes selective insulin resistance in the kidney, focusing on the proximal tubule. PMID:27247938

  18. Resveratrol prevents insulin resistance caused by short-term elevation of free fatty acids in vivo.

    PubMed

    Pereira, Sandra; Park, Edward; Moore, Jessy; Faubert, Brandon; Breen, Danna M; Oprescu, Andrei I; Nahle, Ashraf; Kwan, Denise; Giacca, Adria; Tsiani, Evangelia

    2015-11-01

    Elevated levels of plasma free fatty acids (FFA), which are commonly found in obesity, induce insulin resistance. FFA activate protein kinases including the proinflammatory IκBα kinase β (IKKβ), leading to serine phosphorylation of insulin receptor substrate 1 (IRS-1) and impaired insulin signaling. To test whether resveratrol, a polyphenol found in red wine, prevents FFA-induced insulin resistance, we used a hyperinsulinemic-euglycemic clamp with a tracer to assess hepatic and peripheral insulin sensitivity in overnight-fasted Wistar rats infused for 7 h with saline, Intralipid plus 20 U·mL(-1) heparin (IH; triglyceride emulsion that elevates FFA levels in vivo; 5.5 μL·min(-1)) with or without resveratrol (3 mg·kg(-1)·h(-1)), or resveratrol alone. Infusion of IH significantly decreased glucose infusion rate (GIR; P < 0.05) and peripheral glucose utilization (P < 0.05) and increased endogenous glucose production (EGP; P < 0.05) during the clamp compared with saline infusion. Resveratrol co-infusion, however, completely prevented the effects induced by IH infusion: it prevented the decreases in GIR (P < 0.05 vs. IH), peripheral glucose utilization (P < 0.05 vs. IH), and insulin-induced suppression of EGP (P < 0.05 vs. IH). Resveratrol alone had no effect. Furthermore, IH infusion increased serine (307) phosphorylation of IRS-1 in soleus muscle (∼30-fold, P < 0.001), decreased total IRS-1 levels, and decreased IκBα content, consistent with activation of IKKβ. Importantly, all of these effects were abolished by resveratrol (P < 0.05 vs. IH). These results suggest that resveratrol prevents FFA-induced hepatic and peripheral insulin resistance and, therefore, may help mitigate the health consequences of obesity. PMID:26455923

  19. Effect of combined application insulin and insulin detemir on continous glucose monitor in children with type 1 diabetes mellitus

    PubMed Central

    Chen, Xiao-Yun; Dong, Qing; Li, Gui-Mei

    2015-01-01

    Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action, which could strengthen the effects of insulin. This study aims to explore the effects of insulin combined with insulin detemir on the continous glucose in children with type 1 diabetes mellitus. In this study, 150 patients with type 1 diabetes enrolled were included and randomly divided into 3 groups: insulin group (group A), insulin detemir group (group B) and insulin combined with insulin detemir group (group C). Each subject underwent 72 h of continuous glucose monitoring (CGM). MAGE, HbA1c and Noctumal Hypoglycemia levels were examined by using the ELISA kits. The body weight changes were also detected in this study. The results indicated that the information including age, body weight, disease duration and glucose level and HbA1c percentage on the start time point among three groups indicated no statistical differences. Insulin combined with insulin detemir decrease MAGE and HbA1c level in Group C compared to Group A and Group A (P < 0.05). Insulin combined with insulin detemir decreas noctumal hypoglycemia levels and body weight changes (P < 0.05). In conclusion, this study confirmed efficacy of insulin detemir by demonstrating non-inferiority of insulin detemir compared with insulin with respect to HbA1c, with an improved safety profile including significantly fewer hypoglycaemic episodes and less undesirable weight gain in children. PMID:26064343

  20. A simple method for quantitation of insulin sensitivity and insulin release from an intravenous glucose tolerance test.

    PubMed

    Galvin, P; Ward, G; Walters, J; Pestell, R; Koschmann, M; Vaag, A; Martin, I; Best, J D; Alford, F

    1992-12-01

    Both insulin secretion and insulin sensitivity are important in the development of diabetes but current methods used for their measurements are complex and cannot be used for epidemiological surveys. This study describes a simplified approach for the estimation of first phase insulin release and insulin sensitivity from a standard 40-min intravenous glucose tolerance test (IVGTT), and compares these parameter estimations with the sophisticated minimal model analysis of a frequently sampled 3-h IVGTT and the euglycaemic clamp technique. For the simplified IVGTT, first phase insulin release was measured as the insulin area above basal post glucose load unit-1 incremental change (i.e. peak rise) in plasma glucose over 0-10 min, and insulin sensitivity as a rate of glucose disappearance (Kg) unit-1 insulin increase above basal from 0-40 min post-glucose load in 18 subjects who were studied twice, either basally or in a perturbed pathophysiological state (i.e. pre- and post-ultramarathon race, n = 5; pre- and post-20 h pulsatile hyperinsulinaemia, n = 8; pre- and post-thyrotoxic state, n = 5). A further 12 subjects were compared by IVGTT, and glucose clamp. In addition, seven dogs were studied three times by IVGTT during normal saline infusion and after short-term (1/2 hour) or long-term (72 hour) adrenaline infusions. First phase insulin release and insulin sensitivity estimated from the simplified IVGTT as calculated by the two methods correlated closely (rs = 0.89 and rs = 0.87, respectively), although less precisely in markedly insulin-resistant subjects and the slopes and y intercepts of the linear regression lines were similar in the basal and perturbed states.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1478037

  1. Professional ethics. A case study of infusion nurse consultants.

    PubMed

    Adams, J

    2000-01-01

    As the healthcare system continues to reform, opportunities exist for infusion nurses to expand their practice into the business world. Traditionally, biomedical ethics have been used in nursing education as a framework for identifying and responding to ethical dilemmas. However, in the business world, professional ethics may be more subtle and insidious. A case study of ten infusion nurse consultants and their experiences with professional ethical issues is presented. Data were obtained using interviews, and content analysis revealed emergent themes of integrity and intuitive knowing with related categories. PMID:11847709

  2. Infusing Culture in Career Counseling

    ERIC Educational Resources Information Center

    Arthur, Nancy; Collins, Sandra

    2011-01-01

    This article introduces the culture-infused career counselling (CICC) model. Six principles are foundational to a tripartite model emphasizing cultural self-awareness, awareness of client cultural identities, and development of a culturally sensitive working alliance. The core competencies ensure the cultural validity and relevance of career…

  3. Infusing Service Learning into Instruction.

    ERIC Educational Resources Information Center

    Arrington, Harriette J.; Moore, Sara Delano

    2001-01-01

    Describes how service learning can link to the middle school curriculum to strengthen the learning of various skills and concepts. Presents service learning model involving preparation, action, reflection, and recognition. Includes examples of effective infusion of service learning into units, lessons, and projects. Concludes with recommendations…

  4. Enhancing Instruction through Software Infusion.

    ERIC Educational Resources Information Center

    Sia, Archie P.

    The presence of the computer in the classroom is no longer considered an oddity; it has become an ordinary resource for teachers to use for the enhancement of instruction. This paper presents an examination of software infusion, i.e., the use of computer software to enrich instruction in an academic curriculum. The process occurs when a chosen…

  5. Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

    SciTech Connect

    Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

    2013-02-01

    Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

  6. In-Use Contamination of Intravenous Infusion Fluid

    PubMed Central

    Maki, Dennis G.; Anderson, Roger L.; Shulman, Jonas A.

    1974-01-01

    During the 1970 to 1971 nationwide epidemic of septicemias caused by Enterobacter cloacae and Enterobacter agglomerans traced to intrinsic contamination of Abbott intravenous infusion products, 94 infusion systems manufactured by Baxter Laboratories were studied microbiologically and epidemiologically during hospital use. Intravenous fluid from 10 systems (11%) contained microorganisms, usually Staphylococcus or Bacillus species; one infusion was heavily contaminated with Klebsiella pneumoniae. No national epidemic organisms, E. cloacae or E. agglomerans (formerly Erwinia), were recovered, suggesting that during this period frequent contamination with these organisms was unique to Abbott's infusion products. Contamination in this study appeared to be extrinsic in origin (introduced during clinical use) and related to the duration of continuous intravenous therapy. Nine of 61 systems (15%) that had been used longer than 48 h were contaminated, whereas only 1 of 33 used less than 48 h (3%) contained microorganisms. This study and the recent national outbreak indicate that contamination of infusion fluid, both from intrinsic and extrinsic sources, must be recognized as an additional risk of intravenous therapy; however, a once-daily replacement of the delivery apparatus can significantly diminish this hazard. PMID:4613269

  7. High-technology i.v. infusion devices.

    PubMed

    Kwan, J W

    1989-02-01

    Some of the newer high-technology infusion devices commercially available or under development are described. The range of infusion devices includes both controllers and pumps; pumps can be classified by mechanism of operation (peristaltic, syringe, cassette, elastomeric reservoir), frequency or type of drug delivery (continuous or intermittent infusion, bolus dosing, single- or multiple-solution delivery), or therapeutic application (such as the patient-controlled analgesia, or PCA, pump). Advances in infusion technology and computer technology have led to the development of devices with extremely sophisticated drug-delivery capabilities (multiple-rate or multiple-solution programming, operation as pump or controller, or both, and interchangeable applications and settings). Current research in infusion-device technology is focusing on implantable pumps, pumps with chronobiological applications, osmotic-pressure devices, and open- and closed-loop systems. Pharmacists need to keep abreast of the rapidly changing intravenous device marketplace to provide clinical expertise and leadership in the review and evaluation of high-technology drug delivery systems. PMID:2653027

  8. High-technology i.v. infusion devices.

    PubMed

    Kwan, J W

    1991-10-01

    Some of the newer high-technology infusion devices commercially available or under development are described. The range of infusion devices includes both controllers and pumps; pumps can be classified by mechanism of operation (peristaltic, syringe, cassette, elastomeric reservoir), frequency or type of drug delivery (continuous or intermittent infusion, bolus dosing, single- or multiple-solution delivery), or therapeutic application (such as the patient-controlled analgesia, or PCA, pump). Advances in infusion technology and computer technology have led to the development of devices with extremely sophisticated drug-delivery capabilities (multiple-rate or multiple-solution programming, operation as pump or controller, or both, and interchangeable applications and settings). Current research in infusion-device technology is focusing on implantable pumps, pumps with chronobiological applications, osmotic-pressure devices, and open- and closed-loop systems. Pharmacists need to keep abreast of the rapidly changing intravenous device marketplace to provide clinical expertise and leadership in the review and evaluation of high-technology drug delivery systems. PMID:1772112

  9. Local distribution and toxicity of prolonged hippocampal infusion of muscimol

    PubMed Central

    Heiss, John D.; Walbridge, Stuart; Morrison, Paul; Hampton, Robert R.; Sato, Susumu; Vortmeyer, Alexander; Butman, John A.; O’Malley, James; Vidwan, Param; Dedrick, Robert L.; Oldfield, Edward H.

    2014-01-01

    Object The activity of γ-aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is reduced in the hippocampus in patients with complex partial seizures from mesial temporal sclerosis. To provide preliminary safety and distribution data on using convection-enhanced delivery of agents to treat complex partial seizures and to test the efficacy and safety of regional selective neuronal suppression, the authors infused muscimol, a GABA-A receptor agonist, directly into the hippocampus of nonhuman primates using an integrated catheter electrode. Methods Ten rhesus monkeys were divided into three groups: 1) use of catheter electrode alone (four monkeys); 2) infusion of escalating concentrations of muscimol followed by vehicle (three monkeys); and 3) infusion of vehicle and subsequent muscimol mixed with muscimol tracer (three monkeys). Infusions were begun 5 days after catheter electrode placement and continued for 5.6 days before switching to the other agent. Head magnetic resonance (MR) images and electroencephalography recordings were obtained before and during the infusions. Brain histological studies and quantitative autoradiography were performed. Neurological function was normal in controls and when muscimol concentrations were 0.125 mM or less, whereas higher concentrations (0.5 and 1 mM) produced reversible apathy and somnolence. Fluid distribution was demonstrated on MR images and muscimol distribution was demonstrated on autoradiographs throughout the hippocampus and adjacent white matter. Conclusions Targeted modulation of neuronal activity is a reasonable research strategy for the investigation and treatment of medically intractable epilepsy. PMID:16381190

  10. Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance

    PubMed Central

    Ueyama, Atsunori; Ban, Nobuhiro; Fukazawa, Masanori; Hirayama, Tohru; Takeda, Minako; Yata, Tatsuo; Muramatsu, Hiroyasu; Hoshino, Masaki; Yamamoto, Marii; Matsuo, Masao; Kawashima, Yuka; Iwase, Tatsuhiko; Kitazawa, Takehisa; Kushima, Youichi; Yamada, Yuichiro; Kawabe, Yoshiki

    2016-01-01

    Although mitogen-activated protein kinase kinase (MEK) is a key signaling molecule and a negative regulator of insulin action, it is still uncertain whether MEK can be a therapeutic target for amelioration of insulin resistance (IR) in type 2 diabetes (T2D) in vivo. To clarify whether MEK inhibition improves T2D, we examined the effect of continuous MEK inhibition with two structurally different MEK inhibitors, RO5126766 and RO4987655, in mouse models of T2D. RO5126766 and RO4987655 were administered via dietary admixture. Both compounds decreased blood glucose and improved glucose tolerance in doses sufficient to sustain inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation downstream of MEK in insulin-responsive tissues in db/db mice. A hyperinsulinemic-euglycemic clamp test showed increased glucose infusion rate (GIR) in db/db mice treated with these compounds, and about 60% of the increase was attributed to the inhibition of endogenous glucose production, suggesting that the liver is responsible for the improvement of IR. By means of adenovirus-mediated Mek1 shRNA expression, we confirmed that blood glucose levels are reduced by suppression of MEK1 expression in the liver of db/db mice. Taken together, these results suggested that the MEK signaling pathway could be a novel therapeutic target for novel antidiabetic agents. PMID:26839898

  11. Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance.

    PubMed

    Ueyama, Atsunori; Ban, Nobuhiro; Fukazawa, Masanori; Hirayama, Tohru; Takeda, Minako; Yata, Tatsuo; Muramatsu, Hiroyasu; Hoshino, Masaki; Yamamoto, Marii; Matsuo, Masao; Kawashima, Yuka; Iwase, Tatsuhiko; Kitazawa, Takehisa; Kushima, Youichi; Yamada, Yuichiro; Kawabe, Yoshiki

    2016-01-01

    Although mitogen-activated protein kinase kinase (MEK) is a key signaling molecule and a negative regulator of insulin action, it is still uncertain whether MEK can be a therapeutic target for amelioration of insulin resistance (IR) in type 2 diabetes (T2D) in vivo. To clarify whether MEK inhibition improves T2D, we examined the effect of continuous MEK inhibition with two structurally different MEK inhibitors, RO5126766 and RO4987655, in mouse models of T2D. RO5126766 and RO4987655 were administered via dietary admixture. Both compounds decreased blood glucose and improved glucose tolerance in doses sufficient to sustain inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation downstream of MEK in insulin-responsive tissues in db/db mice. A hyperinsulinemic-euglycemic clamp test showed increased glucose infusion rate (GIR) in db/db mice treated with these compounds, and about 60% of the increase was attributed to the inhibition of endogenous glucose production, suggesting that the liver is responsible for the improvement of IR. By means of adenovirus-mediated Mek1 shRNA expression, we confirmed that blood glucose levels are reduced by suppression of MEK1 expression in the liver of db/db mice. Taken together, these results suggested that the MEK signaling pathway could be a novel therapeutic target for novel antidiabetic agents. PMID:26839898

  12. β-Adrenergic Responsive Induction of Insulin Resistance in Liver of Aging Rats.

    PubMed

    Muscogiuri, Giovanna; Kamat, Amrita; Balas, Bogdan; Giaccari, Andrea; Defronzo, Ralph A; Musi, Nicolas; Katz, Michael S

    2011-01-01

    INTRODUCTION. We previously demonstrated increases in β-adrenergic receptor (β-AR) density in rat liver, in association with increased β-AR-mediated stimulation of glucose output in rat hepatocytes, during senescent aging. We therefore hypothesized that pharmacologic β-adrenergic stimulation might induce insulin resistance and glucose output in liver of aging rats in vivo. METHODS. In this study, pancreatic clamps were performed on young adult (4-month-old) and senescent (24-month-old) Fischer 344 male rats by infusing somatostatin (3 μg/kg/min) at time 0 to inhibit insulin secretion, and then infusing insulin (1 mU/kg/min) to replace basal insulin concentrations. At time 0 rats also received either the β-AR agonist isoproterenol (100 ng/kg/min) or saline (control). After 120 min the insulin infusion rate was increased to 4 mU/kg/min for an additional 120 min. Tritiated glucose was infused throughout the study to measure glucose turnover rates. RESULTS AND CONCLUSION. The results of the pancreatic clamp studies demonstrated that under saline control conditions hepatic glucose production (HGP) was suppressed during hyperinsulinemia in both young and old rats, with a trend toward reduced insulin sensitivity in the older animals. Isoproterenol infusion impaired insulin-induced suppression of HGP in both age groups. The results suggest that β-AR stimulation by isoproterenol increases HGP and acutely induces hepatic insulin resistance in both young and old rats. A similar role for β-adrenergic-mediated hepatic insulin resistance in aging humans would suggest a novel therapeutic target for the treatment or prevention of glucose dysregulation and diabetes developing with advancing age. PMID:21438725

  13. Insulin Human Inhalation

    MedlinePlus

    Insulin inhalation is used in combination with a long-acting insulin to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar ...

  14. Giving an insulin injection

    MedlinePlus

    ... One Type of Insulin Wash your hands with soap and water. Dry them well. Check the insulin ... syringe before injecting it. Wash your hands with soap and water. Dry them well. Check the insulin ...

  15. Insulin Lispro Injection

    MedlinePlus

    ... is a short-acting, man-made version of human insulin. Insulin lispro works by replacing the insulin ... niacin (Niacor, Niaspan, in Advicor); certain medications for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) ...

  16. Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children

    PubMed Central

    Fram, Ricki Y.; Cree, Melanie G.; Wolfe, Robert R.; Mlcak, Ronald P.; Qian, Ting; Chinkes, David L.; Herndon, David N.

    2013-01-01

    Objective To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. Design Prospective, randomized study. Setting An acute pediatric burn unit in a tertiary teaching hospital. Patients Children, 4–18 yrs old, with total body surface area burned ≥40% and who arrived within 1 wk after injury were enrolled in the study. Interventions Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose ≤215 mg/dL. Measurements and Main Results Twenty patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days post-burn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 ± 124 to 1925 ± 291 kcal/m2·day; p = .02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 ± 0.8 conventional insulin therapy vs. 6.8 ± 0.9 mg/kg·min intensive insulin therapy; p = .5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 ± 1.3 intensive insulin therapy versus 4.8 ± 0.6 mg/kg·min conventional insulin therapy, p = .005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 ± 0.9 vs. 2.5 ± 0.6 mg/kg·min; intensive insulin therapy vs. conventional insulin therapy; p = .03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 ± 0.1 to 1.7 ± 0.1 μm O2/CS/mg protein/min for state 3, p = .004; and 0.7 ± 0.1 to 1.3 ± 0.1 μm O2/CS/mg protein

  17. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or...

  18. 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

  19. Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus

    PubMed Central

    Boering, M; Logtenberg, S J J; Groenier, K H; Wolffenbuttel, B H R; Gans, R O B; Kleefstra, N; Bilo, H J G

    2016-01-01

    Aims Elevated sex hormone-binding globulin (SHBG) concentrations have been described in patients with type 1 diabetes mellitus (T1DM), probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII), or subcutaneous (SC), influences SHBG concentrations among T1DM patients. Methods Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13) years, diabetes duration 23 (±11) years, and hemoglobin A1c (HbA1c) 8.7 (±1.1) (72 (±12) mmol/mol). As secondary outcomes, testosterone, 17-β-estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were analyzed. Results Estimated mean change in SHBG was −10.3nmol/L (95% CI: −17.4, −3.2) during CIPII and 3.7nmol/L (95% CI: −12.0, 4.6) during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was −6.6nmol/L (95% CI: −17.5, 4.3); −12.7nmol/L (95% CI: −25.1, −0.4) for males and −1.7nmol/L (95% CI: −24.6, 21.1) for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; −15.8nmol/L (95% CI: −24.2, −7.5) and −8.3nmol/L (95% CI: −14.4, −2.2), respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2) among males. Conclusions SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids. PMID:27287189

  20. Hemodynamic responses of the equine digit to intravenous and digital arterial infusion of dopamine.

    PubMed

    Hunt, R J; Moore, J N; Allen, D

    1990-04-01

    In 6 adult horses anesthetized with pentobarbital, the hemodynamic responses of the equine digit to infusion of dopamine were evaluated by use of an isolated extra corporeal pump perfused digital preparation. Digital blood flow was maintained at a constant rate that was independent of systemic hemodynamic changes. Three sequential experiments were performed on each horse. In the first experiment (n = 6), dopamine was infused IV at rates of 1.0, 2.5, and 5.0 micrograms/kg/min. For the second experiment (n = 5), dopamine (400 micrograms/ml) was infused into the digital artery at the rates of 0.07, 0.7, and 1.2 ml/min. The third experiment (n = 5) consisted of a 5-minute intra-arterial infusion of phentolamine followed by the intra-arterial infusion of dopamine while continuing the infusion of phentolamine. Digital venous, arterial, and capillary pressures, total digital vascular resistance, and precapillary to postcapillary resistance ratios were determined in each experiment. Systemic infusion of dopamine did not induce changes in the hemodynamics of the digital vasculature. Digital arterial infusion of dopamine alone resulted in a dose-dependent increase in arterial pressure, total digital vascular resistance, and an increase in the precapillary to postcapillary resistance ratio. Phentolamine attenuated the vasoconstrictive response elicited by intra-arterial infusion of dopamine. PMID:2327616

  1. Reconstituted high-density lipoprotein infusion modulates fatty acid metabolism in patients with type 2 diabetes mellitus

    PubMed Central

    Drew, Brian G.; Carey, Andrew L.; Natoli, Alaina K.; Formosa, Melissa F.; Vizi, Donna; Reddy-Luthmoodoo, Medini; Weir, Jacquelyn M.; Barlow, Christopher K.; van Hall, Gerrit; Meikle, Peter J.; Duffy, Stephen J.; Kingwell, Bronwyn A.

    2011-01-01

    We recently demonstrated that reconstituted high-density lipoprotein (rHDL) modulates glucose metabolism in humans via both AMP-activated protein kinase (AMPK) in muscle and by increasing plasma insulin. Given the key roles of both AMPK and insulin in fatty acid metabolism, the current study investigated the effect of rHDL infusion on fatty acid oxidation and lipolysis. Thirteen patients with type 2 diabetes received separate infusions of rHDL and placebo in a randomized, cross-over study. Fatty acid metabolism was assessed using steady-state tracer methodology, and plasma lipids were measured by mass spectrometry (lipidomics). In vitro studies were undertaken in 3T3-L1 adipocytes. rHDL infusion inhibited fasting-induced lipolysis (P = 0.03), fatty acid oxidation (P < 0.01), and circulating glycerol (P = 0.04). In vitro, HDL inhibited adipocyte lipolysis in part via activation of AMPK, providing a possible mechanistic link for the apparent reductions in lipolysis observed in vivo. In contrast, circulating NEFA increased after rHDL infusion (P < 0.01). Lipidomic analyses implicated phospholipase hydrolysis of rHDL-associated phosphatidylcholine as the cause, rather than lipolysis of endogenous fat stores. rHDL infusion inhibits fasting-induced lipolysis and oxidation in patients with type 2 diabetes, potentially through both AMPK activation in adipose tissue and elevation of plasma insulin. The phospholipid component of rHDL also has the potentially undesirable effect of increasing circulating NEFA. PMID:21224289

  2. Comparative effect of intraduodenal and intrajejunal glucose infusion on the gut-incretin axis response in healthy males.

    PubMed

    Wu, T; Thazhath, S S; Marathe, C S; Bound, M J; Jones, K L; Horowitz, M; Rayner, C K

    2015-01-01

    The region of enteral nutrient exposure may be an important determinant of postprandial incretin hormone secretion and blood glucose homoeostasis. We compared responses of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and blood glucose to a standardised glucose infusion into the proximal jejunum and duodenum in healthy humans. Ten healthy males were evaluated during a standardised glucose infusion (2 kcal min(-1) over 120 min) into the proximal jejunum (50 cm post pylorus) and were compared with another 10 healthy males matched for ethnicity, age and body mass index who received an identical glucose infusion into the duodenum (12 cm post pylorus). Blood was sampled frequently for measurements of blood glucose and plasma hormones. Plasma GLP-1, GIP and insulin responses, as well as the insulin:glucose ratio and the insulinogenic index 1 (IGI1) were greater (P<0.05 for each) after intrajejunal (i.j.) than intraduodenal glucose infusion, without a significant difference in blood glucose or plasma glucagon. Pooled analyses revealed direct relationships between IGI1 and the responses of GLP-1 and GIP (r=0.48 and 0.56, respectively, P<0.05 each), and between glucagon and GLP-1 (r=0.70, P<0.001). In conclusion, i.j. glucose elicits greater incretin hormone and insulin secretion than intraduodenal glucose in healthy humans, suggesting regional specificity of the gut-incretin axis. PMID:25985092

  3. Acute IGF-I infusion stimulates whole body protein synthesis but does not reduce proteolysis in neonates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Skeletal muscle protein synthesis increases in response to a physiological rise in total insulin-like growth factor I (IGF-I) in neonatal pigs. To determine the response of whole body protein synthesis and degradation to IGF-I, fasted 7-day-old pigs (n=4/dose) were infused with IGF-I (0, 20, or 50 ...

  4. Hepatic and Whole-Body Insulin Metabolism during Proestrus and Estrus in Mongrel Dogs.

    PubMed

    Yu, Erin Nz; Winnick, Jason J; Edgerton, Dale S; Scott, Melanie F; Smith, Marta S; Farmer, Ben; Williams, Phillip E; Cherrington, Alan D; Moore, Mary Courtney

    2016-01-01

    Insulin resistance occurs during various stages of the estrus cycle in dogs. To quantify the effects of proestrus-estrus (PE) and determine whether PE affects liver insulin sensitivity, 11 female mongrel dogs were implanted with sampling and intraportal infusion catheters. Five of the dogs (PE group) entered proestrus after surgery; those remaining in anestrus were controls. The dogs were fasted overnight, [3-(3)H]glucose and somatostatin were infused through peripheral veins, and glucagon was infused intraportally. Insulin was infused intraportally, with the rate adjusted to maintain arterial plasma glucose at basal levels (PE, 294±25 μU/kg/min; control, 223±21 μU/kg/min). Subsequently the insulin infusion rate was increased by 0.2 mU/kg/min for 120 min (P1) and then to 1.5 mU/kg/min for the last 120 min (P2); glucose was infused peripherally as needed to maintain euglycemia. Insulin concentrations did not differ between groups at any time; they increased 3 μU/mL over baseline during P1 and to 3 times baseline during P2. The glucose infusion rate in PE dogs during P2 was 63% of that in control dogs. Net hepatic glucose output and the endogenous glucose production rate declined 40% to 50% from baseline in both groups during P1; during P2, both groups exhibited a low rate of net hepatic glucose uptake with full suppression of endogenous glucose production. The glucose disappearance rate during P1 and P2 was 35% greater in control than PE dogs. Therefore, PE in canines is associated with loss of nonhepatic (primarily muscle) but not hepatic insulin sensitivity. PMID:27298249

  5. Assessment of Patient-Led or Physician-Driven Continuous Glucose Monitoring in Patients With Poorly Controlled Type 1 Diabetes Using Basal-Bolus Insulin Regimens

    PubMed Central

    Riveline, Jean-Pierre; Schaepelynck, Pauline; Chaillous, Lucy; Renard, Eric; Sola-Gazagnes, Agnès; Penfornis, Alfred; Tubiana-Rufi, Nadia; Sulmont, Véronique; Catargi, Bogdan; Lukas, Céline; Radermecker, Régis P.; Thivolet, Charles; Moreau, François; Benhamou, Pierre-Yves; Guerci, Bruno; Leguerrier, Anne-Marie; Millot, Luc; Sachon, Claude; Charpentier, Guillaume; Hanaire, Hélène

    2012-01-01

    OBJECTIVE The benefits of real-time continuous glucose monitoring (CGM) have been demonstrated in patients with type 1 diabetes. Our aim was to compare the effect of two modes of use of CGM, patient led or physician driven, for 1 year in subjects with poorly controlled type 1 diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes aged 8–60 years with HbA1c ≥8% were randomly assigned to three groups (1:1:1). Outcomes for glucose control were assessed at 1 year for two modes of CGM (group 1: patient led; group 2: physician driven) versus conventional self-monitoring of blood glucose (group 3: control). RESULTS A total of 257 subjects with type 1 diabetes underwent screening. Of these, 197 were randomized, with 178 patients completing the study (age: 36 ± 14 years; HbA1c: 8.9 ± 0.9%). HbA1c improved similarly in both CGM groups and was reduced compared with the control group (group 1 vs. group 3: −0.52%, P = 0.0006; group 2 vs. group 3: −0.47%, P = 0.0008; groups 1 + 2 vs. group 3: −0.50%, P < 0.0001). The incidence of hypoglycemia was similar in the three groups. Patient SF-36 questionnaire physical health score improved in both experimental CGM groups (P = 0.004). Sensor consumption was 34% lower in group 2 than in group 1 (median [Q1–Q3] consumption: group 1: 3.42/month [2.20–3.91] vs. group 2: 2.25/month [1.27–2.99], P = 0.001). CONCLUSIONS Both patient-led and physician-driven CGM provide similar long-term improvement in glucose control in patients with poorly controlled type 1 diabetes, but the physician-driven CGM mode used fewer sensors. PMID:22456864

  6. 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

  7. Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling.

    PubMed

    Hong, Eun-Gyoung; Jung, Dae Young; Ko, Hwi Jin; Zhang, Zhiyou; Ma, Zhexi; Jun, John Y; Kim, Jae Hyeong; Sumner, Andrew D; Vary, Thomas C; Gardner, Thomas W; Bronson, Sarah K; Kim, Jason K

    2007-12-01

    Although insulin resistance has been traditionally associated with type 2 diabetes, recent evidence in humans and animal models indicates that insulin resistance may also develop in type 1 diabetes. A point mutation of insulin 2 gene in Ins2(Akita) mice leads to pancreatic beta-cell apoptosis and hyperglycemia, and these mice are commonly used to investigate type 1 diabetes and complications. Since insulin resistance plays an important role in diabetic complications, we performed hyperinsulinemic-euglycemic clamps in awake Ins2(Akita) and wild-type mice to measure insulin action and glucose metabolism in vivo. Nonobese Ins2(Akita) mice developed insulin resistance, as indicated by an approximately 80% reduction in glucose infusion rate during clamps. Insulin resistance was due to approximately 50% decreases in glucose uptake in skeletal muscle and brown adipose tissue as well as hepatic insulin action. Skeletal muscle insulin resistance was associated with a 40% reduction in total GLUT4 and a threefold increase in PKCepsilon levels in Ins2(Akita) mice. Chronic phloridzin treatment lowered systemic glucose levels and normalized muscle insulin action, GLUT4 and PKCepsilon levels in Ins2(Akita) mice, indicating that hyperglycemia plays a role in insulin resistance. Echocardiography showed significant cardiac remodeling with ventricular hypertrophy that was ameliorated following chronic phloridzin treatment in Ins2(Akita) mice. Overall, we report for the first time that nonobese, insulin-deficient Ins2(Akita) mice develop type 2 diabetes phenotypes including peripheral and hepatic insulin resistance and cardiac remodeling. Our findings provide important insights into the pathogenesis of metabolic abnormalities and complications affecting type 1 diabetes and lean type 2 diabetes subjects. PMID:17911348

  8. DEVELOPMENTAL CHANGES IN THE FEEDING-INDUCED ACTIVATION OF THE INSULIN-SIGNALING PATHWAY IN NEONATAL PIGS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In neonatal animals, feeding stimulates skeletal muscle protein synthesis, a response that declines with development. Both the magnitude of the feeding response and its developmental decline can be reproduced by insulin infusion, suggesting that an altered responsiveness to insulin is a primary dete...

  9. Stimulation of whole body protein synthesis by insulin in neonates is dependent on the pattern of amino acids available

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin stimulates muscle protein synthesis in neonatal pigs. To determine insulin's effects on whole body protein turnover, (13)C-leucine was infused for 4 hr during hyperinsulinemic (0, 30, 100, 1000 ng/(kg(0.66)/min))-euglycemic-euaminoacidemic clamps in fasted 7-d-old pigs (n=5/dose). Trophami...

  10. Recommendations for Insulin Dose Calculator Risk Management

    PubMed Central

    2014-01-01

    Several studies have shown the usefulness of an automated insulin dose bolus advisor (BA) in achieving improved glycemic control for insulin-using diabetes patients. Although regulatory agencies have approved several BAs over the past decades, these devices are not standardized in their approach to dosage calculation and include many features that may introduce risk to patients. Moreover, there is no single standard of care for diabetes worldwide and no guidance documents for BAs, specifically. Given the emerging and more stringent regulations on software used in medical devices, the approval process is becoming more difficult for manufacturers to navigate, with some manufacturers opting to remove BAs from their products altogether. A comprehensive literature search was performed, including publications discussing: diabetes BA use and benefit, infusion pump safety and regulation, regulatory submissions, novel BAs, and recommendations for regulation and risk management of BAs. Also included were country-specific and international guidance documents for medical device, infusion pump, medical software, and mobile medical application risk management and regulation. No definitive worldwide guidance exists regarding risk management requirements for BAs, specifically. However, local and international guidance documents for medical devices, infusion pumps, and medical device software offer guidance that can be applied to this technology. In addition, risk management exercises that are algorithm-specific can help prepare manufacturers for regulatory submissions. This article discusses key issues relevant to BA use and safety, and recommends risk management activities incorporating current research and guidance. PMID:24876550

  11. Recommendations for Insulin Dose Calculator Risk Management.

    PubMed