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Sample records for vivo treatment failure

  1. Predictors of treatment failure among pulmonary tuberculosis ...

    African Journals Online (AJOL)

    Introduction: Early identification of Tuberculosis (TB) treatment failure using cost effective means is urgently needed in developing nations. The study set out to describe affordable predictors of TB treatment failure in an African setting. Objective: To determine the predictors of treatment failure among patients with sputum ...

  2. In vivo monitoring of skeletal aluminium burden in patients with renal failure

    International Nuclear Information System (INIS)

    Ellis, K.J.; Kelleher, S.; Raciti, A.; Savory, J.; Wills, M.

    1988-01-01

    In vivo neutron activation analysis was used to examine the total body and partial body (hand) aluminium levels in patients with end-stage renal failure. Patients maintained on chronic hemodialysis had higher mean body burdens of aluminium than did those clinically managed without dialysis. Approximately 70% of the patients examined indicated elevated levels of body or skeletal aluminium. A significant correlation was observed between the in vivo aluminium/calcium ratio obtained for the hand measurement and the increase in serum aluminium levels following a disferroxamine infusion test. The direct in vivo monitoring of hand Al/Ca values in patients may provide an alternate choice to bone biopsy for the detection of aluminium intoxication. (author) 15 refs.; 5 figs.; 2 tabs

  3. Effects of low-molecular-weight-chitosan on the adenine-induced chronic renal failure rats in vitro and in vivo

    Science.gov (United States)

    Zhi, Xuan; Han, Baoqin; Sui, Xianxian; Hu, Rui; Liu, Wanshun

    2015-02-01

    The effects of low-molecular-weight-chitosan (LMWC) on chronic renal failure (CRF) rats induced by adenine were investigated in vivo and in vitro. Chitosan were hydrolyzed using chitosanase at pH 6-7 and 37° for 24 h to obtain LMWC. In vitro, the effect of LMWC on the proliferation of renal tubular epithelial cells (RTEC) showed that it had no cytotoxic effect and could promote cell growth. For the in vivo experiment, chronic renal failure rats induced by adenine were randomly divided into control group, Niaoduqing group, and high-, medium- and low-dose LMWC groups. For each group, we detected serum creatinine (SCR), blood urea nitrogen (BUN), and total superoxide dismutase (T-SOD), glutathione oxidase (GSH-Px) activities of renal tissue, and obtained the ratio of kidney weight/body weight, pathological changes of kidney. The levels of serum SCR, BUN were higher in the adenine-induced rats than those in the control group, indicating that the rat chronic renal failure model worked successfully. The results after treatment showed that LMWC could reduce the SCR and BUN levels and enhance the activities/levels of T-SOD and GSH-PX in kidney compared to control group. Histopathological examination revealed that adenine-induced renal alterations were restored by LMWC at three tested dosages, especially at the low dosage of 100 mg kg-1 d-1.

  4. Failure of endodontic treatment: The usual suspects.

    Science.gov (United States)

    Tabassum, Sadia; Khan, Farhan Raza

    2016-01-01

    Inappropriate mechanical debridement, persistence of bacteria in the canals and apex, poor obturation quality, over and under extension of the root canal filling, and coronal leakage are some of the commonly attributable causes of failure. Despite the high success rate of endodontic treatment, failures do occur in a large number of cases and most of the times can be attributed to the already stated causes. With an ever increasing number of endodontic treatments being done each day, it has become imperative to avoid or minimize the most fundamental of reasons leading to endodontic failure. This paper reviews the most common causes of endodontic failure along with radiographic examples.

  5. Treatment of respiratory failure in COPD

    Directory of Open Access Journals (Sweden)

    Stephan Budweiser

    2008-12-01

    Full Text Available Stephan Budweiser1, Rudolf A Jörres2, Michael Pfeifer1,31Center for Pneumology, Hospital Donaustauf, Donaustauf, Germany; 2Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Ludwig-Maximilians-University, Munich, Germany; 3Department of Internal Medicine II, Division of Respirology, University of Regensburg, Regensburg, GermanyAbstract: Patients with advanced COPD and acute or chronic respiratory failure are at high risk for death. Beyond pharmacological treatment, supplemental oxygen and mechanical ventilation are major treatment options. This review describes the physiological concepts underlying respiratory failure and its therapy, as well as important treatment outcomes. The rationale for the controlled supply of oxygen in acute hypoxic respiratory failure is undisputed. There is also a clear survival benefit from long-term oxygen therapy in patients with chronic hypoxia, while in mild, nocturnal, or exercise-induced hypoxemia such long-term benefits appear questionable. Furthermore, much evidence supports the use of non-invasive positive pressure ventilation in acute hypercapnic respiratory failure. It application reduces intubation and mortality rates, and the duration of intensive care unit or hospital stays, particularly in the presence of mild to moderate respiratory acidosis. COPD with chronic hypercapnic respiratory failure became a major indication for domiciliary mechanical ventilation, based on pathophysiological reasoning and on data regarding symptoms and quality of life. Still, however, its relevance for long-term survival has to be substantiated in prospective controlled studies. Such studies might preferentially recruit patients with repeated hypercapnic decompensation or a high risk for death, while ensuring effective ventilation and the patients’ adherence to therapy.Keywords: respiratory failure, COPD, mechanical ventilation, non-invasive ventilation long-term oxygen therapy, chronic

  6. Diuretics as pathogenetic treatment for heart failure

    Science.gov (United States)

    Guglin, Maya

    2011-01-01

    Increased intracardiac filling pressure or congestion causes symptoms and leads to hospital admissions in patients with heart failure, regardless of their systolic function. A history of hospital admission, in turn, predicts further hospitalizations and morbidity, and a higher number of hospitalizations determine higher mortality. Congestion is therefore the driving force of the natural history of heart failure. Congestion is the syndrome shared by heart failure with preserved and reduced systolic function. These two conditions have almost identical morbidity, mortality, and survival because the outcomes are driven by congestion. A small difference in favor of heart failure with preserved systolic function comes from decreased ejection fraction and left ventricular remodeling which is only present in heart failure with decreased systolic function. The magnitude of this difference reflects the contribution of decreased systolic function and ventricular remodeling to the progression of heart failure. The only treatment available for congestion is fluid removal via diuretics, ultrafiltration, or dialysis. It is the only treatment that works equally well for heart failure with reduced and preserved systolic function because it affects congestion, the main pathogenetic feature of the disease. Diuretics are pathogenetic therapy for heart failure. PMID:21403798

  7. Processes underlying treatment success and failure in assertive community treatment.

    Science.gov (United States)

    Stull, Laura G; McGrew, John H; Salyers, Michelle P

    2012-02-01

    Processes underlying success and failure in assertive community treatment (ACT), a widely investigated treatment model for persons with severe mental illness, are poorly understood. The purpose of the current study was to examine processes in ACT by (1) understanding how consumers and staff describe the processes underlying treatment success and failure and (2) comparing processes identified by staff and consumers. Investigators conducted semi-structured interviews with 25 staff and 23 consumers from four ACT teams. Both staff and consumers identified aspects of the ACT team itself as the most critical in the process of consumer success. For failure, consumers identified consumer characteristics as most critical and staff identified lack of social relationships. Processes underlying failure were not viewed as merely the opposite of processes underlying success. In addition, there was notable disagreement between staff and consumers on important processes. Findings overlap with critical ingredients identified in previous studies, including aspects of the ACT team, social involvement and employment. In contrast to prior studies, there was little emphasis on hospitalizations and greater emphasis on not abusing substances, obtaining wants and desires, and consumer characteristics.

  8. Numerical simulation of in vivo intraosseous torsional failure of a hollow-screw oral implant

    Directory of Open Access Journals (Sweden)

    Akca Kivanc

    2006-11-01

    Full Text Available Abstract Background Owing to the complexity and magnitude of functional forces transferred to the bone-implant interface, the mechanical strength of the interface is of great importance. The purpose of this study was to determine the intraosseous torsional shear strength of an osseointegrated oral implant using 3-D finite element (FE stress analysis implemented by in vivo failure torque data of an implant. Methods A Ø 3.5 mm × 12 mm ITI® hollow screw dental implant in a patient was subjected to torque failure test using a custom-made strain-gauged manual torque wrench connected to a data acquisition system. The 3-D FE model of the implant and peri-implant circumstances was constructed. The in vivo strain data was converted to torque units (N.cm to involve in loading definition of FE analysis. Upon processing of the FE analysis, the shear stress of peri-implant bone was evaluated to assume torsional shear stress strength of the bone-implant interface. Results The in vivo torque failure test yielded 5952 μstrains at custom-made manual torque wrench level and conversion of the strain data resulted in 750 N.cm. FE revealed that highest shear stress value in the trabecular bone, 121 MPa, was located at the first intimate contact with implant. Trabecular bone in contact with external surface of hollow implant body participated shear stress distribution, but not the bone resting inside of the hollow. Conclusion The torsional strength of hollow-screw implants is basically provided by the marginal bone and the hollow part has negligible effect on interfacial shear strength.

  9. Modern treatment methods for heart failure

    Directory of Open Access Journals (Sweden)

    Bojan Vrtovec

    2011-04-01

    Full Text Available Abstract: Chronic heart failure is a clinical syndrome that can result from many cardiac diseases, the most common being cardiomyopathies and coronary artery disease. According to recent epidemiological data, heart failure is the only cardiologic entity whose prevalence is actually increasing and is present in 2–5 % of general population and in 10 % of people older than 65 years. The scope of this paper includes algorithms of initial heart failure diagnostic work-up , medical management and contemporary non-medical treatment options.

  10. Predictors of Treatment Failure among Adult Antiretroviral Treatment (ART) Clients in Bale Zone Hospitals, South Eastern Ethiopia.

    Science.gov (United States)

    Haile, Demewoz; Takele, Abulie; Gashaw, Ketema; Demelash, Habtamu; Nigatu, Dabere

    2016-01-01

    Treatment failure defined as progression of disease after initiation of ART or when the anti-HIV medications can't control the infection. One of the major concerns over the rapid scaling up of ART is the emergence and transmission of HIV drug resistant strains at the population level due to treatment failure. This could lead to the failure of basic ART programs. Thus this study aimed to investigate the predictors of treatment failure among adult ART clients in Bale Zone Hospitals, South east Ethiopia. Retrospective cohort study was employed in four hospitals of Bale zone named Goba, Robe, Ginir and Delomena. A total of 4,809 adult ART clients were included in the analysis from these four hospitals. Adherence was measured by pill count method. The Kaplan Meier (KM) curve was used to describe the survival time of ART patients without treatment failure. Bivariate and multivariable Cox proportional hazards regression models were used for identifying associated factors of treatment failure. The incidence rate of treatment failure was found 9.38 (95% CI 7.79-11.30) per 1000 person years. Male ART clients were more likely to experience treatment failure as compared to females [AHR = 4.49; 95% CI: (2.61-7.73)].Similarly, lower CD4 count (ART was found significantly associated with higher odds of treatment failure [AHR = 3.79; 95% CI: (2.46-5.84).Bedridden [AHR = 5.02; 95% CI: (1.98-12.73)] and ambulatory [AHR = 2.12; 95% CI: (1.08-4.07)] patients were more likely to experience treatment failure as compared to patients with working functional status. TB co-infected clients had also higher odds to experience treatment failure [AHR = 3.06; 95% CI: (1.72-5.44)]. Those patients who had developed TB after ART initiation had higher odds to experience treatment failure as compared to their counter parts [AHR = 4.35; 95% CI: (1.99-9.54]. Having other opportunistic infection during ART initiation was also associated with higher odds of experiencing treatment failure [AHR = 7.0, 95

  11. FAILURE OF RADIOACTIVE IODINE IN TREATMENT OF HYPERTHYROIDISM

    Science.gov (United States)

    Schneider, David F.; Sonderman, Philip E.; Jones, Michaela F.; Ojomo, Kristin A.; Chen, Herbert; Jaume, Juan C.; Elson, Diane F.; Perlman, Scott B.; Sippel, Rebecca S.

    2015-01-01

    Introduction Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common, and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism. Methods We conducted a retrospective review of patients treated with RAI from 2007–2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p treatment. 53 (71.6%) received additional RAI, 13 (17.6%) received additional RAI followed by surgery, and the remaining 8 (10.8%) were cured after thyroidectomy. The percentage of patients who failed decreased in a step-wise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses treatment (HR 2.55, 95% CI 1.22–5.33, p=0.01) were associated with failure. Conclusions Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients. PMID:25001092

  12. The role of exogenous risk factors of antituberculosis treatment failure.

    Science.gov (United States)

    Lesnic, Evelina; Ustian, Aurelia; Pop, Carmen Monica

    2016-01-01

    The Republic of Moldova reports the highest incidence of tuberculosis and the lowest treatment success rate among European region countries. In most of the patients the antituberculosis treatment failure is correlated with social risk factors (low socio-economical state, epidemiological danger characteristics) and biological factors (young age, male sex, physiological conditions, associated diseases). Clinical factors (advanced forms of tuberculosis, chronic evolution, immune disturbances), therapeutic factors (treatment errors and interruptions, individualized regimens) and administrative factors (drug interruption in supply, suboptimal treatment quality) prevail in regions with defficient in health care delivery. The association of risk factors has a higher impact than the severity of one risk factor. The risk factor assessment is very important before initiation of the treatment, for establishing the plan of risk reduction measures for increasing the success rate. The aim of the study was to determine the impact of exogenous risk factors on antituberculosis treatment failure. The study was conducted on 201 patients with pulmonary tuberculosis and treatment failure and 105 patients with pulmonary tuberculosis who successfully finished the antituberculosis treatment. Selected cases were investigated according national standards. The treatment failure occurred in patients belonging to socially disadvantaged groups, patients with harmful habits (alcohol abuse, drug use, active smoking), patients from infectious clusters. Migration, homelessness and detention releasing imperil the quality of treatment, thus predisposing to the treatment failure. Social, educational support and the substitutive therapy and withdrawal techniques (tobacco, alcohol, psycho-active substances) must be implemented in the high risk groups in order to diminish the risk of treatment failure and to increase the treatment success rate. The study of exogenous risk factors in vulnerable groups

  13. Predictors of Treatment Failure among Adult Antiretroviral Treatment (ART Clients in Bale Zone Hospitals, South Eastern Ethiopia.

    Directory of Open Access Journals (Sweden)

    Demewoz Haile

    Full Text Available Treatment failure defined as progression of disease after initiation of ART or when the anti-HIV medications can't control the infection. One of the major concerns over the rapid scaling up of ART is the emergence and transmission of HIV drug resistant strains at the population level due to treatment failure. This could lead to the failure of basic ART programs. Thus this study aimed to investigate the predictors of treatment failure among adult ART clients in Bale Zone Hospitals, South east Ethiopia.Retrospective cohort study was employed in four hospitals of Bale zone named Goba, Robe, Ginir and Delomena. A total of 4,809 adult ART clients were included in the analysis from these four hospitals. Adherence was measured by pill count method. The Kaplan Meier (KM curve was used to describe the survival time of ART patients without treatment failure. Bivariate and multivariable Cox proportional hazards regression models were used for identifying associated factors of treatment failure.The incidence rate of treatment failure was found 9.38 (95% CI 7.79-11.30 per 1000 person years. Male ART clients were more likely to experience treatment failure as compared to females [AHR = 4.49; 95% CI: (2.61-7.73].Similarly, lower CD4 count (<100 m3/dl at initiation of ART was found significantly associated with higher odds of treatment failure [AHR = 3.79; 95% CI: (2.46-5.84.Bedridden [AHR = 5.02; 95% CI: (1.98-12.73] and ambulatory [AHR = 2.12; 95% CI: (1.08-4.07] patients were more likely to experience treatment failure as compared to patients with working functional status. TB co-infected clients had also higher odds to experience treatment failure [AHR = 3.06; 95% CI: (1.72-5.44]. Those patients who had developed TB after ART initiation had higher odds to experience treatment failure as compared to their counter parts [AHR = 4.35; 95% CI: (1.99-9.54]. Having other opportunistic infection during ART initiation was also associated with higher odds of

  14. Renal failure after treatment with interferon alpha 2b

    NARCIS (Netherlands)

    Roeloffzen, WWH; Hospers, GAP; De Vries, EGE; Navis, GJ

    2002-01-01

    Although there has been considerable experience with interferons in the treatment of malignancy and viral illnesses, acute renal failure as a side-effect of interferon treatment has rarely been reported. We present the case of a patient who developed acute on chronic renal failure 16 months after

  15. B-type natriuretic peptide-guided treatment for heart failure

    Science.gov (United States)

    McLellan, Julie; Heneghan, Carl J; Perera, Rafael; Clements, Alison M; Glasziou, Paul P; Kearley, Karen E; Pidduck, Nicola; Roberts, Nia W; Tyndel, Sally; Wright, F Lucy; Bankhead, Clare

    2016-01-01

    Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B-type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. Objectives To assess whether treatment guided by serial BNP or NT-proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Search methods Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. Selection criteria We included randomised controlled trials of NP-guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow-up. Adults treated for heart failure, in both in-hospital and out-of-hospital settings, and trials reporting a

  16. Biofeedback in the treatment of heart failure.

    Science.gov (United States)

    McKee, Michael G; Moravec, Christine S

    2010-07-01

    Biofeedback training can be used to reduce activation of the sympathetic nervous system (SNS) and increase activation of the parasympathetic nervous system (PNS). It is well established that hyperactivation of the SNS contributes to disease progression in chronic heart failure. It has been postulated that underactivation of the PNS may also play a role in heart failure pathophysiology. In addition to autonomic imbalance, a chronic inflammatory process is now recognized as being involved in heart failure progression, and recent work has established that activation of the inflammatory process may be attenuated by vagal nerve stimulation. By interfering with both autonomic imbalance and the inflammatory process, biofeedback-assisted stress management may be an effective treatment for patients with heart failure by improving clinical status and quality of life. Recent studies have suggested that biofeedback and stress management have a positive impact in patients with chronic heart failure, and patients with higher perceived control over their disease have been shown to have better quality of life. Our ongoing study of biofeedback-assisted stress management in the treatment of end-stage heart failure will also examine biologic end points in treated patients at the time of heart transplant, in order to assess the effects of biofeedback training on the cellular and molecular components of the failing heart. We hypothesize that the effects of biofeedback training will extend to remodeling the failing human heart, in addition to improving quality of life.

  17. Failure Rate of Pediatric Dental Treatment under General Anesthesia

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    Effat Khodadadi

    2018-06-01

    Full Text Available Aim: To assess the failure rates of various pediatric dental treatments performed under general anesthesia (GA after six months to five years of follow-up. Design: This multicenter retrospective cohort study was performed on patients treated by five pedodontists in two private hospitals located in northern Iran during 2010–2013 and comprised 155 patients. The patients were recalled and clinically examined. During the clinical examination of the primary teeth, oral hygiene, dmft index, and failure of previous treatments was evaluated. The data were analyzed using the Chi square and regression analyses with a significance level of 0.05. Results: 114 patients (74 males and 40 females, mean age: 37.17 ± 10.75 months with 1155 primary teeth treated under GA participated in the follow-up. The overall failure rate was 6.59%. The failure rates of pulpectomy, pulopotomy, fissure sealant, stainless steel crown (SSC, amalgam, and composite fillings were 2.90%, 3.03%, 4.83%, 5.26%, 5.33%, and 9.63%, respectively. Among the confounding factors, only gender had a significant effect on the anterior composite failure rate (p = 0.029 and age had a significant effect on the failure rate of fissure sealant therapy (p = 0.015 and SSC (p = 0.018. Conclusion: The overall rate of treatment failure in pediatric patients, treated under GA, was 6.59%.

  18. Failure of radioactive iodine in the treatment of hyperthyroidism.

    Science.gov (United States)

    Schneider, David F; Sonderman, Philip E; Jones, Michaela F; Ojomo, Kristin A; Chen, Herbert; Jaume, Juan C; Elson, Diane F; Perlman, Scott B; Sippel, Rebecca S

    2014-12-01

    Persistent or recurrent hyperthyroidism after treatment with radioactive iodine (RAI) is common and many patients require either additional doses or surgery before they are cured. The purpose of this study was to identify patterns and predictors of failure of RAI in patients with hyperthyroidism. We conducted a retrospective review of patients treated with RAI from 2007 to 2010. Failure of RAI was defined as receipt of additional dose(s) and/or total thyroidectomy. Using a Cox proportional hazards model, we conducted univariate analysis to identify factors associated with failure of RAI. A final multivariate model was then constructed with significant (p treatment, 53 (71.6 %) received additional RAI, 13 (17.6 %) received additional RAI followed by surgery, and the remaining 8 (10.8 %) were cured after thyroidectomy. The percentage of patients who failed decreased in a stepwise fashion as RAI dose increased. Similarly, the incidence of failure increased as the presenting T3 level increased. Sensitivity analysis revealed that RAI doses treatment (HR 2.55; 95 % CI 1.22-5.33; p = 0.01) were associated with failure. Laboratory values at presentation can predict which patients with hyperthyroidism are at risk for failing RAI treatment. Higher doses of RAI or surgical referral may prevent the need for repeat RAI in selected patients.

  19. Clinical indicators for success of misoprostol treatment after early pregnancy failure.

    Science.gov (United States)

    Robledo, C; Zhang, J; Troendle, J; Barnhart, K; Creinin, M D; Westhoff, C; Huang, X; Frederick, M

    2007-10-01

    To identify clinical indicators for success of misoprostol treatment after early pregnancy failure. A total of 473 women with early pregnancy failure received 800 microg of vaginal misoprostol on treatment day 1. At the follow-up visit on day 3, a second dose was given if expulsion was incomplete. On day 8, vacuum aspiration was offered if expulsion had not occurred. Ultrasonography was used as gold standard for success. A Classification and Regression Tree analysis was undertaken to derive two decision trees for the success of misoprostol treatment on study days 3 and 8. Heavy bleeding after the first dose and an open cervical os were identified as clinical indicators of treatment success on day 3. Treatment success occurred in 84% of women with either or both indicators. Reporting passage of tissue after a second misoprostol dose and old blood in the vagina were potential indicators of treatment success or failure on day 8. A woman with either of these indicators has a 65% chance of treatment success after the second dose. Conversely, a woman with neither indicator on day 8 has a 94% chance of treatment failure. Standard clinical findings may be useful as indicators for success or failure of medical management of early pregnancy failure in settings with limited or no access to ultrasonography. More research to identify even better indicators is warranted.

  20. Clinical features and treatment of organ failure in severe acute pancreatitis

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    CUI Lijian

    2014-08-01

    Full Text Available Organ failure is an important factor causing death in patients with severe acute pancreatitis (SAP. In recent years, thanks to the further study of pathophysiology of SAP and the continuous accumulation of experience and technology, substantial progress has been made in the diagnosis and treatment of SAP complicated by organ failure. The clinical features of SAP complicated by organ failure and the measures to be strengthened in the treatment of SAP are summarized. Currently, it is thought that organ failure tends to appear once SAP occurs, so timely, standardized treatment can shorten the course of disease and significantly reduce mortality.

  1. Clinical Investigation of Treatment Failure in Type 2 Diabetic ...

    African Journals Online (AJOL)

    Clinical Investigation of Treatment Failure in Type 2 Diabetic Patients ... Purpose: To examine body mass index (BMI), occupation, sex, age, and ... development of secondary failure in type 2 diabetics receiving metformin and glibenclamide.

  2. Staff and consumer perspectives on defining treatment success and failure in assertive community treatment.

    Science.gov (United States)

    Stull, Laura G; McGrew, John H; Salyers, Michelle P

    2010-09-01

    Although assertive community treatment (ACT) has been consistently recognized as effective, there has been little research as to what constitutes success in ACT. The purpose of this study was to understand how ACT consumers and staff define treatment success and failure and to examine whether definitions varied between staff and consumers. Investigators conducted semistructured interviews with 25 staff and 23 consumers from four ACT teams. Across perspectives, success and failure were most clearly related to consumer factors. Other themes included having basic needs met, being socially involved, and taking medications. Reduced hospitalizations were mentioned infrequently. Consumers were more likely than staff to identify the level or type of treatment as defining success and failure, whereas staff were more likely than consumers to discuss substance abuse when defining failure and improved symptoms when defining success. Success in ACT should be viewed more broadly than reduced hospitalizations and include domains such as social involvement.

  3. In Vivo Efficacy of Artesunate/Sulphadoxine-Pyrimethamine versus Artesunate/Amodiaquine in the Treatment of Uncomplicated P. falciparium Malaria in Children around the Slope of Mount Cameroon: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Tobias O. Apinjoh

    2016-02-01

    Full Text Available Background: The development and spread of antimalarial drug resistant parasites contributes to the global impact of the disease. In vivo efficacy assessments of treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. Artemisinin-based combinations have been adopted as the first-line treatment for uncomplicated P. falciparum malaria in Cameroon since 2004. Methods: A total of 177 children aged six-months to 10 years with uncomplicated mono-infected falciparum malaria were randomized (1:1 to receive artesunate/sulphadoxine-pyrimethamine (AS/SP or artesunate/amodiaquine (AS/AQ pediatric tablets and followed up for 28 days according to the standard World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response (ACPR on day 28. Results: The PCR corrected cure rate was high, overall (88.1%, 95% CI 83.1–93.1, 85.9% (95% CI 78.2–93.6, and 90.2% (95% CI 83.8–96.6 for AS/SP and AS/AQ, respectively. Twenty-one treatment failures were observed during follow-up, constituting one (4.6%, 14 (8.2%, and six (3.5% early treatment failure (ETF, late clinical failure (LCF, and late parasitological failure (LPF, respectively. The drugs were well tolerated with no serious adverse events. Conclusions: Both AS/SP and AS/AQ are highly effective and well-tolerated treatments for uncomplicated P. falciparum malaria around the slope of Mount Cameroon.

  4. Endocavitary in vivo Dosimetry for IMRT Treatments of Gynecologic Tumors

    International Nuclear Information System (INIS)

    Cilla, Savino; Macchia, Gabriella; Digesù, Cinzia; Deodato, Francesco; Sabatino, Domenico; Morganti, Alessio G.; Piermattei, Angelo

    2011-01-01

    The accuracy and reproducibility of endometrial carcinoma treatment with intensity-modulated radiotherapy (IMRT) was assessed by means of in vivo dosimetry. Six patients who had previously undergone radical hysterectomy for endometrial carcinoma were treated with IMRT using a vaginal applicator with radio-opaque fiducial markers. An ion-chamber inserted into the applicator supplied an endocavitary in vivo dosimetry for quality assurance purposes. The ratio R = D/D TPS between the in vivo measured dose D and the predicted dose by the treatment planning system D TPS was determined for every fraction of the treatment. Results showed that 90% and 100% of the ratios resulted equal to 1 within 5% and 10%, respectively. The mean value of the ratios distribution for the 6 patients was R = 0.995 and the SD = 0.034. The ratio R* between the measured and predicted total doses for each patient was near to 1, within 2%. The dosimetric results suggest that the use of a vaginal applicator in an image-guided approach could make the interfractions target position stable and reproducible, allowing a safe use of the IMRT technique in the treatment of postoperative vaginal vault. In vivo dosimetry may supply useful information about the discrimination of random vs. systematic errors. The workload is minimum and this in vivo dosimetry can be applied also in the clinical routine.

  5. Outcome and treatment of postoperative spine surgical site infections: predictors of treatment success and failure.

    Science.gov (United States)

    Maruo, Keishi; Berven, Sigurd H

    2014-05-01

    Surgical site infection (SSI) is an important complication after spine surgery. The management of SSI is characterized by significant variability, and there is little guidance regarding an evidence-based approach. The objective of this study was to identify risk factors associated with treatment failure of SSI after spine surgery. A total of 225 consecutive patients with SSI after spine surgery between July 2005 and July 2010 were studied retrospectively. Patients were treated with aggressive surgical debridement and prolonged antibiotic therapy. Outcome and risk factors were analyzed in 197 patients having 1 year of follow-up. Treatment success was defined as resolution within 90 days. A total of 126 (76 %) cases were treated with retention of implants. Forty-three (22 %) cases had treatment failure with five (2.5 %) cases resulting in death. Lower rates of treatment success were observed with late infection (38 %), fusion with fixation to the ilium (67 %), Propionibacterium acnes (43 %), poly microbial infection (68 %), >6 operated spinal levels (67 %), and instrumented cases (73 %). Higher rates of early resolution were observed with superficial infection (93 %), methicillin-sensitive Staphylococcus aureus (95 %), and failure. Superficial infection and methicillin-sensitive Staphylococcus aureus were predictors of early resolution. Postoperative spine infections were treated with aggressive surgical debridement and antibiotic therapy. High rates of treatment failure occurred in cases with late infection, long instrumented fusions, polymicrobial infections, and Propionibacterium acnes. Removal of implants and direct or staged re-implantation may be a useful strategy in cases with high risk of treatment failure.

  6. Risk factors for treatment failure and recurrence of anisometropic amblyopia.

    Science.gov (United States)

    Kirandi, Ece Uzun; Akar, Serpil; Gokyigit, Birsen; Onmez, Funda Ebru Aksoy; Oto, Sibel

    2017-08-01

    The aim of this study was to identify factors associated with failed vision improvement and recurrence following occlusion therapy for anisometropic amblyopia in children aged 7-9 years. We retrospectively reviewed the medical records of 64 children aged 7-9 years who had been diagnosed as having anisometropic amblyopia and were treated with patching. Functional treatment failure was defined as final visual acuity in the amblyopic eye of worse than 20/32. Improvement of fewer than two logMAR lines was considered relative treatment failure. Recurrence was defined as the reduction of at least two logMAR levels of visual acuity after decreased or discontinued patching. Functional and relative success rates were 51.6 and 62.5 %, respectively. The most important factor for functional treatment failure [adjusted odds ratio (OR) (95 % confidence interval, CI) 11.57 (1.4-95.74)] and the only risk factor for recurrence [adjusted OR (95 % CI) 3.04 (1.13-8.12)] were the same: high spherical equivalent (SE) of the amblyopic eye. A large interocular difference in the best-corrected visual acuity was found to be a risk factor for both functional and relative failure. High SE of the amblyopic eye was the most influential risk factor for treatment failure and recurrence in compliant children aged 7-9 years.

  7. Predictors of treatment failure for pneumatic retinopexy.

    Science.gov (United States)

    Rootman, Dan B; Luu, Shelly; M Conti, Stephen; Mandell, Mark; Devenyi, Robert; Lam, Wai-Ching; Kertes, Peter J

    2013-12-01

    The purpose of this study was to define the overall anatomic success rate in pneumatic retinopexy and to identify morphologic features that may be predictive of treatment failure in pneumatic retinopexy. Prospective consecutive interventional case series of patients with new-onset primary rhegmatogenous retinal detachments treated with pneumatic retinopexy. In this interventional case series, consecutive patients with new-onset primary rhegmatogenous retinal detachments were treated with pneumatic retinopexy and followed prospectively. Morphologic data were collected on 3-colour fundus drawings. The primary outcome measure was treatment failure, defined as requirement for scleral buckle or vitrectomy within the follow-up period. Rates of failure for each morphologic feature were compared and a logistic regression model was fit. A total of 113 eyes were included in the study. Anatomic success was achieved in 69.6% of patients. Morphologic criteria including the position and number of breaks, position and extent of lattice degeneration, size of the detached area, and macular status were all found not to be significantly related to failure. In multivariate analysis, only 3 predictors, pseudophakic status (p < 0.05, odds ratio [OR] 2.9, 95% CI, 1.06-7.88), presence of retinal break greater than 1 clock-hour (p < 0.05, OR 3.41, 1.06-11.02), and presence of grade C or D proliferative vitreoretinopathy (PVR) (p < 0.01, OR 31.83, 95% CI, 3.59-282.24), gained statistical significance. Only pseudophakia, a large retinal break, and/or PVR was associated with an increased likelihood of failure. Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

  8. Intravenous Milrinone in Treatment of Advanced Congestive Heart Failure

    Science.gov (United States)

    Zewail, Aly M.; Nawar, Mohammad; Vrtovec, Bojan; Eastwood, Cathy; Kar, Biswajit; Delgado, Reynolds M.

    2003-01-01

    Phosphodiesterase inhibitors such as milrinone can relieve symptoms and improve hemodynamics in patients with advanced congestive heart failure. We retrospectively evaluated the hemodynamic and clinical outcomes of long-term combination therapy with intravenous milrinone and oral β-blockers in 65 patients with severe congestive heart failure (New York Heart Association class IV function and ejection fraction milrinone. Oral medical therapy was maximized when possible. The mean duration of milrinone treatment in this combination-treatment group was 269 days (range, 14–1,026 days). Functional class improved from IV to II–III with milrinone therapy. Twenty-four such patients tolerated β-blocker up-titration and were successfully weaned from milrinone. Sixteen patients (31%) died while receiving combination therapy; one died of sudden cardiac death (on treatment day 116); the other 15 died of progressive heart failure or other complications. Hospital admissions during the previous 6 months and admissions within 6 months after milrinone initiation stayed the same. Meanwhile, the total number of hospital days decreased from 450 to 380 (a 15.6% reduction), and the mean length of stay decreased by 1.4 days (a 14.7% reduction). We conclude that 1) milrinone plus β-blocker combination therapy is an effective treatment for heart failure even with β-blocker up-titration, 2) weaning from milrinone may be possible once medications are maximized, 3) patients' functional status improves on the combination regimen, and 4) treatment-related sudden death is relatively infrequent during the combination regimen. (Tex Heart Inst J 2003;30:109–13) PMID:12809251

  9. Factors Predicting Treatment Failure in Patients Treated with Iodine-131 for Graves’ Disease

    International Nuclear Information System (INIS)

    Manohar, Kuruva; Mittal, Bhagwant Rai; Bhoil, Amit; Bhattacharya, Anish; Dutta, Pinaki; Bhansali, Anil

    2013-01-01

    Treatment of Graves' disease with iodine-131 ( 131 I) is well-known; however, all patients do not respond to a single dose of 131 I and may require higher and repeated doses. This study was carried out to identify the factors, which can predict treatment failure to a single dose of 131 I treatment in these patients. Data of 150 patients with Graves' disease treated with 259-370 MBq of 131 I followed-up for at least 1-year were retrospectively analyzed. Logistic regression analysis was used to predict factors which can predict treatment failure, such as age, sex, duration of disease, grade of goiter, duration of treatment with anti-thyroid drugs, mean dosage of anti-thyroid drugs used, 99m Tc-pertechnetate ( 99m TcO 4 - ) uptake at 20 min, dose of 131 I administered, total triiodothyronine and thyroxine levels. Of the 150 patients, 25 patients required retreatment within 1 year of initial treatment with 131 I. Logistic regression analysis revealed that male sex and 99m TcO 4 - uptake were associated with treatment failure. On receiver operating characteristic (ROC) curve analysis, area under the curve (AUC) was significant for 99m TcO 4 - uptake predicting treatment failure (AUC = 0.623; P = 0.039). Optimum cutoff for 99m TcO 4 - uptake was 17.75 with a sensitivity of 68% and specificity of 66% to predict treatment failure. Patients with >17.75% 99m TcO 4 - uptake had odds ratio of 3.14 (P = 0.014) for treatment failure and male patients had odds ratio of 1.783 for treatment failure. Our results suggest that male patients and patients with high pre-treatment 99m TcO 4 - uptake are more likely to require repeated doses of 131 I to achieve complete remission

  10. Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

    Science.gov (United States)

    Haffner, D; Schaefer, F; Nissel, R; Wühl, E; Tönshoff, B; Mehls, O

    2000-09-28

    Growth hormone treatment stimulates growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. We followed 38 initially prepubertal children with chronic renal failure treated with growth hormone for a mean of 5.3 years until they reached their final adult height. The mean (+/-SD) age at the start of treatment was 10.4+/-2.2 years, the mean bone age was 7.1+/-2.3 years, and the mean height was 3.1+/-1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with growth hormone served as controls. The children treated with growth hormone had sustained catch-up growth, whereas the control children had progressive growth failure. The mean final height of the growth hormone-treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the growth hormone-treated children was 1.6+/-1.2 SD below normal, which was 1.4 SD above their standardized height at base line (Pgrowth hormone-treated children, treatment was not associated with a shortening of the pubertal growth spurt. The total height gain was positively associated with the initial target-height deficit and the duration of growth hormone therapy and was negatively associated with the percentage of the observation period spent receiving dialysis treatment. Long-term growth hormone treatment of children with chronic renal failure induces persistent catch-up growth, and the majority of patients achieve normal adult height.

  11. Apicotomy as Treatment for Failure of Orthodontic Traction

    Directory of Open Access Journals (Sweden)

    Leandro Berni Osório

    2013-01-01

    Full Text Available Objective. The purpose of this study was to present a case report that demonstrated primary failure in a tooth traction that was subsequently treated with apicotomy technique. Case Report. A 10-year-old girl had an impacted upper right canine with increased pericoronal space, which was apparent on a radiographic image. The right maxillary sinus showed an opacity suggesting sinusitis. The presumptive diagnosis was dentigerous cyst associated with maxillary sinus infection. The plan for treatment included treatment of the sinus infection and cystic lesion and orthodontic traction of the canine after surgical exposure and bonding of an orthodontic appliance. The surgical procedure, canine position, root dilaceration, and probably apical ankylosis acted in the primary failure of the orthodontic traction. Surgical apical cut of the displaced teeth was performed, and tooth position in the dental arch was possible, with a positive response to the pulp vitality test. Conclusion. Apicotomy is an effective technique to treat severe canine displacement and primary orthodontic traction failure of palatally displaced canines.

  12. In vivo tracking of magnetically labeled mesenchmal stem cells injected via renal arteries in kidney failure rat

    International Nuclear Information System (INIS)

    Sun Junhui; Teng Gaojun; Ju Shenghong; Ma Zhanlong; Mai Xiaoli; Zhang Yu; Ma Ming

    2006-01-01

    Objective: To evaluate in vivo depiction and tracking for magnetically labeled bone marrow mesenchymal stern cells (MSCs) in a renal failure rat model injected intravascularly using a 1.5 T magnetic resonance imaging (MRI) system. Methods: Rat MSCs were isolated, purified, expanded and then incubated with home synthesized Fe 2 O 3 -PLL. Prussian blue stain was employed for identifying intracellular irons. An acute renal failure in rat was induced by intramuscular injection of glycerol and MSCs were injected into renal arteries of 11 recipients (labeled cells in six, unlabeled cells in five). MR images of kidneys were obtained respectively before injection of MSCs, and immediately, 1, 3, 5, and 8 clays after transplantation. MR imaging findings were analyzed, which were correlated with histological findings. Results: Rat MSCs were successfully labeled, and labeling efficiency was almost 100%. Prussian blue staining of Fe 2 O 3 -PLL labeled cells revealed the presence of iron-containing vesicles or endosomes in the cytoplasm. In the renal failure model of rats, the labeled MSCs were demonstrated as signal intensity loss in renal cortex on T 2 * -weighted MR images. The signal intensity decrease was visualized up to days 8 after transplantation. Histological analyses showed that most Prussian blue staining-positive cells were well correlated with the area where a signal intensity loss was observed in MRI. Signal intensity decrease was not detected after transplantation of unlabeled cells. Conclusion: The rat MSCs can be effectively labeled with Fe 2 O 3 -PLL. 1.5-T MR imaging seems to be a good technique to monitor the magnetically labeled MSCs in vivo in renal failure rat model intravascularly administered, which may have much more potential values for studying the engraftment of stem cells in kidneys. (authors)

  13. Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method

    Science.gov (United States)

    White, Richard A.; Lu, Chunling; Rodriguez, Carly A.; Bayona, Jaime; Becerra, Mercedes C.; Burgos, Marcos; Centis, Rosella; Cohen, Theodore; Cox, Helen; D'Ambrosio, Lia; Danilovitz, Manfred; Falzon, Dennis; Gelmanova, Irina Y.; Gler, Maria T.; Grinsdale, Jennifer A.; Holtz, Timothy H.; Keshavjee, Salmaan; Leimane, Vaira; Menzies, Dick; Milstein, Meredith B.; Mishustin, Sergey P.; Pagano, Marcello; Quelapio, Maria I.; Shean, Karen; Shin, Sonya S.; Tolman, Arielle W.; van der Walt, Martha L.; Van Deun, Armand; Viiklepp, Piret

    2016-01-01

    Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection. We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference. Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34–0.42) for all patients and 0.33 (0.25–0.42) for HIV-co-infected patients. Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests. PMID:27587552

  14. Stem Cells Transplantation in the Treatment of Patients with Liver Failure.

    Science.gov (United States)

    Tao, Ya-Chao; Wang, Meng-Lan; Chen, En-Qiang; Tang, Hong

    2018-02-23

    Liver failure is a life-threatening liver disease encompassing severe acute deterioration of liver function. Emergency liver transplantation is the only curative treatment for liver failure, but is restricted by the severe shortage of organ donors. Stem cell, including embroyonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells and hepatic progenitor cells, have capacity to proliferate and differentiate and could be used in a variety of liver diseases including hereditary liver diseases, cirrhosis and liver failure. We summarized the basic experimental and clinical advances of stem cell transplantation in liver failure treatment, and also discussed the advantages and disadvantage of different stem cells subtype in this field, aiming to provide a perspective on the stem cell-based therapy for liver failure. Stem cells, especially mesenchymal stem cells (mainly low immunogenicity and paracrine characteristics) and induced pluripotent stem cells (generation of desired cell type from somatic cell), are feasible candidates for cell therapy in the treatment of liver failure, but there are some drawbacks remaining to be resolved, such as low engraftment, cryotpreservation methods and tumorigenesis. Stem cell transplantation is a promising but challenging strategy and paves a new way for curing liver failure. But more efforts need to be made to overcome problems before this new strategy could be safely and effectively applied to humans. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. [Treatment of intestinal failure in adults. I. Dietary measures

    NARCIS (Netherlands)

    Wanten, G.J.A.; Sauerwein, H.P.; Broek, P. van den; Kristinsson, J.O.

    2007-01-01

    Patients with intestinal failure, predominantly caused by short-bowel syndrome, have impaired quality of life due to the frequent development of complications. Dietary modifications have an established role in the treatment of short-bowel syndrome. Treatment of short-bowel syndrome includes

  16. Bioartificial liver and liver transplantation: new modalities for the treatment of liver failure

    Directory of Open Access Journals (Sweden)

    DING Yitao

    2017-09-01

    Full Text Available The main features of liver failure are extensive necrosis of hepatocytes, rapid disease progression, and poor prognosis, and at present, there are no effective drugs and methods for the treatment of liver failure. This article summarizes four treatment methods for liver failure, i.e., medical treatment, cell transplantation, liver transplantation, and artificial liver support therapy, and elaborates on the existing treatment methods. The current medical treatment regimen should be optimized; cell transplantation has not been used in clinical practice; liver transplantation is the most effective method, but it is limited by donor liver shortage and high costs; artificial liver can effectively remove toxic substances in human body. Therefore, this article puts forward artificial liver as a transition for liver transplantation; artificial liver can buy time for liver regeneration or liver transplantation and prolong patients′ survival time and thus has a promising future. The new treatment modality of bioartificial liver combined with liver transplantation may bring good news to patients with liver failure.

  17. Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

    Science.gov (United States)

    Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A.

    2017-01-01

    Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general. PMID:26514749

  18. Management of growth failure in the treatment of malignant disease

    International Nuclear Information System (INIS)

    Leiper, A.D.

    1990-01-01

    Growth failure due to endocrine dysfunction as a result of treatment for malignant disease is becoming increasingly common. It may occur after cranial or craniospinal irradiation given in the treatment of acute lymphoblastic leukemia and brain tumors, and is often coupled with early or precocious puberty. It also occurs after neck and gonadal radiation and is particularly severe after total body irradiation where multiple endocrine deficiencies frequently occur. Failure to appreciate its occurrence or failure to institute therapy early enough may lead to short stature in adult life. Accurate and regular monitoring of standing and sitting height, bone age, and endocrine data should be undertaken by the oncologist in close collaboration with an endocrinologist, to ensure appropriate management of the patient. 17 references

  19. Azithromycin Treatment Failure for Chlamydia trachomatis Among Heterosexual Men With Nongonococcal Urethritis.

    Science.gov (United States)

    Kissinger, Patricia J; White, Scott; Manhart, Lisa E; Schwebke, Jane; Taylor, Stephanie N; Mena, Leandro; Khosropour, Christine M; Wilcox, Larissa; Schmidt, Norine; Martin, David H

    2016-10-01

    Three recent prospective studies have suggested that the 1-g dose of azithromycin for Chlamydia trachomatis (Ct) was less effective than expected, reporting a wide range of treatment failure rates (5.8%-22.6%). Reasons for the disparate results could be attributed to geographic or methodological differences. The purpose of this study was to reexamine the studies and attempt to harmonize methodologies to reduce misclassification as a result of false positives from early test-of-cure (TOC) or reinfection as a result of sexual exposure rather than treatment failure. Men who had sex with women, who received 1-g azithromycin under directly observed therapy for presumptive treatment of nongonococcal urethritis with confirmed Ct were included. Baseline screening was performed on urethral swabs or urine, and TOC screening was performed on urine using nucleic acid amplification tests. Posttreatment vaginal sexual exposure was elicited at TOC. Data from the 3 studies were obtained and reanalyzed. Rates of Ct retest positive were examined for all cases, and a sensitivity analysis was conducted to either reclassify potential false positives/reinfections as negative or remove them from the analysis. The crude treatment failure rate was 12.8% (31/242). The rate when potential false positives/reinfections were reclassified as negative was 6.2% (15/242) or when these were excluded from analysis was 10.9% (15/138). In these samples of men who have sex with women with Ct-related nongonococcal urethritis, azithromycin treatment failure was between 6.2% and 12.8%. This range of failure is lower than previously published but higher than the desired World Health Organization's target chlamydia treatment failure rate of < 5%.

  20. Erythropoietin treatment does not compromise cardiovascular function in chronic renal failure

    DEFF Research Database (Denmark)

    Haedersdal, C; Mehlsen, J; Stenver, Doris Irene

    1994-01-01

    The anemia in patients with chronic renal failure can be corrected through treatment with recombinant human erythropoietin treatment. This correction is associated with changes in the rheologic variables, which could explain the changes in hemodynamics found by many investigators. The authors have...... followed up 11 patients with chronic renal failure on hemodialysis before and during six months of therapy with erythropoietin. The measurements were made before treatment, after four months of therapy, and after six months of therapy. The measurements included hematocrit, osmotic resistance of the red...

  1. Patient Characteristics, Health Care Resource Utilization, and Costs Associated with Treatment-Regimen Failure with Biologics in the Treatment of Psoriasis.

    Science.gov (United States)

    Foster, Shonda A; Zhu, Baojin; Guo, Jiaying; Nikai, Enkeleida; Ojeh, Clement; Malatestinic, William; Goldblum, Orin; Kornberg, Lori J; Wu, Jashin J

    2016-04-01

    Psoriasis is a chronic, incurable, and immune-mediated skin disorder that is characterized by erythematous scaly papules and plaques. Understanding of psoriasis at the molecular level has led to the development of biologic agents that target disease-specific inflammatory mediators in psoriatic lesions. Biologic agents have become important components of the psoriasis armamentarium, but some patients become refractory to these agents over time or fail to respond to subsequent biologics. To (a) evaluate demographic and clinical characteristics of psoriasis patients who have treatment patterns suggestive of failure to a newly initiated biologic agent (treatment-regimen failures) compared with those who do not (non-treatment-regimen failures) and (b) to assess health care-related resource utilization and costs in non-treatment-regimen failures and treatment-regimen failures. In this retrospective observational cohort study, patients were selected from the MarketScan claims database of commercially insured individuals and individuals with Medicare supplemental insurance. The index event was a newly initiated biologic agent for the treatment of psoriasis (etanercept, adalimumab, ustekinumab, or infliximab) between January 2010 and December 2011. The analysis included psoriasis patients aged ≥ 18 years with ≥ 1 prescription claim for a biologic and continuous enrollment 12 months pre- and post-index date. Patients with claims for a biologic in the pre-index period were excluded. Patients were divided into treatment-regimen-failure and non-treatment-regimen-failure groups based on their treatment patterns post-index date. The treatment-regimen-failure group included patients who switched to another biologic, discontinued the biologic without restarting, increased the dose of the biologic, or augmented treatment with a nontopical psoriasis medication during the post-index period. Between-group patient characteristics and medication use were compared using analysis of

  2. Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease.

    Science.gov (United States)

    Kuo, Ho-Chang; Liang, Chi-Di; Wang, Chih-Lu; Yu, Hong-Ren; Hwang, Kao-Pin; Yang, Kuender D

    2010-10-01

    Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are initial IVIG treatment. This study was conducted to investigate the risk factors for initial IVIG treatment failure in KD. Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients were divided into IVIG-responsive and IVIG-resistant groups. Initial laboratory data before IVIG treatment were collected for analysis. A total of 131 patients were enrolled during the study period. At 48 h after completion of initial IVIG treatment, 20 patients (15.3%) had an elevated body temperature. Univariate analysis showed that patients who had initial findings of high neutrophil count, abnormal liver function, low serum albumin level (≤2.9 g/dL) and pericardial effusion were at risk for IVIG treatment failure. Multivariate analysis with a logistic regression procedure showed that serum albumin level was considered the independent predicting factor of IVIG resistance in patients with KD (p = 0.006, OR = 40, 95% CI: 52.8-562). There was no significant correlation between age, gender, fever duration before IVIG treatment, haemoglobin level, total leucocyte and platelet counts, C-reactive protein level, or sterile pyuria and initial IVIG treatment failure. The specificity and sensitivity for prediction of IVIG treatment failure in this study were 96% and 34%, respectively. Pre-IVIG treatment serum albumin levels are a useful predictor of IVIG resistance in patients with KD. © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.

  3. Recovery following Thyroxine Treatment Withdrawal, but Not Propylthiouracil, Averts In Vivo and Ex Vivo Thyroxine-Provoked Cardiac Complications in Adult FVB/N Mice

    Directory of Open Access Journals (Sweden)

    Nancy S. Saad

    2017-01-01

    Full Text Available Persistent cardiovascular pathology has been described in hyperthyroid patients even with effective antithyroid treatment. Here, we studied the effect of a well-known antithyroid drug, propylthiouracil (PTU; 20 mg/kg/day, on thyroxine (T4; 500 µg/kg/day-induced increase in blood pressure (BP, cardiac hypertrophy, and altered responses of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment. Furthermore, the potential recovery through 2 weeks of T4 treatment discontinuation was also investigated. PTU and T4 recovery partially reduced the T4-prompted increase in BP. Alternatively, PTU significantly improved the in vivo left ventricular (LV function with no considerable effects on cardiac hypertrophy or ex vivo right ventricular (RV contractile alterations subsequent to T4 treatment. Conversely, T4 recovery considerably enhanced the T4-provoked cardiac changes both in vivo and ex vivo. Altogether, our data is in agreement with the proposal that hyperthyroidism-induced cardiovascular pathology could persevere even with antithyroid treatments, such as PTU. However, this cannot be generalized and further investigation with different antithyroid treatments should be executed. Moreover, we reveal that recovery following experimental hyperthyroidism could potentially ameliorate cardiac function and decrease the risk for additional cardiac complications, yet, this appears to be model-dependent and should be cautiously construed.

  4. Addressing the Challenges of Hepatitis C Virus Resistance and Treatment Failure

    Directory of Open Access Journals (Sweden)

    Che C. Colpitts

    2016-08-01

    Full Text Available Chronic hepatitis C is a major cause of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The development of direct-acting antivirals (DAAs revolutionized hepatitis C virus (HCV treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. While antiviral resistance is a significant limitation for interferon-based therapies, resistance and treatment failure still appear to be present in a small fraction of patients even in state-of-the-art DAA combination therapies. Therefore, treatment failure and resistance still remain a clinical challenge for the management of patients not responding to DAAs. In this special issue of Viruses on HCV drug resistance, mechanisms of antiviral resistance for different classes of antiviral drugs are described. Furthermore, the detection and monitoring of resistance in clinical practice, the clinical impact of resistance in different patient groups and strategies to prevent and address resistance and treatment failure using complementary antiviral strategies are reviewed.

  5. Addressing the Challenges of Hepatitis C Virus Resistance and Treatment Failure.

    Science.gov (United States)

    Colpitts, Che C; Baumert, Thomas F

    2016-08-16

    Chronic hepatitis C is a major cause of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The development of direct-acting antivirals (DAAs) revolutionized hepatitis C virus (HCV) treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. While antiviral resistance is a significant limitation for interferon-based therapies, resistance and treatment failure still appear to be present in a small fraction of patients even in state-of-the-art DAA combination therapies. Therefore, treatment failure and resistance still remain a clinical challenge for the management of patients not responding to DAAs. In this special issue of Viruses on HCV drug resistance, mechanisms of antiviral resistance for different classes of antiviral drugs are described. Furthermore, the detection and monitoring of resistance in clinical practice, the clinical impact of resistance in different patient groups and strategies to prevent and address resistance and treatment failure using complementary antiviral strategies are reviewed.

  6. Anxiety and depression after failure of assisted reproductive treatment among patients experiencing infertility.

    Science.gov (United States)

    Maroufizadeh, Saman; Karimi, Elaheh; Vesali, Samira; Omani Samani, Reza

    2015-09-01

    To investigate the impact of the number of previous infertility treatment failures on anxiety and depression. In a cross-sectional study, individuals (men and women, but not couples) aged at least 18 years who had a history of infertility and could read and write in Persian were enrolled at the Royan Institute, Tehran, Iran, between November 1, 2013, and February 28, 2014. Participants provided demographic and infertility information and completed the Persian version of the Hospital Anxiety and Depression Scale (HADS). Overall, 330 patients (122 men, 208 women) were included. Mean scores on the HADS anxiety and depression subscales (HADS-A and HADS-D) were 8.40±4.51 and 5.95±3.54, respectively. In multiple regression analysis, mean HADS-A scores were significantly higher for patients with one treatment failure (9.57±4.58) than for those without a history of treatment (7.79±4.13; P=0.003). HADS-D scores were significantly higher for patients with two failures (6.92±3.69) than for those with no previous treatment (5.59±3.79; P=0.019). Patients with infertility have increased depression and anxiety after infertility treatment failure. Counseling or treatment for these potential psychological effects should be considered after infertility treatment failure. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Ovarian failure due to cancer treatment and fertility preservation options

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam

    2016-04-01

    Full Text Available Primary ovarian insufficiency (POI, commonly referred to premature ovarian failure, is defined as ovarian failure before the age of 40 years. It is the loss of ovarian function caused by a process directly affecting ovaries. Cancer therapy which includes surgery, radiotherapy, and chemotherapy influence ovarian function, leading to premature menopause and loss of fertility. POI is idiopathic in most cases (74-90%. The known causes, in addition to anticancer treatment, are other processes like chromosomal abnormalities, autoimmunity, and natural aging can result in secondary ovarian failure, which is detected by an increase in serum gonadotropin levels (FSH and LH. There are evident risks of POI in women treated for cancer. Those who receive anticancer treatments have an increased risk of developing POI. There by, anticancer drugs and radiation therapy are considered as the most common toxins of ovaries. Although cancer incidence rates in women less than 50 years old continue to increase during recent years, mortality rates are dramatically decreasing due to modern advances in treatment. Increasing numbers of survivors are now confronted with the long-term consequences of exposure to these treatments. The pool of primordial follicles in the ovary is fixed and any injury to the ovary can potentially reduce this ovarian reserve, effectively advancing the patient’s reproductive age, thus narrowing the window of reproductive opportunity. Ovarian failure occurs in a significant percentage of childhood cancer survivors and many of them will seek care for reproductive dysfunction. Nevertheless, Embryo cryopreservation, oocyte cryopreservation, ovary tissue cryopreservation, ovarian suppression and oophoro-pexy are some options to preserve fertility in these groups. As a result, having foreknowledge of potential treatment related ovarian failure will allow the physician to give a better counsel to patients and their family regarding the importance and

  8. Patterns of initial treatment failure of esophageal cancer following radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Sugahara, Shinji; Nakajima, Kotaro [Hitachi General Hospital, Ibaraki (Japan); Ohara, Kiyoshi; Okumura, Toshiyuki; Irie, Toshiyuki; Itai, Yuji

    1999-11-01

    Sixty patients with stage I-III esophageal squamous cell cancer treated by definitive radiotherapy (RT) were analyzed for patterns of treatment failure. Patients were treated by external RT alone (n=45) or in combination with intraluminal RT (N=15) when suitable, with prescribed total doses ranging from 59.4 to 104.4 Gy. Concurrent chemotherapy consisting of cisplatin and/or 5-fluorouracil was administered to 19 patients. The two-year actuarial survival rate and two year disease-free survival rate were 29.5% and 18.3%, respectively. Two-year failure rates were 66.5%, 36.9%, and 3.8%, for the esophagus, lymph nodes, and other sites, respectively. Two-year esophageal failure rates for patients with T1-2 (n=8), T3 (n=30), and T4 disease (n=22) were 14.3%, 64.7%, and 87.9%, respectively (p<0.05). A multivariate analysis of esophageal failure with descriptive variables of T classification, tumor length, and performance of intraluminal RT revealed that only T classification was an independent factor (p=0.021). Two-year lymph node failure rates were 24.8% and 33.6% for patients with N0 (n=36) and N1 disease (n=24), respectively (p=0.0035). Lymph node failure in N0 patients was found exclusively outside the treatment field. These results suggest that inclusion of potential lymph node metastases in the radiation field could lessen the lymph node failure rate in T1-3N0M0 patients. (author)

  9. Trends in antibiotic treatment of acute otitis media and treatment failure in children, 2000-2011.

    Directory of Open Access Journals (Sweden)

    Leah J McGrath

    Full Text Available Guidelines to treat acute otitis media (AOM were published in 2004. Initial declines in prescribing were shown, but it's unknown if they were sustained. We examine trends in antibiotic dispensing patterns to treat AOM among a large population of children. We also document trends in antibiotic failure.Children aged 3 months to 12 years with an AOM diagnosis, enrolled in a commercial claims database between January 1, 2000-December 31, 2011 were included. Pharmacy claims within 7 days of diagnosis were searched for antibiotic prescriptions. Antibiotic failure was defined as a dispensing of a different antibiotic class within 2-18 days after the first prescription. We analyzed trends in antibiotic use and failure by class of antibiotic and year.We identified over 4 million children under 13 years with AOM. The proportion of antibiotic dispensing decreased from 66.0% in 2005 to 51.9% in 2007, after which the instances of dispensing rebounded to pre-guideline levels. However, levels began decreasing again in 2010 and the antibiotic use rate in 2011 was 57.6%. Cephalosporin prescriptions increased by 41.5% over eleven years. Antibiotic failure decreased slightly, and macrolides had the lowest proportion of failures, while all other classes had failure rates around 10%.In recent years, antibiotic dispensing to treat AOM remains high. In addition, the use of broad-spectrum antibiotics is increasing despite having a high rate of treatment failure. Overprescribing of antibiotics and use of non-penicillin therapy for AOM treatment could lead to the development of antibiotic-resistant infections.

  10. Continued efficacy of sulfadoxine-pyrimethamine as second line treatment for malaria in children in Guinea-Bissau

    DEFF Research Database (Denmark)

    Kofoed, Poul-Erik; Rodrigues, Amabelia; Aaby, Peter

    2006-01-01

    BACKGROUND: Sulfadoxine-pyrimethamine (S/P) is widely used for treatment of failures following the first line treatment for malaria in Africa. In Guinea-Bissau, it has been recommended as second line therapy by the National Malaria Programme since 1996. In order to monitor any change of the in vivo...... sensitivity, the efficacy of S/P was studied immediately before the introduction of the drug and 6-9 years later. METHODS: Children participating in clinical in vivo studies were given S/P if having late clinical treatment failure following the treatment with quinine, chloroquine, or amodiaquine...

  11. Accuracy of a Rationally Derived Method for Identifying Treatment Failure in Children and Adolescents

    Science.gov (United States)

    Bishop, Matthew J.; Bybee, Taige S.; Lambert, Michael J.; Burlingame, Gary M.; Wells, M. Gawain; Poppleton, Landon E.

    2005-01-01

    Psychotherapy outcome can be enhanced by early identification of potential treatment failures before they leave treatment. In adults, compelling data are emerging that provide evidence that an early warning system that identifies potential treatment failures can be developed and applied to enhance outcome. The present study reports an analysis of…

  12. Effects of ex-vivo and in-vivo treatment with probiotics on the inflammasome in dogs with chronic enteropathy.

    Directory of Open Access Journals (Sweden)

    Silke Schmitz

    Full Text Available Inflammasomes coordinate the maturation of IL-1β and IL-18 in response to danger signals. They are vital for maintenance of intestinal homeostasis and have been linked to chronic intestinal inflammation in humans. Probiotics have been advocated as treatment in intestinal inflammation. So far, no study has investigated the role of the inflammasome in canine chronic enteropathy (CE. In this study the intestinal expression of inflammasome components was assessed in CE dogs compared to controls, when treated with probiotic Enterococcus faecium (EF ex-vivo and in-vivo. RNA extraction from endoscopic biopsies and reverse-transcriptase quantitative PCR was performed for NLRP3, casp-1, IL-1β and IL-18. Immunohistochemistry was performed to investigate protein expression in tissues. Gene expression of casp-1 and NLRP3 was lower in CE samples than controls. Ex-vivo treatment with EF reduced NLRP3 expression in control samples. Treatment of CE dogs with EF alongside dietary intervention had no effect on gene expression. In contrast, IL-1β protein expression in CE decreased with dietary treatment (but not with probiotics. The results of this study suggest that the inflammasome or its components may be partially involved in the inflammatory process seen in CE, but distinct from intestinal inflammation in humans.

  13. Delineating sites of failure following post-prostatectomy radiation treatment using 68Ga-PSMA-PET.

    Science.gov (United States)

    Byrne, Keelan; Eade, Thomas; Kneebone, Andrew; Guo, Linxin; Hsiao, Ed; Schembri, Geoff; Kwong, Carolyn; Hunter, Julia; Emmett, Louise; Hruby, George

    2018-02-01

    To identify sites of failure with 68 Ga-PSMA-PET (PSMA-PET) imaging in patients who have Biochemical Failure (BF) following post-prostatectomy radiotherapy. Between June 2006 and January 2016, 409 men received post prostatectomy intensity modulated radiation treatment (IMRT) with protocolised planning. 310 patients received radiation treatment (RT) to the Prostate Fossa (PF) alone and 99 patients received RT to PF and pelvic lymphatics (PF + LN) usually in combination with androgen deprivation (AD) therapy. Any failure not detected on conventional imaging was delineated with PSMA-PET scanning. Sites of failure were characterised as in-field (PF ± LN), or out of field (nodal alone, distant metastatic alone (visceral or bone) or multi-site failure). Nodal failure was further divided into pelvic failure and/or distant failure. 119 men developed BF, defined as a PSA rise of >0.2 or greater, above post-RT nadir. Freedom from BF was 71% in the PF group and 70% in the PF + LN group, with median follow up of 52 and 44 months respectively. AD was used concomitantly in 13% of the PF group and 92% of the PF + LN group. 81 patients with BF (68%) had PSMA-PET imaging performed as per study intent, 67 (80%) of whom had PSMA avid disease identified. PSMA-PET delineated in-field failure occurred in 2/50 (4%) of the PF group and 1/17 (6%) in the PF + LN group. Nodal failure alone was 33/50 (66%) for the PF group vs 7/17 (41%) for the PF + LN group. For the nodal only failure patients, 18/33 (55%) had pelvic-only nodal failure in the PF group compared to 1/7 (14%) in the PF + LN group (p = 0.03). 16 (32%) of the PSMA avid failures in the PF group would have been encompassed by standard pelvic lymphatic radiotherapy volumes. Post-prostatectomy radiation treatment resulted in excellent in-field control rates. Isolated pelvic nodal failure was rare in those receiving radiotherapy to the prostatic fossa and pelvic nodes but accounted for one third of

  14. Clinical Investigation of Treatment Failure in Type 2 Diabetic ...

    African Journals Online (AJOL)

    HP

    contributory factors in treatment failure in type 2 diabetic patients taking metformin and glibenclamide in a tertiary ... that took metformin and glibenclamide for a minimum of 1 year were examined. Patients ..... obesity in adults and children.

  15. Erythropoietin treatment does not compromise cardiovascular function in chronic renal failure

    DEFF Research Database (Denmark)

    Haedersdal, C; Mehlsen, J; Stenver, Doris Irene

    1994-01-01

    The anemia in patients with chronic renal failure can be corrected through treatment with recombinant human erythropoietin treatment. This correction is associated with changes in the rheologic variables, which could explain the changes in hemodynamics found by many investigators. The authors have...... followed up 11 patients with chronic renal failure on hemodialysis before and during six months of therapy with erythropoietin. The measurements were made before treatment, after four months of therapy, and after six months of therapy. The measurements included hematocrit, osmotic resistance of the red...... were unchanged. The conclude that, in spite of changes in rheologic variables, increasing viscosity of the blood and thus possibly increasing the peripheral resistance, these had no effect on the cardiovascular state. Erythropoietin treatment improves the subjective well-being in patients on chronic...

  16. Factors associated with failure of nonoperative treatment in lateral epicondylitis.

    Science.gov (United States)

    Knutsen, Elisa J; Calfee, Ryan P; Chen, Raymond E; Goldfarb, Charles A; Park, Kevin W; Osei, Daniel A

    2015-09-01

    Lateral epicondylitis is a common cause of elbow pain that is treated with a variety of nonoperative measures and often improves with time. Minimal research is available on patients in whom these nonoperative treatments fail. To identify baseline patient and disease factors associated with the failure of nonoperative treatment of lateral epicondylitis, defined as surgery after a period of nonoperative treatment. Case control study; Level of evidence, 3. A total of 580 patients treated for lateral epicondylitis at a tertiary center between 2007 and 2012 were analyzed. Disease-specific and patient demographic characteristics were compared between patient groups (nonoperative vs surgical treatment). A multivariable logistic regression model was created based on preliminary univariate testing to determine which characteristics were associated with failure of nonoperative treatment. Of the 580 patients, 92 (16%) underwent surgical treatment at a mean of 6 months (range, 0-31 months) from their initial visit. Univariate analysis demonstrated a potential association (P 12 months (OR, 2.5) remained significant independent predictors of surgical treatment. This study identifies risk factors for surgical treatment for lateral epicondylitis. While these findings do not provide information regarding causal factors associated with surgery, these patient and disease-specific considerations may be helpful when counseling patients regarding treatment options and the likelihood of the success of continued nonoperative treatment. © 2015 The Author(s).

  17. Successful Treatment of Fibrosing Organising Pneumonia Causing Respiratory Failure with Mycophenolic Acid.

    Science.gov (United States)

    Paul, Christina; Lin-Shaw, Ammy; Joseph, Mariamma; Kwan, Keith; Sergiacomi, Gianluigi; Mura, Marco

    2016-01-01

    Organising pneumonia (OP) is usually promptly responsive to corticosteroid treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven fibrosing OP causing respiratory failure. All cases presented with peribronchial and subpleural consolidations, had a fibro-inflammatory infiltrative component in the alveolar septa, and only had a partial and unsatisfactory response to corticosteroids. However, they responded to mycophenolic acid (MPA) treatment with resolution of respiratory failure as well as clinical and functional improvement. MPA as an additional treatment option for aggressive forms of fibrosing OP and interstitial lung disease needs to be further explored. © 2016 S. Karger AG, Basel.

  18. Chronic antidiabetic sulfonylureas in vivo: reversible effects on mouse pancreatic beta-cells.

    Directory of Open Access Journals (Sweden)

    Maria Sara Remedi

    2008-10-01

    Full Text Available Pancreatic beta-cell ATP-sensitive potassium (K ATP channels are critical links between nutrient metabolism and insulin secretion. In humans, reduced or absent beta-cell K ATP channel activity resulting from loss-of-function K ATP mutations induces insulin hypersecretion. Mice with reduced K ATP channel activity also demonstrate hyperinsulinism, but mice with complete loss of K ATP channels (K ATP knockout mice show an unexpected insulin undersecretory phenotype. Therefore we have proposed an "inverse U" hypothesis to explain the response to enhanced excitability, in which excessive hyperexcitability drives beta-cells to insulin secretory failure without cell death. Many patients with type 2 diabetes treated with antidiabetic sulfonylureas (which inhibit K ATP activity and thereby enhance insulin secretion show long-term insulin secretory failure, which we further suggest might reflect a similar progression.To test the above hypotheses, and to mechanistically investigate the consequences of prolonged hyperexcitability in vivo, we used a novel approach of implanting mice with slow-release sulfonylurea (glibenclamide pellets, to chronically inhibit beta-cell K ATP channels. Glibenclamide-implanted wild-type mice became progressively and consistently diabetic, with significantly (p < 0.05 reduced insulin secretion in response to glucose. After 1 wk of treatment, these mice were as glucose intolerant as adult K ATP knockout mice, and reduction of secretory capacity in freshly isolated islets from implanted animals was as significant (p < 0.05 as those from K ATP knockout animals. However, secretory capacity was fully restored in islets from sulfonylurea-treated mice within hours of drug washout and in vivo within 1 mo after glibenclamide treatment was terminated. Pancreatic immunostaining showed normal islet size and alpha-/beta-cell distribution within the islet, and TUNEL staining showed no evidence of apoptosis.These results demonstrate that

  19. Failure pattern and salvage treatment after radical treatment of head and neck cancer

    DEFF Research Database (Denmark)

    Pagh, Anja; Grau, Cai; Overgaard, Jens

    2016-01-01

    Purpose The aim of the study was to test the hypothesis that head and neck cancer (HNC) patients benefit from specialized follow-up (FU), as this strategy ensures timely detection of relapses for successful salvage treatment. This was done by evaluation of the pattern of failure, the temporal...... recordings of recurrent disease in 567 patients with primary tumors of the larynx, pharynx, oral cavity, nasal cavity, paranasal sinuses and salivary glands. A review of medical records was performed in order to update and supplement the database. Results Failures of the 567 patients were primarily in T...

  20. Treatment of the complex abdomen and acute intestinal failure

    NARCIS (Netherlands)

    de Vries, F.E.E.

    2018-01-01

    Management of the complex abdomen and acute intestinal failure (IF) is challenging and requires specialized multidisciplinary treatment. Due to the small numbers and heterogeneity of the patient group high-quality evidence for some of the research questions is probably unachievable. Nevertheless,

  1. Assessment of obstructive sleep apnoea treatment success or failure after maxillomandibular advancement.

    Science.gov (United States)

    de Ruiter, M H T; Apperloo, R C; Milstein, D M J; de Lange, J

    2017-11-01

    Maxillomandibular advancement (MMA) is an alternative therapeutic option that is highly effective for treating obstructive sleep apnoea (OSA). MMA provides a solution for OSA patients that have difficulty accepting lifelong treatments with continuous positive airway pressure or mandibular advancement devices. The goal of this study was to investigate the different characteristics that determine OSA treatment success/failure after MMA. The apnoea-hypopnoea index (AHI) was used to determine the success or failure of OSA treatment after MMA. Sixty-two patients underwent MMA for moderate and severe OSA. A 71% success rate was observed with a mean AHI reduction of 69%. A statistically significant larger neck circumference was measured in patients with failed OSA treatments following MMA (P=0.008), and older patients had failed OSA treatments with MMA: 58 vs. 53 years respectively (P=0.037). Cephalometric analysis revealed no differences between successful and failed OSA treatment outcomes. There was no difference in maxillary and mandibular advancements between success and failed MMA-treated OSA patients. The complications most frequently reported following MMA were sensory disturbances in the inferior alveolar nerve (60%) and malocclusion (24%). The results suggest that age and neck girth may be important factors that could predict susceptibility to OSA treatment failures by MMA. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. Antibiotic treatment failure when consulting patients with respiratory tract infections in general practice

    DEFF Research Database (Denmark)

    Bordado Sköld, Margrethe; Aabenhus, Rune; Guassora, Ann Dorrit

    2017-01-01

    as cases of antibiotic treatment failure (ATF). Objectives: We studied antibiotic treatment failure in patients with acute RTIs from a general practitioner (GP) perspective, aiming to explore (i) GPs’ views of ATF in primary care; (ii) how ATF influences the doctor-patient relationship; and (iii) GPs....... GPs used many communicative tools to maintain trust with patients in cases of ATF, but they did not consider such incidents to affect the doctor-patient relationship adversely. Conclusion: These findings suggest a possible communication gap between doctors and patients, partly due to a narrow medical...... definition of ATF. Studies describing patients’ views are still missing. General practitioners’ experiences and views on antibiotic treatment failure in acute respiratory infections or its effects on the doctor–patient relationship have not been studied previously....

  3. A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

    Science.gov (United States)

    Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

    2018-03-20

    Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

  4. [Treatment Strategy and Results of Carotid Endarterectomy in Chronic Renal Failure Patients].

    Science.gov (United States)

    Murahashi, Takeo; Kamiyama, Kenji; Osato, Toshiaki; Watanabe, Toshiichi; Ogino, Tatsuya; Sugio, Hironori; Endo, Hideki; Takahira, Kazuki; Shindo, Koichiro; Takahashi, Shuhei; Nakamura, Hirohiko

    2017-02-01

    The number of patients receiving chronic dialysis treatment in Japan currently exceeds 300,000 people. Few reports have described carotid endarterectomy(CEA)for chronic renal failure patients because of the unacceptable rate of perioperative stroke and other morbidities. A strategy for and treatment results of CEA for chronic renal failure patients in our hospital are described herein. The present study included 6 patients who underwent CEA while receiving dialysis treatment between April 2011 and November 2014. Dialysis treatment was initiated due to diabetes in 4 patients and renal sclerosis in 2 patients. All the patients were men, with a mean age of 74.0 years. Two patients were symptomatic, and four were asymptomatic. In all the patients, heart vascular lesions and arteriosclerosis risk factors were present. Postoperatively, pneumonia transient cranial neuropathy, heart failure, and pneumonia in 1 case required extensive treatment. However, by the time of discharge from hospital, no cases had deteriorated compared with their pre-CEA state. The modified Rankin scale score on discharge was 0-2 for all the patients. CEA can be performed safely in patients receiving dialysis, but further operative procedures and careful postoperative management are likely to be needed for patients with CEA who are receiving dialysis.

  5. Chiari malformations: diagnosis, treatments and failures.

    Science.gov (United States)

    Abd-El-Barr, M M; Strong, C I; Groff, M W

    2014-12-01

    Chiari malformations refer to abnormalities of the hindbrain originally described by the Austrian pathologist Hans Chiari in the early 1890s. These malformations range from herniation of the cerebellar tonsils through the foramen magnum to complete agenesis of the cerebellum. In this review, we review the different classification schemes of Chiari malformations. We discuss the different signs and symptoms that the two most common malformations present with and diagnostic criteria. We next discuss current treatment paradigms, including the new measure of possible in utero surgery to help decrease the incidence of Chiari type II malformations. There is also a small discussion of treatment failures and salvage procedures in these difficult cases. Chiari malformations are a difficult clinical entity to treat. As more is learned about the genetic and environmental factors relating to their characteristics, it will be interesting if we are able to predict which treatments are better suited for different patients. Similarly, with the evolution of in utero techniques especially for Chiari II malformations, it will be interesting to see if the incidence and practice of treating these difficult patients will change.

  6. Rilpivirine versus etravirine validity in NNRTI-based treatment failure in Thailand.

    Science.gov (United States)

    Teeranaipong, Phairote; Sirivichayakul, Sunee; Mekprasan, Suwanna; Ruxrungtham, Kiat; Putcharoen, Opass

    2014-01-01

    Etravirine (ETR) and rilpivirine (RPV) are the second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI) for treatment of HIV-1 infection. Etravirine is recommended for patients with virologic failure from first generation NNRTI-based regimen [1]. RPV has profile with similar properties to ETR but this agent is approved for treatment-naïve patients [2]. In Thailand, ETR is approximately 45 times more expensive than RPV. We aimed to study the patterns of genotypic resistance and possibility of using RPV in patients with virologic failure from two common NNRTI-based regimens: efavirenz (EFV)- or nevirapine (NVP)-based regimen. Data of clinical samples with confirmed virologic failure during 2003-2010 were reviewed. We selected the samples from patients who failed EFV- or NVP-based regimen. Resistance-associated mutations (RAMs) were determined by IAS-USA Drug Resistance Mutations. DUET, Monogram scoring system and Stanford Genotypic Resistance Interpretation were applied to determine the susceptibility of ETR and RPV. A total of 2086 samples were analyzed. Samples from 1482 patients with virologic failure from NVP-based regimen treatment failure (NVP group) and 604 patients with virologic failure from EFV-based regimen treatment failure (EFV group) were included. 95% of samples were HIV-1 CRF01_AE subtype. Approximately 80% of samples in each group had one to three NNRTI-RAMs and 20% had four to seven NNRTI-RAMs. 181C mutation was the most common NVP-associated RAM (54.3% vs 14.7%, p<0.01). 103N mutation was the most common EFV-associated RAM (56.5% vs 19.1%, p<0.01). The calculated scores from all three scoring systems were concordant. In NVP group, 165 (11.1%) and 161 (10.9%) patients were susceptible to ETR and RPV, respectively (p=0.81). In EFV group, 195 (32.2%) and 191 (31.6%) patients were susceptible to ETR and RPV, respectively (p=0.81). The proportions of viruses that remained susceptible to ETR and RPV in EFV group were significantly

  7. ACE inhibitors and calcium antagonists in the treatment of congestive heart failure

    DEFF Research Database (Denmark)

    Hansen, J F

    1995-01-01

    heart failure in the SOLVD trials. In post-myocardial infarction patients, the calcium antagonist nifedipine did not affect mortality or morbidity; diltiazem improved prognosis in patients without congestive heart failure and in patients with non-Q-wave infarction; and verapamil improved prognosis...... by prevention of reinfarction and sudden death. Combination treatment with both verapamil, which has pronounced antiischemic properties and prevents sudden death and reinfarction, and an ACE inhibitor, which prevents the progression of heart failure, is a possibility for future cardiovascular therapy...

  8. Successful adalimumab treatment of a psoriasis vulgaris patient with hemodialysis for renal failure: A case report and a review of the previous reports on biologic treatments for psoriasis patients with hemodialysis for renal failure.

    Science.gov (United States)

    Kusakari, Yoshiyuki; Yamasaki, Kenshi; Takahashi, Toshiya; Tsuchiyama, Kenichiro; Shimada-Omori, Ryoko; Nasu-Tamabuchi, Mei; Aiba, Setsuya

    2015-07-01

    The efficacy and safety of biologic treatments have been established in patients with moderate to severe psoriasis, but there are few reports on biologic therapy for patients with psoriasis complicated by end-stage renal failure on hemodialysis (HD). In this report, we demonstrated the efficacy and safety of adalimumab for patients with severe psoriasis on HD. A 46-year-old Japanese man with a 14-year history of psoriasis was referred to our clinic in September 2009. He had developed hypertension and renal failure during a 7-year history of cyclosporin treatment. With the infliximab treatment, he achieved 75% improvement of the Psoriasis Area and Severity Index (PASI) score within 3 months from the PASI of 42.3 before the treatment. However, his renal failure gradually deteriorated, and HD was initiated at 1 year after the introduction of infliximab. Because of hydration during the i.v. injection of infliximab, he developed pulmonary edema with every infliximab treatment after starting HD. We switched to ustekinumab treatment, but his psoriasis was not improved. Then, we switched to adalimumab and achieved a PASI-100 response within 2 months. The patient received adalimumab treatment for more than a year without any adverse effects. In addition to our case, five articles reported cases of psoriasis patients with renal failure on HD who were treated with biologics. The psoriatic lesions were improved by biologics in these cases, and no severe adverse effects on the renal function were reported. Thus, biologics are a reasonable treatment option for patients with severe psoriasis with renal failure on HD. © 2015 Japanese Dermatological Association.

  9. What causes treatment failure - the patient, primary care, secondary care or inadequate interaction in the health services?

    Directory of Open Access Journals (Sweden)

    Lange Ove

    2011-05-01

    Full Text Available Abstract Background Optimal treatment gives complete relief of symptoms of many disorders. But even if such treatment is available, some patients have persisting complaints. One disorder, from which the patients should achieve complete relief of symptoms with medical or surgical treatment, is gastroesophageal reflux disease (GERD. Despite the fact that such treatment is cheap, safe and easily available; some patients have persistent complaints after contact with the health services. This study evaluates the causes of treatment failure. Methods Twelve patients with GERD and persistent complaints had a semi-structured interview which focused on the patients' evaluation of treatment failure. The interviews were taped, transcribed and evaluated by 18 physicians, (six general practitioners, six gastroenterologists and six gastrointestinal surgeons who completed a questionnaire for each patient. The questionnaires were scored, and the relative responsibility for the failure was attributed to the patient, primary care, secondary care and interaction in the health services. Results Failing interaction in the health services was the most important cause of treatment failure, followed by failure in primary care, secondary care and the patient himself; the relative responsibilities were 35%, 28%, 27% and 10% respectively. There was satisfactory agreement about the causes between doctors with different specialities, but significant inter-individual differences between the doctors. The causes of the failures differed between the patients. Conclusions Treatment failure is a complex problem. Inadequate interaction in the health services seems to be important. Improved communication between parts of the health services and with the patients are areas of improvement.

  10. Analysis of Initial Baseline Clinical Parameters and Treatment Strategy Associated with Medication Failure in the Treatment of Benign Prostatic Hyperplasia in Korea

    Directory of Open Access Journals (Sweden)

    Hoon Choi

    2010-12-01

    Full Text Available Purpose To analyze the baseline clinical factors and medication treatment strategy used in cases with medication treatment failure of benign prostatic hyperplasia (BPH. Methods From January 2006 to December 2009, 677 BPH patients with at least 3 months of treatment with medication were enrolled. We analyzed clinical factors by medication failure (n=161 versus maintenance (n=516, by prostate size (less than 30 g, n=231; 30 to 50 g, n=244; greater than 50 g, n=202, and by prostate-specific antigen (PSA levels (less than 1.4 ng/mL, n=324; more than 1.4 ng/mL, n=353. Results Age, combination medication rate, PSA, and prostate volume were statistically different between the medication treatment failure and maintenance groups. By prostate size, the PSA and medication failure rates were relatively higher and the medication period was shorter in patients with a prostate size of more than 30 g. The combination medication rate was higher in patients with a prostate size of more than 50 g. The medication failure rate and prostate volume were higher in patients with a PSA level of more than 1.4 ng/mL. However, the combination treatment rate was not significantly different in patients with a PSA level lower than 1.4 ng/mL. Suggestive cutoffs for combination medication are a prostate volume of 34 g and PSA level of 1.9 ng/mL. Conclusions The clinical factors associated with medication failure were age, treatment type, and prostate volume. Combination therapy should be considered more in Korea in patients with a PSA level higher than 1.4 ng/mL and a prostate volume of between 30 and 50 g to prevent medication failure.

  11. In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Cristina Botella

    Full Text Available Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31 versus an Augmented Reality system (N = 32 in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

  12. In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial.

    Science.gov (United States)

    Botella, Cristina; Pérez-Ara, M Ángeles; Bretón-López, Juana; Quero, Soledad; García-Palacios, Azucena; Baños, Rosa María

    2016-01-01

    Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31) versus an Augmented Reality system (N = 32) in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants.

  13. Risk factors for tuberculosis treatment failure, default, or relapse and outcomes of retreatment in Morocco.

    Science.gov (United States)

    Dooley, Kelly E; Lahlou, Ouafae; Ghali, Iraqi; Knudsen, Janine; Elmessaoudi, My Driss; Cherkaoui, Imad; El Aouad, Rajae

    2011-02-28

    Patients with tuberculosis require retreatment if they fail or default from initial treatment or if they relapse following initial treatment success. Outcomes among patients receiving a standard World Health Organization Category II retreatment regimen are suboptimal, resulting in increased risk of morbidity, drug resistance, and transmission.. In this study, we evaluated the risk factors for initial treatment failure, default, or early relapse leading to the need for tuberculosis retreatment in Morocco. We also assessed retreatment outcomes and drug susceptibility testing use for retreatment patients in urban centers in Morocco, where tuberculosis incidence is stubbornly high. Patients with smear- or culture-positive pulmonary tuberculosis presenting for retreatment were identified using clinic registries in nine urban public clinics in Morocco. Demographic and outcomes data were collected from clinical charts and reference laboratories. To identify factors that had put these individuals at risk for failure, default, or early relapse in the first place, initial treatment records were also abstracted (if retreatment began within two years of initial treatment), and patient characteristics were compared with controls who successfully completed initial treatment without early relapse. 291 patients presenting for retreatment were included; 93% received a standard Category II regimen. Retreatment was successful in 74% of relapse patients, 48% of failure patients, and 41% of default patients. 25% of retreatment patients defaulted, higher than previous estimates. Retreatment failure was most common among patients who had failed initial treatment (24%), and default from retreatment was most frequent among patients with initial treatment default (57%). Drug susceptibility testing was performed in only 10% of retreatment patients. Independent risk factors for failure, default, or early relapse after initial treatment included male gender (aOR = 2.29, 95% CI 1

  14. Liver failure posthepatectomy and biliary fistula: multidisciplinar treatment.

    Science.gov (United States)

    Calleja Kempin, Javier; Colón Rodríguez, Arturo; Machado Liendo, Pedro; Acevedo, Agustín; Martín Gil, Jorge; Sánchez Rodríguez, Teresa; Zorrilla Matilla, Laura

    2016-05-01

    The main cause of morbimor-mortality after major liver surgery is the development of liver failure posthepatectomy(LFPH). Treatment must involve multiple options and will be aggressive from the beginning. We report a case of a patient with cholangiocarcinoma perihilar treated with surgery: right hepatectomy extended to sI + IVb with develop of LFPH and biliary fistula and being management successfully in a multidisciplinary way.

  15. Predictors of treatment failure, incipient hypothyroidism, and weight gain following radioiodine therapy for Graves' thyrotoxicosis.

    Science.gov (United States)

    Gibb, F W; Zammitt, N N; Beckett, G J; Strachan, M W J

    2013-10-01

    Following radioiodine ((131)I) therapy, both late recognition of hypothyroidism and treatment failure may result in adverse outcomes. We sought to assess indicators of both incipient hypothyroidism and treatment failure following (131)I and determine factors predictive of weight gain. Retrospective study of 288 patients receiving (131)I for treatment of Graves' thyrotoxicosis. Primary outcome measures were thyroid status and weight change at 1 yr following (131)I. The treatment failure rate at 1 yr was 13.5%. Hypothyroidism developed in 80.9%, with 58.5% of patients having levels of free T4 (fT4) treatment failure (23.3%) than those with no thionamide exposure (6.3%, p=0.003), but also had more active Graves' disease. Following (131)I, development of a detectable TSH or low-normal fT4 levels was not associated with recurrent thyrotoxicosis. Median weight gain was 5.3 kg, although patients with nadir fT4 levels 6 pmol/l (p=0.05). The main predictor of weight gain was fT4 level immediately prior to treatment; those in the lowest tertile gained a median 3.1 kg whilst those in the highest tertile gained 7.4 kg (median difference 4.3 kg; 95% confidence interval: 2.5-6.2). Marked hypothyroidism following (131)I is common and often occurs early. Simple biochemical parameters may help identify incipient hypothyroidism and potentially limit excess weight gain. Treatment failure is common in patients with severe thyrotoxicosis and in such cases larger doses of (131)I may be warranted.

  16. The role of exogenous risk factors of antituberculosis treatment failure

    OpenAIRE

    LESNIC, EVELINA; USTIAN, AURELIA; POP, CARMEN MONICA

    2016-01-01

    Background and aim The Republic of Moldova reports the highest incidence of tuberculosis and the lowest treatment success rate among European region countries. In most of the patients the antituberculosis treatment failure is correlated with social risk factors (low socio-economical state, epidemiological danger characteristics) and biological factors (young age, male sex, physiological conditions, associated diseases). Clinical factors (advanced forms of tuberculosis, chronic evolution, immu...

  17. Quality assurance of the treatments performed with a linear accelerator by means of in vivo dosimetry

    International Nuclear Information System (INIS)

    Jornet, N.; Ribas, M.; Eudaldo, T.; Carrasco, P.

    2001-01-01

    In vivo dosimetry by means of diode detectors has been used routinely in our hospital since 1996 to guarantee the dose administrated to patients undergoing a radiotherapy treatment. The aim of this work is to present how in vivo dosimetry was implemented in our centre and which kind of errors have been discovered and corrected. Before the implementation it has to be clear which kind of errors want to be traced, the tolerance and action level, who will perform the measurements and who will evaluate them. Once all these things are clear, the first thing to do is to choose the more appropriate type of diodes and to calibrate them. The lower the tolerance level, the more accurate the calibration has to be. At this point the training and motivation of people who will be involved is very important to succeed in implementing routine use of in vivo dosimetry. Choosing one treatment unit and one easy and frequent treatment technique is a good way of starting implementation. We started with prostate treatments. In vivo entrance and exit doses were measured and dose to the ICRU point was calculated. Nowadays in vivo dosimetry is performed in the second session of all treatments (X-rays and electrons). (author)

  18. Treatment verification and in vivo dosimetry for total body irradiation using thermoluminescent and semiconductor detectors

    International Nuclear Information System (INIS)

    Oliveira, F.F.; Amaral, L.L.; Costa, A.M.; Netto, T.G.

    2014-01-01

    The objective of this work is the characterization of thermoluminescent and semiconductor detectors and their applications in treatment verification and in vivo dosimetry for total body irradiation (TBI) technique. Dose measurements of TBI treatment simulation performed with thermoluminescent detectors inserted in the holes of a “Rando anthropomorphic phantom” showed agreement with the prescribed dose. For regions of the upper and lower chest where thermoluminescent detectors received higher doses it was recommended the use of compensating dose in clinic. The results of in vivo entrance dose measurements for three patients are presented. The maximum percentual deviation between the measurements and the prescribed dose was 3.6%, which is consistent with the action level recommended by the International Commission on Radiation Units and Measurements (ICRU), i.e., ±5%. The present work to test the applicability of a thermoluminescent dosimetric system and of a semiconductor dosimetric system for performing treatment verification and in vivo dose measurements in TBI techniques demonstrated the value of these methods and the applicability as a part of a quality assurance program in TBI treatments. - Highlights: • Characterization of a semiconductor dosimetric system. • Characterization of a thermoluminescent dosimetric system. • Application of the TLDs for treatment verification in total body irradiation treatments. • Application of semiconductor detectors for in vivo dosimetry in total body irradiation treatments. • Implementation of in vivo dosimetry as a part of a quality assurance program in radiotherapy

  19. Ex vivo repair of renal artery aneurysm associated with surgical treatment of abdominal aortic aneurysm

    Directory of Open Access Journals (Sweden)

    Kostić Dušan M.

    2004-01-01

    shorter arteries was implanted into the long artery, and another one into PTFE graft. After 30 minutes of explanation, autotransplantation of the kidney into the right iliac fossa was performed. The right renal vein was implanted into the inferior vein cava, and PTFE graft into the right limb of Dacron graft. Immediately following the completion of both anastomoses, large volume of urine was evident. Finally, ureteneocystostomy was performed with previous insertion of double "J" catheter. In the immediate postoperative period, renal function was restored to normal, while postoperative angiography revealed all patent grafts. DISCUSSION The most common causes of renal artery aneurysms are arteriosclerosis, as in our case, and fibro-muscular dysplasia. Very often, renal artery aneurysms are asymptomatic and discovered only during angiography in patients with aneurysmal and occlusive aortic disease. Other cases include: arterial hypertension, groin pain and acute or chronic renal failure. Due to relatively small number of evaluated cases, the risk of aneurysmal rupture is not known. According to some authors, the overall rupture rate of renal artery aneurysm is 5%, however, the rupture risk becomes higher in young pregnant woman. Several standard surgical procedures are available for the repair of renal artery aneurysms. These include saphenous vein angioplasty, bypass grafting, as well as ex vivo reconstruction with reimplantation or autotransplantation. Furthermore, interventional embolization therapy, as well as endovascular treatment with ePTFE covered stent, or autologous vein-coverage stent graft, have been also reported to be successful. CONCLUSION The major indications for surgical treatment of renal artery aneurysms are to eliminate the source of thromboembolism which leads to fixed renal hypertension and kidney failure, as well as prevention of aneurysmal rupture.

  20. Adherence to the European Society of Cardiology guidelines for the treatment of chronic heart failure

    Science.gov (United States)

    Sitepu, A.; Hamdani, K.

    2018-03-01

    Heart failure is a tremendous health problem with significant morbidity and mortality. The treatment of heart failure should be applied appropriately to improve the successful management of patients. This study aims to evaluate the adherence to European Society of Cardiology (ESC) guidelines for the treatment of chronic heart failure and to determine factors associated with guideline adherence. This study is an observational study comprising 97 patients with chronic heart failure with reduced ejection fraction. The guideline adherence was assessed the by the use of guideline adherence indicator (GAI), which consider GAI-3 or GAI-5, by calculating the proportion of recommended drugs was prescribed divided by a number of drugs indicated according to the ESC guidelines, in the absence of contraindications. The results showed the use of each indicated drugs were angiotensin- converting enzyme inhibitors or angiotensin receptor blockers (78.4%), beta-blockers (61.9%), mineralocorticoid receptor antagonists (61.9%), diuretics (89.7%), and digitalis (26.8%). Furthermore, the predominant categories of GAI-3 and GAI-5 were moderate. This study demonstrates that the adherence to ESC guidelines for the treatment of chronic heart failure still needs to be improved compared to recent studies. Also, age, etiology of heart failure and comorbidity were associated factors that influence the implementation of ESC guidelines.

  1. Risk Factors of Treatment Failure in Diabetic Foot Ulcer Patients

    Directory of Open Access Journals (Sweden)

    Kyung Mook Lee

    2013-03-01

    Full Text Available BackgroundSome diabetic feet heal without complication, but others undergo amputation due to progressive wounds. This study investigates the risk factors for amputation of diabetic feet.MethodsA total of 55 patients who visited our institution from 2008 to 2012 were included in the study. The patients with abnormal fasting blood sugar levels, lower leg vascularity, and poor nutrition were excluded from the study group, and the wound states were unified. The patients were categorized into a treatment success group (n=47 and a treatment failure group (n=8, and their hemoglobin A1C (HgA1C, C-reactive protein (CRP, white blood cell count (WBC, and serum creatinine levels were analyzed.ResultsThe initial CRP, WBC, and serum creatinine levels in the treatment failure group were significantly higher than that of the treatment success group, and the initial HgA1C level was significantly higher in the treatment success group. The CRP and WBC levels of both groups changed significantly as time passed, but their serum creatinine levels did not.ConclusionsThe initial CRP, WBC, and serum creatinine levels were considered to be risk factors for amputation. Among them, the serum creatinine level was found to be the most important predictive risk factor. Because serum creatinine represents the renal function, thorough care is needed for the feet of diabetic patients with renal impairment.

  2. TREATMENT OF CHRONIC HEART FAILURE: FOCUS ON METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2012-01-01

    Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.

  3. TREATMENT OF CHRONIC HEART FAILURE: FOCUS ON METOPROLOL SUCCINATE

    Directory of Open Access Journals (Sweden)

    O. D. Ostroumova

    2015-12-01

    Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.

  4. First-drug treatment failures in 42 Turkish children with idiopathic childhood occipital epilepsies.

    Science.gov (United States)

    Incecik, Faruk; Herguner, Ozlem M; Altunbasak, Sakir

    2015-01-01

    The early and late benign occipital epilepsies of childhood (BOEC) are described as two discrete electro-clinical syndromes, eponymously known as Panayiotopoulos and Gastaut syndromes. The purpose of this study was to identify predictors of failure to respond to the initial antiepileptic drug (AED). A total of 42 children with BOEC were enrolled. Predictive factors were analyzed by survival methods. Among the 42, 25 patients (59.5%) were boys and 17 (40.5%) were girls and the mean age at the seizure onset was 7.46 ± 2.65 years (4-14 years). Of the 42 patients, 34 (81.0%) were treated relatively successfully with the first AED treatment, and 8 (19.0%) were not responded initial AED treatment. There was no correlation between response to initial AED treatment and sex, consanguinity, epilepsy history of family, age of seizure onset, frequency of seizures, history of status epilepticus, duration of starting first treatment, findings on electroencephalogram. However, history of febrile seizure and type of BOEC were significantly associated with failure risk. Factors predicting failure to respond to the AED were history of febrile seizure and type of BOEC in children with BOEC.

  5. Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure

    DEFF Research Database (Denmark)

    Feldman, Ted; Komtebedde, Jan; Burkhoff, Daniel

    2016-01-01

    UNLABELLED: Heart failure with preserved ejection fraction (HFpEF), a major public health problem with high morbidity and mortality rates, remains difficult to manage because of a lack of effective treatment options. Although HFpEF is a heterogeneous clinical syndrome, elevated left atrial pressu...

  6. Mycoplasma genitalium infection: current treatment options, therapeutic failure, and resistance-associated mutations

    Directory of Open Access Journals (Sweden)

    Couldwell DL

    2015-05-01

    Full Text Available Deborah L Couldwell,1,2 David A Lewis1,21Western Sydney Sexual Health Centre, Parramatta, 2Centre for Infectious Diseases and Microbiology and Marie Bashir Institute for Infectious Diseases and Biosecurity, Westmead Clinical School, University of Sydney, Sydney, NSW, Australia Abstract: Mycoplasma genitalium is an important cause of non-gonococcal urethritis, cervicitis, and related upper genital tract infections. The efficacy of doxycycline, used extensively to treat non-gonococcal urethritis in the past, is relatively poor for M. genitalium infection; azithromycin has been the preferred treatment for several years. Research on the efficacy of azithromycin has primarily focused on the 1 g single-dose regimen, but some studies have also evaluated higher doses and longer courses, particularly the extended 1.5 g regimen. This extended regimen is thought to be more efficacious than the 1 g single-dose regimen, although the regimens have not been directly compared in clinical trials. Azithromycin treatment failure was first reported in Australia and has subsequently been documented in several continents. Recent reports indicate an upward trend in the prevalence of macrolide-resistant M. genitalium infections (transmitted resistance, and cases of induced resistance following azithromycin therapy have also been documented. Emergence of antimicrobial-resistant M. genitalium, driven by suboptimal macrolide dosage, now threatens the continued provision of effective and convenient treatments. Advances in techniques to detect resistance mutations in DNA extracts have facilitated correlation of clinical outcomes with genotypic resistance. A strong and consistent association exists between presence of 23S rRNA gene mutations and azithromycin treatment failure. Fluoroquinolones such as moxifloxacin, gatifloxacin, and sitafloxacin remain highly active against most macrolide-resistant M. genitalium. However, the first clinical cases of moxifloxacin treatment

  7. Experimental Simulation of the Effects of an Initial Antibiotic Treatment on a Subsequent Treatment after Initial Therapy Failure

    NARCIS (Netherlands)

    Feng, Yanfang; Händel, Nadine; de Groot, Marnix H. P.; Brul, Stanley; Schultsz, Constance; ter Kuile, Benno H.

    2014-01-01

    Therapy failure of empirical antibiotic treatments prescribed by primary care physicians occurs commonly. The effect of such a treatment on the susceptibility to second line antimicrobial drugs is unknown. Resistance to amoxicillin was rapidly induced or selected in E. coli at concentrations

  8. Neprilysin inhibition with sacubitril/valsartan in the treatment of heart failure: mortality bang for your buck.

    Science.gov (United States)

    Ansara, A J; Kolanczyk, D M; Koehler, J M

    2016-04-01

    Heart failure remains a leading cause of morbidity and mortality worldwide. Advanced therapies have prolonged survival in patients with advanced heart failure, but pharmacotherapeutic optimization remains the mainstay of treatment. It has been over 10 years since the last mortality-reducing medication has been approved by the Food and Drug Administration. This article reviews the background, current knowledge and data supporting the use of sacubitril/valsartan (Entresto(®) ), the newly FDA-approved medication that dually inhibits angiotensin and neprilysin, in the treatment of heart failure. A literature search was performed (January 1980 to August 2015) using PubMed and the search terms were as follows: neprilysin inhibitor, heart failure, endopeptidase, natriuretic peptides, angiotensin, omapatrilat, LCZ696, valsartan and sacubitril. Peer-reviewed, published clinical trials, review articles, relevant treatment guidelines and prescribing information documents were identified and reviewed for relevance. Additionally, reference citations from publications identified were reviewed. The inhibition of endopeptidases has been an area of extensive study for the treatment of heart failure. Previously published literature with the endopeptidase inhibitor omapatrilat failed to demonstrate a sufficient balance between clinical efficacy and safety to justify its approval. Omapatrilat blocked three pathways that break down bradykinin, leading to high rates of angioedema. Sacubitril, on the other hand, is metabolized to a form that is highly selective for neprilysin without possessing activity for the other two peptidases, ACE and APP. The combination of sacubitril with valsartan in a single formulation offers the benefit of concurrent blockade of the renin angiotensin aldosterone system and the inhibition of neprilysin while minimizing angioedema risk. When compared to ACE inhibitor therapy in systolic heart failure patients, sacubitril/valsartan demonstrated reductions in

  9. Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Qayyum, Abbas Ali; Jørgensen, Erik

    2015-01-01

    AIMS: Regenerative treatment with mesenchymal stromal cells (MSCs) has been promising in patients with ischaemic heart failure but needs confirmation in larger randomized trials. We aimed to study effects of intra-myocardial autologous bone marrow-derived MSC treatment in patients with severe isc...... identified. CONCLUSION: Intra-myocardial injections of autologous culture expanded MSCs were safe and improved myocardial function in patients with severe ischaemic heart failure. STUDY REGISTRATION NUMBER: NCT00644410 (ClinicalTrials.gov)....... ischaemic heart failure. METHODS AND RESULTS: The MSC-HF trial is a randomized, double-blind, placebo-controlled trial. Patients were randomized 2 : 1 to intra-myocardial injections of MSC or placebo, respectively. The primary endpoint was change in left ventricular end-systolic volume (LVESV), measured...

  10. Association between Platelet Counts before and during Pharmacological Therapy for Patent Ductus Arteriosus and Treatment Failure in Preterm Infants

    Directory of Open Access Journals (Sweden)

    Hannes Sallmon

    2018-03-01

    Full Text Available BackgroundThe role of platelets for mediating closure of the ductus arteriosus in human preterm infants is controversial. Especially, the effect of low platelet counts on pharmacological treatment failure is still unclear.MethodsIn this retrospective study of 471 preterm infants [<1,500 g birth weight (BW], who were treated for a patent ductus arteriosus (PDA with indomethacin or ibuprofen, we investigated whether platelet counts before or during pharmacological treatment had an impact on the successful closure of a hemodynamically significant PDA. The effects of other factors, such as sepsis, preeclampsia, gestational age, BW, and gender, were also evaluated.ResultsPlatelet counts before initiation of pharmacological PDA treatment did not differ between infants with later treatment success or failure. However, we found significant associations between low platelet counts during pharmacological PDA therapy and treatment failure (p < 0.05. Receiver operating characteristic (ROC curve analysis showed that platelet counts after the first, and before and after the second cyclooxygenase inhibitor (COXI cycle were significantly associated with treatment failure (area under the curve of >0.6. However, ROC curve analysis did not reveal a specific platelet cutoff-value that could predict PDA treatment failure. Multivariate logistic regression analysis showed that lower platelet counts, a lower BW, and preeclampsia were independently associated with COXI treatment failure.ConclusionWe provide further evidence for an association between low platelet counts during pharmacological therapy for symptomatic PDA and treatment failure, while platelet counts before initiation of therapy did not affect treatment outcome.

  11. Bed rest and increased diuretic treatment in chronic congestive heart failure

    DEFF Research Database (Denmark)

    Abildgaard, U; Aldershvile, J; Ring-Larsen, H

    1985-01-01

    To elucidate the effect of bed rest used as an adjunct to increased diuretic treatment, twelve patients with chronic congestive heart failure (CHF) had a 50% increase in loop diuretic dosage and were allocated to either continuous bed rest or bed rest during nights only. The 24-hour bed rest group...... is a reasonable adjunct to diuretic treatment in patients with CHF....

  12. [Endodontically treated teeth. Success--failure. Endorestorative treatment plan].

    Science.gov (United States)

    Zabalegui, B

    1990-01-01

    More and more often the general dentist is finding the presence of endodontically treated teeth during his treatment planning procedure. He has to ask himself if the endo-treated tooth functions and will continue to function function successfully, when deciding which final endo-restorative procedure to apply. For this reason the dentist or the endodontist with whom he works should clinically evaluate these teeth, establish a diagnostic criteria of their success or failure and a treatment plan according to the prognosis. The purpose of this article is to offer an organized clinical view of the steps to follow when evaluating an endodontically treated tooth and how to establish a final endo-restorative plan.

  13. TREATMENT FOR CHRONIC HEART FAILURE IN ELDERLY SUBJECTS

    Directory of Open Access Journals (Sweden)

    A. S. Poskrebysheva

    2014-07-01

    Full Text Available The treatment of chronic heart failure (CHF in patients over 60 years of age may be a challenge to a general practitioner. The physiological features of the elderly and significant comorbidity frequently have a considerable impact on the effects of drugs and the magnitude of side effects. Reduced sinus node automatism, significant atherosclerosis of the aorta and great vessels, and renal dysfunction - all should be borne in mind when choosing a drug and its dosage regimen. The paper considers non-drug treatment modalities, as well as the specific features of use of some groups of drugs and therapy for concomitant diseases in elderly patients with CHF.

  14. Effects of dopaminergic drug treatments on in vivo radioligand binding to brain vesicular monoamine transporters

    Energy Technology Data Exchange (ETDEWEB)

    Kilbourn, Michael R; Frey, Kirk A; Vander Borght, Thierry; Sherman, Phillip S

    1996-05-01

    The effects of various dopaminergic drug treatments on the in vivo regional brain distribution of high-affinity radioligands ([{sup 11}C]dihydrotetrabenazine and [{sup 11}C]methoxytetrabenazine) for the rat brain vesicular monoamine transporter (VMAT2) were determined. Acute treatments with reserpine (2 mg/kg i.p.), tetrabenazine (10 mg/kg i.v.) or related benzoisoquinolines significantly reduced radiotracer binding in vivo. In contrast, radiotracer distributions remained unchanged after treatments with other dopaminergic drugs, whether given by single injection (haloperidol, 1 mg/kg i.p., pargyline 80 mg/kg), repeatedly (pargyline, 80 mg/kg s.c., 14 days), or by continuous infusion (deprenyl, 10 mg/kg/day, 5 days; L-DOPA methyl ester 100 mg/kg/day, 5 days). Repeated injections of tetrabenazine (5 mg/kg i.p., twice daily, 3 days) did not alter in vivo radioligand binding measured after allowing drug washout from the brain. These studies support the proposal that in vivo PET imaging of VMAT2 radioligands in patients with extrapyramidal movement disorders will not be affected by concurrent use of L-DOPA or deprenyl.

  15. Background characteristics and treatment-related factors associated with treatment success or failure in a non-pharmacological intervention for dementia caregivers.

    Science.gov (United States)

    Rose, Karen C; Gitlin, Laura N

    2017-06-01

    Non-pharmacological interventions for persons with dementia often rely on family caregivers for implementation. However, caregivers differ in their readiness to use strategies. This study examines dyadic characteristics and treatment-related mechanisms associated with treatment success (high readiness to use strategies) and failure (low readiness to use strategies) at the conclusion of the Advancing Caregiver Training (ACT) intervention. Caregiver and person with dementia characteristics and treatment-related variables (treatment participation, number and type of strategies introduced and enacted) were examined in 110 caregivers in intervention. Interventionists rated readiness (1=precontemplation; 2=contemplation; 3=preparation; 4=action) of caregivers to use strategies at the final ACT session. Univariate analyses examined dyadic characteristics, and Multiple Analysis of Covariance (MANCOVA) and Analyses of Covariance (ANCOVA) examined treatment-related factors associated with readiness to use strategies at treatment completion. At treatment completion, 28.2% (N=31) scored in pre-action and 71.8% (N=79) at action. Caregivers at pre-action readiness levels were more likely than those at action to be a spouse, report greater financial difficulties and be managing fewer problem behaviors. Although both groups were introduced an equivalent number of non-pharmacological strategies, caregivers at pre-action were less likely than those at action to report enacting strategies. Certain dyadic characteristics and treatment-related factors were associated with treatment failure including financial strain and lack of strategy integration. Findings suggest that developing intervention components to address financial concerns and increase opportunities for practicing strategies and then using them between treatment sessions may be important for caregivers at risk of treatment failure.

  16. Association between Platelet Counts before and during Pharmacological Therapy for Patent Ductus Arteriosus and Treatment Failure in Preterm Infants.

    Science.gov (United States)

    Sallmon, Hannes; Weber, Sven C; Dirks, Juliane; Schiffer, Tamara; Klippstein, Tamara; Stein, Anja; Felderhoff-Müser, Ursula; Metze, Boris; Hansmann, Georg; Bührer, Christoph; Cremer, Malte; Koehne, Petra

    2018-01-01

    The role of platelets for mediating closure of the ductus arteriosus in human preterm infants is controversial. Especially, the effect of low platelet counts on pharmacological treatment failure is still unclear. In this retrospective study of 471 preterm infants [0.6). However, ROC curve analysis did not reveal a specific platelet cutoff-value that could predict PDA treatment failure. Multivariate logistic regression analysis showed that lower platelet counts, a lower BW, and preeclampsia were independently associated with COXI treatment failure. We provide further evidence for an association between low platelet counts during pharmacological therapy for symptomatic PDA and treatment failure, while platelet counts before initiation of therapy did not affect treatment outcome.

  17. The Correlation of Initial Sputum Smear Positivity on Treatment Failure of Category 1 Therapy for Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    Puput Dyah Ayu

    2016-11-01

    Full Text Available Tuberculosis is an infectious disease and is an important public health problem. Based on data from East Java Province Health Department reported that number of tuberculosis patient in Surabaya is the highest in East Java on year 2014. Early identification and good treatment based on the result of sputum identification are the strategy use to control tuberculosis widespread. So that why, microscopic observation to identify acid fast bacilli (AFB is the fundamental stage to determine recovery treatment. Initial sputum smear positivity is necessary to determine infectious graded. The objectives of the study were to identify of initial sputum smear positivity on treatment failure of category 1 therapy for pulmonary tuberculosis in RS Paru Surabaya year 2011-2014. This study used case control method with quantitative approach. Forty two samples were taken from secondary data. Case group is 21 samples who have treatment failure and control group is 21 successful treatment. Samples were selected by simple random sampling. The chi square correlation showed that highly positive initial smear (p = 0,045; OR = 5,4 have correlated and risk factor to treatment failure on category 1 therapy for pulmonary tuberculosis. The conclusion is patient’s high positive sputum smear initially correlated to treatment failure on category 1 therapy for pulmonary tuberculosis in RS Paru Surabaya year 2011–2014. Keywords: initial sputum smear positivity, treatment failure,, category 1 therapy for pulmonary tuberculosis

  18. How and why of orthodontic bond failures: An in vivo study

    Directory of Open Access Journals (Sweden)

    R K Vijayakumar

    2014-01-01

    Full Text Available Introduction: The bonding of orthodontic brackets and their failure rates by both direct and in-direct procedures are well-documented in orthodontic literature. Over the years different adhesive materials and various indirect bonding transfer procedures have been compared and evaluated for bond failure rates. The aim of our study is to highlight the use of a simple, inexpensive and ease of manipulation of a single thermo-plastic transfer tray and the use the of a single light cure adhesive to evaluate the bond failure rates in clinical situations. Materials and Methods: A total of 30 patients were randomly divided into two groups (Group A and Group B. A split-mouth study design was used, for, both the groups so that they were distributed equally with-out bias. After initial prophylaxis, both the procedures were done as per manufactures instructions. All patients were initially motivated and reviewed for bond failures rates for 6 months. Results: Bond failure rates were assessed for over-all direct and indirect procedures, anterior and posterior arches, and for individual tooth. Z-test was used for statistically analyzing, the normal distribution of the sample in a spilt mouth study. The results of the two groups were compared and P value was calculated using Z-proportion test to assess the significance of the bond failure. Conclusion: Over-all bond failure was more for direct bonding. Anterior bracket failure was more in-direct bonding than indirect procedure, which showed more posterior bracket failures. In individual tooth bond failure, mandibular incisor, and premolar brackets showed more failure, followed by maxillary premolars and canines.

  19. Time-to-Furosemide Treatment and Mortality in Patients Hospitalized With Acute Heart Failure

    NARCIS (Netherlands)

    Matsue, Yuya; Damman, Kevin; Voors, Adriaan A.; Kagiyama, Nobuyuki; Yamaguchi, Tetsuo; Kuroda, Shunsuke; Okumura, Takahiro; Kida, Keisuke; Mizuno, Atsushi; Oishi, Shogo; Inuzuka, Yasutaka; Akiyama, Eiichi; Matsukawa, Ryuichi; Kato, Kota; Suzuki, Satoshi; Naruke, Takashi; Yoshioka, Kenji; Miyoshi, Tatsuya; Baba, Yuichi; Yamamoto, Masayoshi; Murai, Koji; Mizutani, Kazuo; Yoshida, Kazuki; Kitai, Takeshi

    2017-01-01

    BACKGROUND Acute heart failure (AHF) is a life-threatening disease requiring urgent treatment, including a recommendation for immediate initiation of loop diuretics. OBJECTIVES The authors prospectively evaluated the association between time-to-diuretic treatment and clinical outcome. METHODS

  20. Tritium Waste Treatment System component failure data analysis from June 18, 1984--December 31, 1989

    International Nuclear Information System (INIS)

    Cadwallader, L.C.; Stolpe Gavett, M.A.

    1990-09-01

    This document gives the failure rates for the major tritium-bearing components in the Tritium Waste Treatment System at the Tritium Systems Test Assembly, which is a fusion research and technology facility at the Los Alamos National Laboratory. The failure reports, component populations, and operating demands/hours are given in this report, and sample calculations for binomial demand failure rates and poisson hourly failure rates are given in the appendices. The failure rates for tritium-bearing components were on the order of the screening failure rate values suggested for fusion reliability and risk analyses. More effort should be directed toward collecting and analyzing fusion component failure data, since accurate failure rates are necessary to refine reliability and risk analyses. 15 refs., 4 figs., 4 tabs

  1. First-drug treatment failures in 42 Turkish children with idiopathic childhood occipital epilepsies

    Directory of Open Access Journals (Sweden)

    Faruk Incecik

    2015-01-01

    Full Text Available Background: The early and late benign occipital epilepsies of childhood (BOEC are described as two discrete electro-clinical syndromes, eponymously known as Panayiotopoulos and Gastaut syndromes. The purpose of this study was to identify predictors of failure to respond to the initial antiepileptic drug (AED. Materials and Methods: A total of 42 children with BOEC were enrolled. Predictive factors were analyzed by survival methods. Results: Among the 42, 25 patients (59.5% were boys and 17 (40.5% were girls and the mean age at the seizure onset was 7.46 ± 2.65 years (4-14 years. Of the 42 patients, 34 (81.0% were treated relatively successfully with the first AED treatment, and 8 (19.0% were not responded initial AED treatment. There was no correlation between response to initial AED treatment and sex, consanguinity, epilepsy history of family, age of seizure onset, frequency of seizures, history of status epilepticus, duration of starting first treatment, findings on electroencephalogram. However, history of febrile seizure and type of BOEC were significantly associated with failure risk. Conclusions: Factors predicting failure to respond to the AED were history of febrile seizure and type of BOEC in children with BOEC.

  2. [Position of diuretics in the treatment of heart failure in light of current guidelines].

    Science.gov (United States)

    Bury, Krzysztof; Nessler, Jadwiga

    Diuretics are the longest-used drugs in heart failure after digoxin. This is due to their effect on the retention of sodium and an increase in the volume of fluid in the extracellular space secondary to neurohormonal and hemodynamic disorders occurs in heart failure, and their effectiveness in the treatment of symptomatic heart failure. Discontinuation of treatment with diuretics or use them in too small doses is one of the causes of exacerbation or acute heart failure.The effectiveness of most of diuretics does not confirm in the clinical trials, and the indications for their use are often based only on expert opinion. The effect of these drugs on morbidity and mortality in patients with HF was not examined. Diuretics reduce shortness of breath and swelling. For this reasons it is recom-mended to use them in patients with signs and symptoms of fluid retention regardless of the left ventricular ejection fraction.

  3. Clinical observation on the treatment of acute liver failure by combined non-biological artificial liver.

    Science.gov (United States)

    Li, Maoqin; Sun, Jingxi; Li, Jiaqiong; Shi, Zaixiang; Xu, Jiyuan; Lu, Bo; Cheng, Shuli; Xu, Yanjun; Wang, Xiaomeng; Zhang, Xianjiang

    2016-12-01

    The clinical efficacy and safety of different combinations of non-bio artificial liver in the treatment of acute liver failure was examined. A total of 61 cases were selected under blood purification treatment from the patients with severe acute liver failure admitted to the severe disease department of the hospital from December, 2010 to December, 2015. Three types of artificial liver combinations were observed, i.e., plasma exchange plus hemoperfusion plus continuous venovenous hemodiafiltration (PE+HP+CVVHDF), PE+CVVHDF and HP+CVVHDF. The heart rate (HR), mean arterial pressure (MAP), respiratory index (PaO 2 /FiO 2 ), liver and kidney function indicator, as well as platelet and coagulation function were compared. A comparison before and after the treatment using the three methods, showed improvement in the HRs, MAPs, PaO 2 /FiO 2 , total bilirubins (TBIL) and alanine aminotransferases (ALT) (Prate of 62.3% (38/61), and a viral survival rate of 35.0% (7/20); with the non-viral survival rate being 75.6% (31/41). In conclusion, following the treatment of three types of artificial livers, the function was improved to varying degrees, with the PE+HP+CVVHDF and the PE+CVVHDF method being better. By contrast, after the treatment of non-viral liver failure, the survival rate was significantly higher than the patients with viral liver failure.

  4. The causes, consequences, and treatment of left or right heart failure

    Directory of Open Access Journals (Sweden)

    Peteiro J

    2011-04-01

    Full Text Available Pablo Pazos-López, Jesús Peteiro-Vázquez, Ana Carcía-Campos, Lourdes García-Bueno, Juan Pablo Abugattas de Torres, Alfonso Castro-BeirasDepartment of Cardiology, Complejo hospitalario Universitario A Coruña, A Coruña, SpainAbstract: Chronic heart failure (HF is a cardiovascular disease of cardinal importance because of several factors: a an increasing occurrence due to the aging of the population, primary and secondary prevention of cardiovascular events, and modern advances in therapy, b a bad prognosis: around 65% of patients are dead within 5 years of diagnosis, c a high economic cost: HF accounts for 1% to 2% of total health care expenditure. This review focuses on the main causes, consequences in terms of morbidity, mortality and costs and treatment of HF.Keywords: heart failure, cause, consequence, treatment

  5. Adherence to the ESC Heart Failure Treatment Guidelines in Spain: ESC Heart Failure Long-term Registry.

    Science.gov (United States)

    Crespo-Leiro, María G; Segovia-Cubero, Javier; González-Costello, José; Bayes-Genis, Antoni; López-Fernández, Silvia; Roig, Eulàlia; Sanz-Julve, Marisa; Fernández-Vivancos, Carla; de Mora-Martín, Manuel; García-Pinilla, José Manuel; Varela-Román, Alfonso; Almenar-Bonet, Luis; Lara-Padrón, Antonio; de la Fuente-Galán, Luis; Delgado-Jiménez, Juan

    2015-09-01

    To estimate the percentage of heart failure patients in Spain that received the European Society of Cardiology recommended treatments, and in those that did not, to determine the reasons why. The study included 2834 consecutive ambulatory patients with heart failure from 27 Spanish hospitals. We recorded general information, the treatment indicated, and the reasons why it was not prescribed in some cases. In patients who met the criteria to receive a certain drug, true undertreatment was defined as the percentage of patients who, without justification, did not receive the drug. In total, 92.6% of ambulatory patients with low ejection fraction received angiotensin converting enzyme inhibitors or angiotensin receptor blockers, 93.3% beta-blockers, and 74.5% mineralocorticoid receptor antagonists. The true undertreatment rates were 3.4%, 1.8%, and 19.0%, respectively. Target doses were reached in 16.2% of patients receiving angiotensin converting enzyme inhibitors, 23.3% of those with angiotensin receptor blockers, 13.2% of those prescribed beta-blockers, and 23.5% of those with mineralocorticoid receptor antagonists. Among patients who could benefit from ivabradine, 29.1% received this drug. In total, 36% of patients met the criteria for defibrillator implantation and 90% of them had received the device or were scheduled for implantation, whereas 19.6% fulfilled the criteria for resynchronization therapy and 88.0% already had or would soon have the device. In patients who met the criteria, but did not undergo device implantation, the reasons were not cost-related. When justified reasons for not administering heart failure drugs were taken into account, adherence to the guideline recommendations was excellent. Exclusive use of the percentage of treated patients is a poor indicator of the quality of healthcare in heart failure. Measures should be taken to improve the attainment of optimal dosing in each patient. Copyright © 2015 Sociedad Española de Cardiolog

  6. A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier

    NARCIS (Netherlands)

    Hendrikse, NH; de Vries, EGE; Eriks-Fluks, L; van der Graaf, WTA; Hospers, GAP; Willemsen, ATM; Vaalburg, W; Franssen, EJF

    1999-01-01

    Drug resistance is a major cause of chemotherapy failure in cancer treatment, One reason is the overexpression of the drug efflux pump P-glycoprotein (P-gp), involved in multidrug resistance (MDR), In vivo pharmacokinetic analysis of P-gp transport might identify the capacity of modulation by P-gp

  7. The psychological impact of IVF failure after two or more cycles of IVF with a mild versus standard treatment strategy

    OpenAIRE

    Klerk, Cora; Macklon, Nick; Heijnen, E.M.; Eijkemans, René; Fauser, Bart; Passchier, Jan; Hunfeld, Joke

    2007-01-01

    textabstractBackground: Failure of IVF treatment after a number of cycles can be devastating for couples. Although mild IVF strategies reduce the psychological burden of treatment, failure may cause feelings of regret that a more aggressive approach, including the transfer of two embryos, was not employed. In this study, the impact of treatment failure after two or more cycles on stress was studied, following treatment with a mild versus a standard treatment strategy. Methods: Randomized cont...

  8. [Comparative effectiveness of different treatment methods of liver failure].

    Science.gov (United States)

    Kutepov, D E; Vershinina, M G; Pasechnik, I N; Sal'nikov, P S

    2014-01-01

    It was analyzed the results of treatment of 217 patients (139 men, 78 women) with chronic liver failure in case of liver cirrhosis of various etiology for study of degree of hepatic encephalopathyregression. All patients were divided into 3 groups. In the first group the drug therapy was used. In the second group additionallyplasma exchange was performed, in the third group - alsomolecular absorbent recirculating system was used (effectiveness of MARS-therapy).The results showed that the use of extracorporeal treatment techniques can effectively reduce the severity of hepatic encephalopathy in patients with liver cirrhosis. MARS-therapy improved the neurological status of patientsmore significantly in this case. It is considered that the inclusion of MARS-therapy in the combined treatment of patients leads to a significant reduction of hepatic encephalopathyseverity (1-2 points), in comparison with other methods of treatment.

  9. Role of Peritoneal Ultrafiltration in Heart Failure Treatment

    Directory of Open Access Journals (Sweden)

    Tuba Elif Şenel

    2017-09-01

    Full Text Available Cardiorenal syndrome (CRS is a general term that can reflect different clinical conditions in which cardiac and renal dysfunctions coexist. The main pathogenetic mechanisms playing a role in heart failure (HF and CRS are neurohumoral adaptation, right ventricular dilatation and dysfunction and systemic inflammation. Persistence of these factors cause focal and segmental glomerulosclerosis, and tubulointerstitial fibrosis in the renal parenchyma. Diuretics, beta blockers, renin-angiotensin-aldosterone system inhibitors, and vasodilators are the main medical treatments besides conventional approach, such as salt and water restriction and quitting smoking, in HF treatment. Diuretic resistance is the main problem emerging during diuretic treatments. Two renal replacement treatments have become prominent for removal of excess fluids via ultrafiltration in HF patients with diuretic resistance extracorporeal ultrafiltration with hemodialysis and peritoneal dialysis (PD. Herein, the role of these two ultrafiltration modalities, especially peritoneal ultrafiltration (PUF in the treatment of HF is discussed. The main studies and advantages of PUF in HF treatment were discussed. Moreover, effects of PD on glomerular filtration rate, hospitalization and mortality were investigated. In conclusion, PD is an alternative cheap, practical and convenient therapy in reducing cardiac volume burden in HF patients who do not respond well to standard treatments and/or require frequent hospitalization.

  10. [Prognostic factors related to non surgical treatment failure of splenic injuries in the abdominal blunt trauma].

    Science.gov (United States)

    Carvalho, Fábio Henrique de; Romeiro, Paula Christina Marra; Collaço, Iwan Augusto; Baretta, Giorgio Alfredo Pedroso; Freitas, Alexandre Coutinho Teixeira de; Matias, Jorge Eduardo Fouto

    2009-04-01

    Identify prognostic factors related to treatment failure of blunt splenic injuries managed by non surgical treatment (NST). Fifty six adult patients submitted to NST were prospectively studied. The injuries were diagnosed by computed axial tomography scan and classified according to AAST (American Association for Surgery of Trauma) criteria. Patients were divided in success and failure groups. NST failure was defined as the need for laparotomy for any reason. NST failures (19.6%) were due to: abdominal pain (45.4%), hemodinamic instability (36.4%), splenic haematoma associated to a fall in hematocrit (9.1%) and splenic abscess (9.1%). There were no failures in grade I and II of the splenic injuries; failure rate was 17.5% in grade III and IV injuries grouped, and 80% in grade V injuries (p = 0,0008). In the success group, 31.3% patients received red cell transfusions, versus 63.6% patients in the failure group (p = 0,05). Failure rate in patients with ISS = 8 was zero; 15.9% in patients with ISS 9 to 25; and 50% in patients with ISS = 26 (p = 0,05). There were no deaths or missed bowel injuries. ISS and splenic injury grade were related to failure of NST.

  11. Management of Ventriculoperitoneal Shunt Infections in Adults: Analysis of Risk Factors Associated With Treatment Failure.

    Science.gov (United States)

    Pelegrín, Iván; Lora-Tamayo, Jaime; Gómez-Junyent, Joan; Sabé, Nuria; García-Somoza, Dolors; Gabarrós, Andreu; Ariza, Javier; Viladrich, Pedro Fernández; Cabellos, Carmen

    2017-04-15

    Little is known regarding the optimal treatment of ventriculoperitoneal (VP) shunt infections in adults. Our aim was to assess the efficacy of treatment strategies and to identify factors that predict failure. Retrospective, observational study of patients aged ≥12 years with VP shunt infections (1980 -2014). Therapeutic approaches were classified under 4 headings: only antibiotics (OA), one-stage shunt replacement (OSSR), two-stage shunt replacement (TSSR), and shunt removal without replacement (SR). The primary endpoint was failure of the treatment strategy, defined as the absence of definite cerebrospinal fluid (CSF) sterilization or related mortality. The parameters that predicted failure were analyzed using logistic regression. Of 108 episodes (51% male, median age 50 years), 86 were analyzed. Intravenous antibiotics were administered for a median of 19 days. Eighty episodes were treated using strategies that combined antibiotic and surgical treatment (37 TSSR, 24 SR, 19 OSSR) and 6 with OA. Failure occurred in 30% of episodes, mostly due to lack of CSF sterilization in OSSR and OA groups. Twelve percent died of related causes and 10% presented superinfection of the CSF temporary drainage/externalized peritoneal catheter. TSSR was the most effective strategy when VP shunt replacement was attempted. The only independent risk factor that predicted failure was retention of the VP shunt, regardless of the strategy. This is the largest series of VP shunt infections in adults reported to date. VP shunt removal, particularly TSSR when the patient is shunt dependent, remains the optimal choice of treatment and does not increase morbidity. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  12. Premature thermal fatigue failure of aluminium injection dies with duplex surface treatment

    International Nuclear Information System (INIS)

    Corujeira Gallo, S.; Figueroa, Carlos A.; Baumvol, Israel J.R.

    2010-01-01

    Research highlights: → The premature failure of an aluminium injection die with a duplex surface treatment (plasma nitriding and physical vapor deposition coating) was investigated. → The origin of failure was attributed to the sulfur inclusions introduced into the surface of the tool by a sulfur-impregnated grinding stone used in the final polishing operation. → The low adhesion of the CrN coating on the sulfur inclusions led to the spalling of the coating, the exposure of the substrate material and the nucleation of cracks. → New evidence is presented on the influence of surface preparation and manufacturing processes on aluminium injection tool performance. - Abstract: The premature failure of an aluminium injection die with a duplex surface treatment (plasma nitriding and physical vapor deposition coating) was investigated, in an effort to identify the causes of such premature failure of the component. The manufacturing and the operating conditions were documented. Analytical tools were used, including scanning electron microscopy with energy dispersive X-ray capability, X-ray diffraction, and instrumented microhardness testing. Preliminary observations showed a microstructure of coarse tempered martensite, and a considerably rough surface with porosity and cracks. A detailed analysis of crack initiation sites identified sulfur inclusions in the subsurface, underneath the coating. A further revision of the processing conditions revealed that a sulfur-impregnated grinding stone had been used to polish the die. The chemical composition of such grinding stone matched that of the inclusions found in the subsurface of the failed component. Thus, searched causes of premature failure could be discussed on the lights of the present findings.

  13. In vivo dosimetry with semiconductor and thermoluminescent detectors applied to head and neck cancer treatment

    International Nuclear Information System (INIS)

    Viegas, Claudio Castelo Branco

    2003-03-01

    In vivo dosimetry in radiotherapy, i. e, the assessment of the doses received by patients during their treatments, permits a verification of the therapy quality. A routine of in vivo dosimetry is, undoubtedly, a direct benefit for the patient. Unfortunately, in Brazil and in Latin America this procedure is still a privilege for only a few patients. This routine is of common application only in developed countries. The aim of this work is to show the viability and implementation of a routine in vivo dosimetry, using diodes semiconductors and thermoluminescent dosimeters (TLD), at the radiotherapy section of the National Institute of Cancer in Brazil, in the case of head and neck cancer treatment. In order to reach that aim, the characteristics of the response of diodes ISORAD-p and LiF:Mg;Ti (TLD-100) thermoluminescent detectors in powder form were determined. The performance of those detectors for in vivo dosimetry was tested using an RANDO Alderson anthropomorfic phantom and, once their adequacy proved for the kind of measurements proposed, they were used for dose assessment in the case of tumour treatments in the head and neck regions, for Cobalt-60 irradiations. (author)

  14. An atypical presentation of mechanical failure of eruption of a mandibular permanent molar: diagnosis and treatment case report.

    LENUS (Irish Health Repository)

    Smith, C P

    2012-06-01

    Failure of eruption of mandibular permanent molars occurs infrequently but is a difficult clinical problem. It can be due to local or systemic factors or failure of the eruption process. Primary failure of eruption (PFE) is a rare condition that can result in severe posterior open bite, requires complex treatment strategies and has unfavourable outcomes. Mechanical failure of eruption (MFE) is more unusual but can respond positively to treatment. Differentiating between the two is crucial in making the correct diagnosis and managing the case successfully.

  15. Antibiotic resistance of Streptococcus pneumoniae in children with acute otitis media treatment failure.

    Science.gov (United States)

    Zielnik-Jurkiewicz, Beata; Bielicka, Anna

    2015-12-01

    The emergence of antibiotic-resistant bacteria is a major cause of treatment failure in children with acute otitis media (AOM). This study aimed to analyze the types of bacterial strains in fluid isolated from the middle ear of children with AOM who did not respond to oral antibiotic treatment. We also determined the antibiotic resistance of the most frequently isolated bacterial strain (Streptococcus pneumoniae) found in these children. This was a prospective study of 157 children with AOM aged from 6 months to 7 years admitted due to unsuccessful oral antibiotic treatment. All children underwent a myringotomy, and samples of the middle ear fluid were collected for bacteriological examination. Positive bacterial cultures were obtained in 104 patients (66.2%), with Streptococcus pneumoniae (39.69%), Haemophilus influenzae (16.03%) Staphylococcus aureus (16.03%), Staphylococcus haemolyticus (6.9%) and Streptococcus pyogenes (5.34%) found most frequently. The majority (65.4%) of S. pneumoniae strains were penicillin-intermediate-resistant or penicillin-resistant, and 67.2% strains of S. pneumoniae were multidrug-resistant. We identified S. pneumoniae as the most frequently isolated pathogen from the middle ear in children with AOM treatment failure and determined that the majority of strains were antibiotic-resistant. We propose that the microbiological identification of bacterial strains and their degree of antibiotic resistance should be performed prior to therapy in order to choose the most appropriate antibiotic therapy for children with AOM treatment failure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Morbidity from in-hospital complications is greater than treatment failure in patients with Staphylococcus aureus bacteraemia.

    Science.gov (United States)

    Holmes, Natasha E; Robinson, J Owen; van Hal, Sebastiaan J; Munckhof, Wendy J; Athan, Eugene; Korman, Tony M; Cheng, Allen C; Turnidge, John D; Johnson, Paul D R; Howden, Benjamin P

    2018-03-05

    Various studies have identified numerous factors associated with poor clinical outcomes in patients with Staphylococcus aureus bacteraemia (SAB). A new study was created to provide deeper insight into in-hospital complications and risk factors for treatment failure. Adult patients hospitalised with Staphylococcus aureus bacteraemia (SAB) were recruited prospectively into a multi-centre cohort. The primary outcome was treatment failure at 30 days (composite of all-cause mortality, persistent bacteraemia, or recurrent bacteraemia), and secondary measures included in-hospital complications and mortality at 6- and 12-months. Data were available for 222 patients recruited from February 2011 to December 2012. Treatment failure at 30-days was recorded in 14.4% of patients (30-day mortality 9.5%). Multivariable analysis predictors of treatment failure included age > 70 years, Pitt bacteraemia score ≥ 2, CRP at onset of SAB > 250 mg/L, and persistent fevers after SAB onset; serum albumin at onset of SAB, receipt of appropriate empiric treatment, recent healthcare attendance, and performing echocardiography were protective. 6-month and 12-month mortality were 19.1% and 24.2% respectively. 45% experienced at least one in-hospital complication, including nephrotoxicity in 19.5%. This study demonstrates significant improvements in 30-day outcomes in SAB in Australia. However, we have identified important areas to improve outcomes from SAB, particularly reducing renal dysfunction and in-hospital treatment-related complications.

  17. Parent Expectancies and Preferences for Mental Health Treatment: The Roles of Emotion Mind-Sets and Views of Failure.

    Science.gov (United States)

    Schleider, Jessica L; Weisz, John R

    2018-01-24

    Because parents are primary gatekeepers to mental health care for their children, parental expectations that mental health treatment is ineffective may undermine treatment seeking, retention, and response. Thus, a need exists to understand parents' expectations about treatment and to develop scalable interventions that can instill more favorable views. We examined parents' treatment expectancies and preferences for their offspring and themselves in relation to two global beliefs: mind-sets (malleability beliefs) of emotions and anxiety, and views of failure as enhancing versus debilitating. Study 1 (N = 200; 49.5% fathers; 70.4% Caucasian) examined associations among parents' emotion mind-sets, anxiety mind-sets, failure beliefs, and treatment expectancies and preferences. Study 2 (N = 430; 44.70% fathers; 75.80% Caucasian) tested whether online inductions teaching "growth emotion mind-sets" (viewing emotions as malleable), adaptive failure beliefs, or both improved parents' treatment expectancies and hypothetical preferences for treatment (vs. no-treatment). Participants received one of three 8- to 15-min inductions or a psychoeducation control, rating treatment expectancies. and preferences pre- and postinduction. In Study 1, fixed emotion mind-sets and failure-is-debilitating beliefs were associated with lower parent psychotherapy expectancies for offspring and themselves and stronger "no-treatment" preferences for offspring. In Study 2, inductions teaching (a) growth emotion mind-sets only and (b) growth emotion mind-sets and failure-is-enhancing beliefs improved parents' psychotherapy expectancies for themselves (ds = .38, .51) and offspring (ds = .30, .43). No induction increased parents' hypothetical preferences for treatment (vs. no-treatment). Findings suggest scalable strategies for strengthening parents' psychotherapy effectiveness beliefs for themselves and their children.

  18. Antiretroviral treatment interruptions induced by the Kenyan postelection crisis are associated with virological failure.

    Science.gov (United States)

    Mann, Marita; Diero, Lameck; Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W; Sidle, John; Buziba, Nathan; Kantor, Rami

    2013-10-01

    Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. We determined effects of unplanned TIs after the 2007-2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Unplanned conflict-related TIs are associated with increased likelihood of virological failure.

  19. Treatment of Gait Ignition Failure with Ropinirole

    Directory of Open Access Journals (Sweden)

    Alexis N. Cohen-Oram

    2014-10-01

    Full Text Available Gait ignition failure (GIF is a syndrome characterized by hesitation or inability to initiate gait from a static position. It may occur in a variety of conditions, including normal pressure hydrocephalus, subcortical vascular disease, parkinsonian syndromes and a variety of focal lesions. Previous information on the treatment of GIF has been primarily anecdotal, but there have been a few reports of response to dopamine agonists. We report a 63-year-old man with anoxic encephalopathy who developed GIF nine years after the initial anoxic insult. The patient’s GIF responded robustly, albeit transiently, to ropinirole. MRI was unrevealing, but a positron emission tomography scan showed hypometabolism in the deep frontal ACA/MCA watershed area; this may have disconnected the basal ganglia from the motor cortex and/or interrupted dopaminergic mesocortical transmission. Our understanding of the pathophysiology and the treatment of GIF remains limited, but there may be at least a limited therapeutic role for dopamine agonists.

  20. Incidence and risk factors of antiretroviral treatment failure in treatment-naïve HIV-infected patients at Chiang Mai University Hospital, Thailand

    Science.gov (United States)

    2011-01-01

    Background The use of combination antiretroviral therapy (cART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to cART are major obstacles for access to treatment especially in resource-limited settings. In this study, we aimed to determine the incidence and risk factors of treatment failure in a cohort of treatment-naïve Thai HIV-infected patients. Methods A retrospective cohort study was conducted among HIV-infected patients initiating their first cART at Chiang Mai University Hospital, Thailand. Results From January 2002 to December 2008, 788 patients were enrolled; 365 were male (46.3%), and the mean age was 37.9 ± 8.6 years. The median baseline CD4 count was 57.7 cells/mm3 (IQR 22, 127). GPO-VIR® (a fixed-dose combination of lamivudine, stavudine, and nevirapine) was the most common prescribed cART (657 patients, 83.4%). Seventy-six patients developed virological failure given the cumulative incidence of 9.6%. The incidence of virological failure was 2.79 (95% CI 2.47, 3.14) cases per 100 person years. Poor adherence was the strongest predictor for virological failure. Of 535 immunologically evaluable patients, 179 (33.5%) patients developed immunological failure. A low CD4 cell count at baseline (< 100 cells/mm3) and the increment of CD4 cell count of < 50 cell/mm3 after 6 months of cART were the predictors for immunological failure (p < 0.001). Conclusions This study demonstrated that even in resource-limited settings, the high rate of success could be expected in the cohort with good and sustainable drug adherence. Poor adherence, older age, and low baseline CD4 cell count are the predictors for unfavorable outcome of cART. PMID:22060823

  1. Treatment failures after antibiotic therapy of uncomplicated urinary tract infections

    DEFF Research Database (Denmark)

    Bjerrum, Lars; Dessau, Ram B; Hallas, Jesper

    2002-01-01

    OBJECTIVES: The efficacy of sulfamethizole and pivmecillinam in the treatment of urinary tract infections (UTI) has been questioned because of an increase in the prevalence of resistant strains. The aim of this study was to describe the risk of treatment failures over the last 10 years. DESIGN......: Retrospective cohort study. MATERIAL: Data were retrieved from Odense Pharmaco Epidemiological Database and consisted of women receiving sulfamethizole (n = 44,716) or pivmecillinam (n = 3093) during the period 1990-99. MAIN OUTCOME MEASURES: Prescription of a new antibiotic drug appropriate for UTI within 4...

  2. Premature ovarian failure/dysfunction following surgical treatment of polycystic ovarian syndrome: A case series

    Directory of Open Access Journals (Sweden)

    T.K. Al-Hussaini

    2017-09-01

    Full Text Available Polycystic ovarian syndrome (PCOS is one of the most common causes of infertility in women. Surgical treatment of PCOS, either by the antiquated wedge resection or ovarian drilling, is one of the commonly used lines in developing countries due to its low-cost. Premature ovarian failure and diminished ovarian reserve are serious complications of the surgical treatment but no published reports sufficiently highlighted these hazards. In this case series, we report on twenty one women aged between 19–39 years, presented to Infertility Clinic, Assiut Women Health Hospital with ovarian dysfunction, diagnosed within 6–36 months after surgical management of PCOS. Nineteen of them had laparoscopic bilateral ovarian drilling using electrocauterization, and the last two had bilateral wedge resection of the ovaries through minilaparotomy. Accurate and documented diagnosis of PCOS, appropriate surgical training, adjusted thermal injury and adjusted number of punctures are essential for the avoidance of excessive damage to the ovaries. Under treatment (failure of drilling is much better than premature ovarian failure or diminishing ovarian reserve.

  3. Minimizing treatment planning errors in proton therapy using failure mode and effects analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Yuanshui, E-mail: yuanshui.zheng@okc.procure.com [ProCure Proton Therapy Center, 5901 W Memorial Road, Oklahoma City, Oklahoma 73142 and Department of Physics, Oklahoma State University, Stillwater, Oklahoma 74078-3072 (United States); Johnson, Randall; Larson, Gary [ProCure Proton Therapy Center, 5901 W Memorial Road, Oklahoma City, Oklahoma 73142 (United States)

    2016-06-15

    Purpose: Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. Methods: The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authors estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. Results: In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. Conclusions: The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their

  4. Minimizing treatment planning errors in proton therapy using failure mode and effects analysis

    International Nuclear Information System (INIS)

    Zheng, Yuanshui; Johnson, Randall; Larson, Gary

    2016-01-01

    Purpose: Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. Methods: The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authors estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. Results: In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. Conclusions: The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their

  5. Recent advances in treatment of heart failure [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Takeshi Kitai

    2015-12-01

    Full Text Available With the total cases and economic burden of heart failure continuing to rise, there is an overwhelming need for novel therapies. Several drugs for heart failure have succeeded in preclinical and early-phase clinical trials, but most of them failed to show the real benefit in pivotal clinical trials. Meanwhile, the US Food and Drug Administration recently approved two promising new drugs to treat heart failure: ivabradine and sacubitril/valsartan. Furthermore, some of the newer agents in testing offer the potential for significant progress in addition to these drugs. Patiromer and zirconium cyclosilicate are attractive agents that are expected to prevent hyperkalemia during renin-angiotensin-aldosterone system inhibition, and serelaxin and urodilatin are promising drugs in the treatment of acute heart failure. Future clinical trials with more appropriate study designs, optimal clinical endpoints, and proper patient selection are mandatory to assess the true efficacy of these attractive compounds in clinical practice.

  6. Treatment with beta-blockers in nurse-led heart failure clinics

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Schou, Morten; Videbaek, Lars

    2007-01-01

    BACKGROUND: Beta-blockers (BBs) are a cornerstone in the treatment of chronic heart failure (HF), but several surveys have documented that many patients are not offered treatment or are not titrated to target doses. In part to address this problem, specialized, nurse-led HF clinics have been......% of the patients were being treated with a BB. Mean dose (relative to target dose) was 63 (+/-35)% in patients receiving a BB and target dose was reached by 21%. Patients who were not on BBs were more often female, elderly and in NYHA class III-IV. In a multivariable model only lower age predicted BB use at three...... months (PElderly patients appear to be less likely to receive treatment....

  7. HEART FAILURE – KEEPING STEP WITH THE PROGRESS

    Directory of Open Access Journals (Sweden)

    Camelia Diaconu

    2018-06-01

    countries across North America (NA, Central and South America (CSA, Western (WE and Eastern Europe (EE, the Eastern Mediterranean and Africa (EMA, South East Asia (SEA and the Western Pacific (WP, under the study co-chairs, Prof. Gerasimos Filippatos (Greece and Prof. Mihai Gheorghiade (USA. Inter-regional differences in the hospital entry point, comorbidities and precipitants have been observed. Ischemia was a common precipitant in SEA, WP and EMA, whereas non-adherence to diet and medication was more common in NA. There have been also observed differences regarding the treatment, especially in time to initial intravenous therapy. Patients in NA have significantly longer time to first therapy, compared with other regions; this may impact the symptoms, because the sooner the IV therapies are delivered, the sooner symptoms will improve. There are differences regarding the implementation of international heart failure guidelines, which may influence the patients’ outcomes. Researchers from the Institute of Molecular Biotechnology at the Vienna BioCenter have studied the first systems for heart regeneration following complex heart attacks in mammals. In vivo neonatal models showed that, after a heart attack, mice underwent total repair of cardiac injury. This type of repair had been encountered previously in fish, but not in mammals. The researchers set up now genetic systems to identify the molecular signals that mediate this regeneration of the heart. Biotechnologies may become the future of the heart failure treatment.

  8. SU-E-T-421: Failure Mode and Effects Analysis (FMEA) of Xoft Electronic Brachytherapy for the Treatment of Superficial Skin Cancers

    International Nuclear Information System (INIS)

    Hoisak, J; Manger, R; Dragojevic, I

    2015-01-01

    Purpose: To perform a failure mode and effects analysis (FMEA) of the process for treating superficial skin cancers with the Xoft Axxent electronic brachytherapy (eBx) system, given the recent introduction of expanded quality control (QC) initiatives at our institution. Methods: A process map was developed listing all steps in superficial treatments with Xoft eBx, from the initial patient consult to the completion of the treatment course. The process map guided the FMEA to identify the failure modes for each step in the treatment workflow and assign Risk Priority Numbers (RPN), calculated as the product of the failure mode’s probability of occurrence (O), severity (S) and lack of detectability (D). FMEA was done with and without the inclusion of recent QC initiatives such as increased staffing, physics oversight, standardized source calibration, treatment planning and documentation. The failure modes with the highest RPNs were identified and contrasted before and after introduction of the QC initiatives. Results: Based on the FMEA, the failure modes with the highest RPN were related to source calibration, treatment planning, and patient setup/treatment delivery (Fig. 1). The introduction of additional physics oversight, standardized planning and safety initiatives such as checklists and time-outs reduced the RPNs of these failure modes. High-risk failure modes that could be mitigated with improved hardware and software interlocks were identified. Conclusion: The FMEA analysis identified the steps in the treatment process presenting the highest risk. The introduction of enhanced QC initiatives mitigated the risk of some of these failure modes by decreasing their probability of occurrence and increasing their detectability. This analysis demonstrates the importance of well-designed QC policies, procedures and oversight in a Xoft eBx programme for treatment of superficial skin cancers. Unresolved high risk failure modes highlight the need for non-procedural quality

  9. Risk Factors for Asthma Exacerbation and Treatment Failure in Adults and Adolescents with Well-Controlled Asthma during Continuation and Step Down Therapy.

    Science.gov (United States)

    DiMango, Emily; Rogers, Linda; Reibman, Joan; Gerald, Lynn B; Brown, Mark; Sugar, Elizabeth A; Henderson, Robert; Holbrook, Janet T

    2018-06-04

    Although national and international guidelines recommend reduction of asthma controller therapy or 'step-down" therapy in patients with well controlled asthma, it is expected that some individuals may experience worsening of asthma symptoms or asthma exacerbations during step-down. Characteristics associated with subsequent exacerbations during step-down therapy have not been well defined. The effect of environmental tobacco smoke (ETS) exposure on risk of treatment failure during asthma step down therapy has not been reported. To identify baseline characteristics associated with treatment failure and asthma exacerbation during maintenance and guideline-based step-down therapy. The present analysis uses data collected from a completed randomized controlled trial of optimal step-down therapy in patients with well controlled asthma taking moderate dose combination inhaled corticosteroids/long acting beta agonists. Participants were 12 years or older with physician diagnosed asthma and were enrolled between December 2011 and May 2014. An Emergency Room visit in the previous year was predictive of a subsequent treatment failure (HR 1.53 (1.06, 2.21 CI). For every 10% increase in baseline forced expiratory volume in one second percent predicted, the hazard for treatment failure was reduced by 14% (95% CI: 0.74-0.99). There was no difference in risk of treatment failure between adults and children, nor did duration of asthma increase risk of treatment failure. Age of asthma onset was not associated with increased risk of treatment failure. Unexpected emergency room visit in the previous year was the only risk factor significantly associated with subsequent asthma exacerbations requiring systemic corticosteroids. Time to treatment failure or exacerbation did not differ in participants with and without self-report of ETS exposure. The present findings can help clinicians identify patients more likely to develop treatment failures and exacerbations and who may therefore

  10. In vivo dose verification for photon treatments of head and neck carcinomas using MOSFET dosimeters

    International Nuclear Information System (INIS)

    Tung, C.J.; Wang, L.C.; Wang, H.C.; Lee, C.C.; Chao, T.C.

    2008-01-01

    In vivo dosimetry was performed for the head and neck carcinoma patients during the treatment of a large photon field using MOSFETs. This study followed the protocols recommended by the European Society for Therapeutic Radiology and Oncology. A total of 32 portals belonging to 12 patients were under investigation. Results showed that the deviation between in vivo midline doses and planned target doses was partly due to the manual dose calculations in the treatment planning which used the patient geometric thickness rather than the radiological thickness. Other factors responsible for this deviation included the difficult positioning of MOSFETs on the face mask, the asymmetric positioning of MOSFETs on the left and right sides of the mask, and the asymmetric tissue inhomogeneities with respect to the body midline. To reduce the deviation contributed from these factors, in vivo midline doses were calculated by averaging the results for each bilaterally opposed portals and compared with corresponding planned target doses. This comparison showed that MOSFET dosimeters are suitable for in vivo dosimetry of the present study

  11. Methodical treatment of dependent failures in risk analyses

    International Nuclear Information System (INIS)

    Hennings, W.; Mertens, J.

    1987-06-01

    In this report the state-of-the-art regarding dependent failures is compiled and commented on. Among others the following recommendations are infered: The term 'common mode failures' should be restricted to failures of redundant, similar components; the generic term is 'dependent failures' with the subsets 'causal failures' and 'common cause failures'. In risk studies, dependent failures should be covered as far as possible by 'explicit methods'. Nevertheless an uncovered rest remains, which should be accounted for by sensitivity analyses using 'implicit methods'. For this the homogeneous Marshall-Olkin model is recommended. Because the available reports on operating experiences only record 'common mode failures' systematically, it is recommended to additionally apply other methods, e.g. carry out a 'precursor study'. (orig.) [de

  12. Lessons learned from vivo-morpholinos: How to avoid vivo-morpholino toxicity

    Science.gov (United States)

    Ferguson, David P.; Dangott, Lawrence J.; Lightfoot, J. Timothy

    2014-01-01

    Vivo-morpholinos are a promising tool for gene silencing. These oligonucleotide analogs transiently silence genes by blocking either translation or pre-mRNA splicing. Little to no toxicity has been reported for vivo-morpholino treatment. However, in a recent study conducted in our lab, treatment of mice with vivo-morpholinos resulted in high mortality rates. We hypothesized that the deaths were the result of oligonucleotide hybridization, causing an increased cationic charge associated with the dendrimer delivery moiety of the vivo-morpholino. The cationic charge increased blood clot formation in whole blood treated with vivo-morpholinos, suggesting that clotting could have caused cardiac arrest in the deceased mice. Therefore, we investigate the mechanism by which some vivo-morpholinos increase mortality rates and propose techniques to alleviate vivo-morpholino toxicity. PMID:24806225

  13. Failure of azithromycin 2.0 g in the treatment of gonococcal urethritis caused by high-level resistance in California.

    Science.gov (United States)

    Gose, Severin O; Soge, Olusegun O; Beebe, James L; Nguyen, Duylinh; Stoltey, Juliet E; Bauer, Heidi M

    2015-05-01

    We report a treatment failure to azithromycin 2.0 g caused by a urethral Neisseria gonorrhoeae isolate with high-level azithromycin resistance in California. This report describes the epidemiological case investigation and phenotypic and genetic characterization of the treatment failure isolate.

  14. First-line antiretroviral treatment failure and associated factors in HIV patients at the University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia.

    Science.gov (United States)

    Ayalew, Mohammed Biset; Kumilachew, Dawit; Belay, Assefa; Getu, Samson; Teju, Derso; Endale, Desalegn; Tsegaye, Yemisirach; Wale, Zebiba

    2016-01-01

    Antiretroviral therapy (ART) restores immune function and reduces HIV-related adverse outcomes. But treatment failure erodes this advantage and leads to an increased morbidity and compromised quality of life in HIV patients. The aim of this study was to determine the prevalence and factors associated with first-line ART failure in HIV patients at the University of Gondar Teaching Hospital. A retrospective study was conducted on 340 adults who had started ART during the period of September 2011 to May 2015. Data regarding patients' sociodemographics, baseline characteristics, and treatment-related information were collected through review of their medical charts. Data were analyzed using SPSS version 21. Descriptive statistics, cross-tabs, and binary and multiple logistic regressions were utilized. Pfailure. The median duration of treatment failure from initiation of treatment was 17.5 months (8-36 months). Poor adherence to treatment and low baseline CD4 cell count were found to be significant predictors of treatment failure. The prevalence of first-line ART failure was 4.1%. Treatment failure was most likely to occur for the patients who had poor drug adherence and those who were delayed to start ART till their CD4 cell count became very low (<100 cells/mm(3)).

  15. Advances in the treatment of acute liver failure

    Directory of Open Access Journals (Sweden)

    LUO Ling

    2018-02-01

    Full Text Available Acute liver failure (ALF is a rare life-threatening disease with rapid progression and a low survival rate and affects the function of multiple organ systems. Early identification of cause and protection of vital organs are critical for patients' survival. With the development in artificial liver, stem cell transplantation, and liver transplantation in recent years, the outcome of ALF has been greatly improved. This article elaborates on the treatment of ALF from the aspects of the etiology of ALF and major organ systems involved and introduces the latest advances in artificial liver and stem cell transplantation.

  16. Potential of resveratrol in the treatment of heart failure.

    Science.gov (United States)

    Raj, Pema; Louis, Xavier Lieben; Thandapilly, Sijo Joseph; Movahed, Ali; Zieroth, Shelley; Netticadan, Thomas

    2014-01-30

    The concept of food has expanded beyond its traditional role of survival and hunger satisfaction, to include a role in the prevention and treatment of disease. Polyphenols are classes of compounds that are synthesized by plants to serve a wide variety of functions including growth pollination and defense. These compounds have recently received increased attention in medical research. In this group, one of the most studied has been resveratrol (3,5,4,-trihydroxystilbene), a polyphenol, which is found predominantly in grapes and berries. Over the past two decades, researchers have studied the ability of resveratrol to prevent or reverse the development of abnormalities in heart structure and function in animal models of heart disease and heart failure. The results from animal studies have been promising, and very recently, this knowledge has been translated into examining the efficacy of resveratrol in humans with heart disease/failure. In this review we will discuss the current status of resveratrol research on cardioprotection. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor-Based Antiretroviral Therapy.

    Science.gov (United States)

    Suaysod, Rapeepan; Ngo-Giang-Huong, Nicole; Salvadori, Nicolas; Cressey, Tim R; Kanjanavanit, Suparat; Techakunakorn, Pornchai; Krikajornkitti, Sawitree; Srirojana, Sakulrat; Laomanit, Laddawan; Chalermpantmetagul, Suwalai; Lallemant, Marc; Le Cœur, Sophie; McIntosh, Kenneth; Traisathit, Patrinee; Jourdain, Gonzague

    2015-07-01

    Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure. HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure. A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P = .03), age >13 years (aHR, 2.9; P < .001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P = .03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P < .001). Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Detection of Taenia solium taeniasis coproantigen is an early indicator of treatment failure for taeniasis.

    Science.gov (United States)

    Bustos, Javier A; Rodriguez, Silvia; Jimenez, Juan A; Moyano, Luz M; Castillo, Yesenia; Ayvar, Viterbo; Allan, James C; Craig, Philip S; Gonzalez, Armando E; Gilman, Robert H; Tsang, Victor C W; Garcia, Hector H

    2012-04-01

    Taenia solium causes taeniasis and cysticercosis, a zoonotic complex associated with a significant burden of epilepsy in most countries. Reliable diagnosis and efficacious treatment of taeniasis are needed for disease control. Currently, cure can be confirmed only after a period of at least 1 month, by negative stool microscopy. This study assessed the performance of detection by a coproantigen enzyme-linked immunosorbent assay (CoAg-ELISA) for the early evaluation of the efficacy of antiparasitic treatment of human T. solium taeniasis. We followed 69 tapeworm carriers who received niclosamide as standard treatment. Stool samples were collected on days 1, 3, 7, 15, 30, and 90 after treatment and were processed by microscopy and CoAg-ELISA. The efficacy of niclosamide was 77.9% (53/68). Thirteen patients received a second course of treatment and completed the follow-up. CoAg-ELISA was therefore evaluated for a total of 81 cases (68 treatments, 13 retreatments). In successful treatments (n = 64), the proportion of patients who became negative by CoAg-ELISA was 62.5% after 3 days, 89.1% after 7 days, 96.9% after 15 days, and 100% after 30 days. In treatment failures (n = 17), the CoAg-ELISA result was positive for 70.6% of patients after 3 days, 94.1% after 7 days, and 100% after 15 and 30 days. Only 2 of 17 samples in cases of treatment failure became positive by microscopy by day 30. The presence of one scolex, but not multiple scolices, in posttreatment stools was strongly associated with cure (odds ratio [OR], 52.5; P taeniasis. Early assessment at day 15 would detect treatment failure before patients become infective.

  19. Successful treatment of 54 patients with acute renal failure after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Lei CHEN

    2015-06-01

    Full Text Available Objectives To evaluate the result of treatment of acute renal failure (ARF in patients after cardiac surgery. Methods The clinical data of 54 cases admitted to the hospital from Jan. 2004 to Jan. 2014 and suffered from ARF after cardiac surgery were retrospectively analyzed. Among 54 cases, there were 35 males and 19 females, aged from one month to 79 years with a median of 52 years. The surgical procedures included coronary artery bypass grafting (CABG, 10 cases, valve surgery (22 cases, combined CABG and valve surgery (4 cases, operation on aorta (14 case, and radical correction of Fallot tetralogy (4 cases. After the operations mentioned above, 50 patients received continuous renal replacement therapy (CRRT, and 4 patients received peritoneal dialysis. Results Nine patients died, the mortality rate was 16.7%. Exploratory hemostasis by thoracotomy was performed in 8 patients, and extubation failure occurred in 4 cases. Of the 9 non-survivors, 6 died from multiple organ failure (MOF, 2 died from cerebral hemorrhage, and one died from acute respiratory failure. Serum creatinine (SCr and blood urea nitrogen (BUN levels declined obviously after CRRT and peritoneal dialysis (P<0.05, and all the patients were shown to have stable hemodynamics in the course of treatment, and no hemorrhage or embolism occurred. Conclusions ARF after cardiac surgery should be detected early and treated in time. CRRT and peritoneal dialysis are safe, convenient and effective procedures, and may decrease the mortality rate in patients with ARF after cardiac surgery. DOI: 10.11855/j.issn.0557-7402.2015.04.13

  20. Management of treatment failure in restless legs syndrome (Willis-Ekbom disease).

    Science.gov (United States)

    Garcia-Borreguero, Diego; Cano-Pumarega, Irene; Marulanda, Rafael

    2018-01-09

    Dopaminergic drugs have been widely used over the last decades for the treatment of restless legs syndrome (RLS)/Willis-Ekbom disease (WED). While the majority of studies show an initial improvement in symptoms, longer studies and clinical experience show that either treatment efficacy decreases with time, and/or augmentation develops: dopaminergic augmentation has been reported to be the main reason for treatment discontinuation and treatment failure in RLS/WED. The current review discusses the main reasons for treatment failure in RLS/WED and outlines the most recent expert-based strategies to prevent and manage it. The main strategy for preventing augmentation is to consider non-dopaminergic medications such as α2δ ligands for initial RLS/WED treatment; these effective drugs have been shown to have little risk of augmentation. Alternatively, should dopaminergic drugs be elected as initial treatment, then the daily dose should be kept low and not exceed maximum recommended doses, however, it should be kept in mind that even low dose dopaminergics can cause augmentation. Patients with low iron stores should be given appropriate iron supplementation. Daily treatment should start only when symptoms significantly impact quality of life in terms of frequency and severity; while intermittent treatment might be considered in intermediate cases. Treatment of existing augmentation should be initiated, where possible, with the elimination/correction of extrinsic exacerbating factors (iron levels, antidepressants, antihistamines, etc.). In cases of mild augmentation, dopamine agonist therapy can continue by dividing or advancing the dose, or increasing the dose if there are breakthrough nighttime symptoms. Alternatively, the patient can be switched to an α2δ ligand or rotigotine. For severe augmentation, the patient can be switched to an α2δ ligand or rotigotine, noting that rotigotine may produce augmentation at higher doses with long-term use. In more severe cases

  1. Factors Associated with Treatment Failure among Smear Positive TB Patients in Khorasan-e-Razavi and Sistan-Baluchistan Provinces, Iran

    Directory of Open Access Journals (Sweden)

    Hekmatollah Khoubfekr, Narges Khanjani, Yunes Jahani, Mahmoud Moosazadeh

    2016-12-01

    Full Text Available Introduction: Tuberculosis (TB treatment failure is one of the major problems of the health sector in developing countries. Poor treatment of patients leads to drug resistance, relapse, death, and ultimately prevents TB control programs. This study was conducted to determine the factors affecting tuberculosis treatment failure in Khorasan and Sistan- Balochistan regions which have a high prevalence of TB. Methods: In this case - control study 270 patients with tuberculosis (90 cases, 180 controls were analyzed. New TB patients registered with failure to treatment according to the national protocol between March 2008 - March 2012 were chosen as cases and new TB patients with negative sputum smear in the same time frame were enrolled as control group. Demographic data and clinical treatment outcomes were collected through interviews and file records. Multivariate logistic regression analysis was used to determine the predictors of treatment failure in SPSS 19. Results: Independent factors and predictors of failure treatment included illiteracy, a three plus positive sputum smear, positive sputum smear at end of the second month, non-implementation of the Directly Observed Treatment Short strategy by healthcare staff, history of addiction and history of diabetes. Conclusion: Intervention programs for early detection and control of diabetes, drug control programs, giving priority to providing DOTS by health care workers, more individual care and attention to patients with initial smear p + 3 or those that remain sputum positive at the end of the second month or those who are less educated is necessary. J Microbiol Infect Dis 2016;6(4: 172-178

  2. A Treatment Program for Failure to Thrive: A Cost-Effectiveness Analysis.

    Science.gov (United States)

    Karniski, Walt; And Others

    1986-01-01

    Analysis of treatment of infants suffering from Failure to Thrive placed in foster medical placement homes (MPH, N=17) or admitted to hospitals (N=18) revealed that the MPH infants grew more than hospitalized infants and parents of MPH children had advantages of education and support. The MPH program cost less than 25 percent of hospital care.…

  3. How Successful is Non-Invasive Ventilation Treatment that is Initiated in the Emergency Department in Cases of COPD Exacerbations with Acute Hypercapnic Respiratory Failure? Can We Predict Treatment Failure?

    Directory of Open Access Journals (Sweden)

    Meltem Çoban Ağca

    2017-04-01

    Full Text Available Objective: We aimed to investigate the success rate of non-invasive ventilation (NIV in wards and the predictors of failure in cases of chronic obstructive pulmonary disease (COPD-related acute hypercapnic respiratory failure (AHRF. Methods: The was a retrospective study conducted in a tertiary teaching hospital between May 2011 and 2013. Patients who were admitted to the emergency department (ED because of COPD with AHRF were evaluated; 544 patients who initially received NIV in ED and were transferred to wards were included. Patient characteristics, baseline and follow-up pH values, and partial arterial carbon dioxide (PaCO2 values were recorded. Baseline pH values were categorized as severe (pH<7.26, moderate (pH≥7.26–7.30, and mild (pH≥7.30 acidosis. According to the in-hospital outcome, patients were classified in 2 groups: Group 1: home discharge, Group 2: death or intensive care unit transfer. Results: Treatment resulted in success in 477 (88% patients. Albumin levels were significantly low and the mean Charlson index (CI score was significantly high in Group 2. Admission pH and PaCO2 values did not affect the treatment outcome. Patients in Group 2 had higher PaCO2 and lower pH values as well as a lower level of decrease in PaCO2 values within 2 hours of treatment in ED. Similarly, higher PaCO2 and lower pH values at the end of the first day in wards were indicative of NIV failure (p<0.05. Conclusion: The success rate of NIV in wards in cases of AHRF is high. Patients with low albumin levels and higher CI scores have worse response to treatment. pH or PaCO2 values after a few hours of treatment and not the baseline pH or PaCO2 values are better predictors than the baseline pH and PaCO2 values.

  4. For the improvement of Heart Failure treatment in Portugal - Consensus statement.

    Science.gov (United States)

    Fonseca, Cândida; Brito, Dulce; Cernadas, Rui; Ferreira, Jorge; Franco, Fátima; Rodrigues, Teresa; Morais, João; Silva Cardoso, José

    2017-01-01

    Heart failure is a syndrome with high prevalence, morbidity and mortality, but awareness of the disease is poor among the general public and policy makers. This document, which was prepared by a group of experts consisting of cardiologists, internists and general practitioners, aims to set out in detail the problem of heart failure in Portugal at several levels: burden of the disease, diagnosis, treatment and monitoring. To this aim, different aspects of the management of the various stages of the disease are identified and discussed in detail, covering both outpatients and hospitalized patients. In order to optimize the medical care provided to these patients, various short-, medium- and long-term solutions and strategies are put forward that have the potential to improve the integration and use of available resources. The intention is to highlight strategies that are not based on a single model but can be adapted to different regional circumstances, in order to increase awareness and improve management of heart failure in Portugal. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. External beam radiation for retinoblastoma: Results, patterns of failure, and a proposal for treatment guidelines

    International Nuclear Information System (INIS)

    Hernandez, J. Carlos; Brady, Luther W.; Shields, Jerry A.; Shields, Carol L.; Potter, Patrick de; Karlsson, Ulf L.; Markoe, Arnold M.; Amendola, Beatriz E.; Singh, Arun

    1996-01-01

    Purpose: To analyze treatment results and patterns of failure following external beam radiation for retinoblastoma and propose treatment guidelines according to specific clinical variables. Methods and Materials: We analyzed 27 patients (34 eyes) with retinoblastoma who received external beam radiation as initial treatment at Hahnemann University Hospital from October 1980 to December 1991 and have been followed for at least 1 year. Of the 34 eyes, 14 were Groups I-II (Reese-Ellsworth classification), 7 were Group III, and 13 were Groups IV-V. Doses ranged from 34.5-49.5 Gy (mean 44.3 Gy, median 45 Gy) in 1.5-2.0 Gy fractions generally delivered through anterior and lateral wedged pair fields. Results: At a mean follow up of 35.2 months (range 12-93 months), local tumor control was obtained in 44% (15 out of 34) of eyes with external beam radiation alone. Salvage therapy (plaque brachytherapy, cryotherapy, and/or photocoagulation) controlled an additional 10 eyes (29.5%), so that overall ocular survival has been 73.5%. Local tumor control with external beam radiotherapy alone was obtained in 78.5% (11 out of 14) of eyes in Groups I-II, but in only 20% (4 out of 20) of eyes in Groups III-V. A total of 67 existing tumors were identified prior to treatment in the 34 treated eyes and local control with external beam radiation alone was obtained in 87% (46 out of 53) of tumors measuring 15 mm or less and in 50% (7 out of 14) of tumors measuring more than 15 mm. When analyzing patterns of failure in the 19 eyes that relapsed, a total of 28 failure sites were identified and consisted of progression of vitreous seeds in seven instances (25% of failure sites) recurrences from previously existing tumors in 10 instances (36% of failure sites) and development of new tumors in previously uninvolved retina in 11 instances (39% of failure sites). Conclusions: 1) We find that external beam radiation to a dose of 45 Gy in fractions of 1.5 to 2.0 Gy provides adequate tumor control

  6. Niewydolność serca - definicja, klasyfikacja, epidemiologia, objawy i leczenie = Heart failure - definition, classification, epidemiology, symptoms and treatment

    Directory of Open Access Journals (Sweden)

    Beata Kowalczyk

    2017-02-01

      Streszczenie   W ciągu ostatnich 50 lat pojawiło się wiele określeń niewydolności serca. Dokonał się również znaczący postęp w postrzeganiu i leczeniu tej choroby. Skuteczność leczenia i rehabilitacji przekłada się na redukcję klasy NYHA i poprawę frakcji wyrzutowej lewej komory serca. Istotnie poprawiło się rokowanie chorych z umiarkowaną i ciężką postacią niewydolności. Kluczem do wczesnego rozpoznania niewydolności serca są jej objawy przedmiotowe i podmiotowe. Niestety pomimo ogromnego rozwoju medycyny niewydolność serca jest nadal poważnym problemem klinicznym, społecznym i ekonomicznym. Liczba zachorowań stale rośnie. W kompleksowej opiece nad pacjentem z niewydolnością serca oprócz leczenia farmakologicznego znaczącą rolę odgrywa odpowiednie przygotowanie chorego do życia z niewydolnością serca. Celem artykułu jest podsumowanie zagadnień definicji, klasyfikacji, epidemiologii, objawów i leczenia niewydolności serca.   Słowa kluczowe: niewydolność serca, definicja, klasyfikacja, epidemiologia, leczenie.     Abstract   In the last 50 years there have been many definitions of heart failure. It has been made significant progress in the perception and treatment of the disease. The effectiveness of treatment and rehabilitation translates into a reduction in NYHA class and improve the ejection fraction of the left ventricle. Significantly improved the prognosis in patients with moderate or severe heart failure. The key to early diagnosis of heart failure are its signs and symptoms. Heart failure unfortunately continues despite the enormous development of medicine is serious clinical, social and economic problem. The number of cases continues to grow. In the comprehensive care of patients with heart failure in addition to pharmacological treatment plays an important role adequate preparation of the patient to live with heart failure. Objectives of this article is a summary of issues of definition

  7. Potential Impact of a Free Online HIV Treatment Response Prediction System for Reducing Virological Failures and Drug Costs after Antiretroviral Therapy Failure in a Resource-Limited Setting

    Directory of Open Access Journals (Sweden)

    Andrew D. Revell

    2013-01-01

    Full Text Available Objective. Antiretroviral drug selection in resource-limited settings is often dictated by strict protocols as part of a public health strategy. The objective of this retrospective study was to examine if the HIV-TRePS online treatment prediction tool could help reduce treatment failure and drug costs in such settings. Methods. The HIV-TRePS computational models were used to predict the probability of response to therapy for 206 cases of treatment change following failure in India. The models were used to identify alternative locally available 3-drug regimens, which were predicted to be effective. The costs of these regimens were compared to those actually used in the clinic. Results. The models predicted the responses to treatment of the cases with an accuracy of 0.64. The models identified alternative drug regimens that were predicted to result in improved virological response and lower costs than those used in the clinic in 85% of the cases. The average annual cost saving was $364 USD per year (41%. Conclusions. Computational models that do not require a genotype can predict and potentially avoid treatment failure and may reduce therapy costs. The use of such a system to guide therapeutic decision-making could confer health economic benefits in resource-limited settings.

  8. In-vivo fluorescence lifetime imaging for monitoring the efficacy of the cancer treatment

    Science.gov (United States)

    Ardeshirpour, Yasaman; Chernomordik, Victor; Hassan, Moinuddin; Zielinski, Rafal; Capala, Jacek; Gandjbakhche, Amir

    2015-01-01

    Purpose Advances in tumor biology created a foundation for targeted therapy aimed at inactivation of specific molecular mechanisms responsible for cell malignancy. In this paper, we used in-vivo fluorescence lifetime imaging with HER2 targeted fluorescent probes as an alternative imaging method to investigate the efficacy of targeted therapy with 17-DMAG (an HSP90 inhibitor) on tumors with high expression of HER2 receptors. Experimental Design HER2-specific Affibody, conjugated to Alexafluor 750, was injected into nude mice, bearing HER2-positive tumor xenograft. The fluorescence lifetime was measured before treatment and monitored after the probe injections at 12 hours after the last treatment dose, when the response to the 17-DMAG therapy was the most pronounced as well as a week after the last treatment when the tumors grew back almost to their pre-treatment size. Results Imaging results showed significant difference between the fluorescence lifetimes at the tumor and the contralateral site (~0.13ns) in the control group (before treatment) and 7 days after the last treatment when the tumors grew back to their pretreatment dimensions. However, at the time frame that the treatment had its maximum effect (12 hours after the last treatment) the difference between the fluorescence lifetime at the tumor and contralateral site decreased to 0.03ns. Conclusions The results showed a good correlation between fluorescence lifetime and the efficacy of the treatment. These findings show that in-vivo fluorescence lifetime imaging can be used as a promising molecular imaging tool for monitoring the treatment outcome in preclinical models and potentially in patients. PMID:24671949

  9. Evaluation of Brace Treatment for Infant Hip Dislocation in a Prospective Cohort: Defining the Success Rate and Variables Associated with Failure.

    Science.gov (United States)

    Upasani, Vidyadhar V; Bomar, James D; Matheney, Travis H; Sankar, Wudbhav N; Mulpuri, Kishore; Price, Charles T; Moseley, Colin F; Kelley, Simon P; Narayanan, Unni; Clarke, Nicholas M P; Wedge, John H; Castañeda, Pablo; Kasser, James R; Foster, Bruce K; Herrera-Soto, Jose A; Cundy, Peter J; Williams, Nicole; Mubarak, Scott J

    2016-07-20

    The use of a brace has been shown to be an effective treatment for hip dislocation in infants; however, previous studies of such treatment have been single-center or retrospective. The purpose of the current study was to evaluate the success rate for brace use in the treatment of infant hip dislocation in an international, multicenter, prospective cohort, and to identify the variables associated with brace failure. All dislocations were verified with use of ultrasound or radiography prior to the initiation of treatment, and patients were followed prospectively for a minimum of 18 months. Successful treatment was defined as the use of a brace that resulted in a clinically and radiographically reduced hip, without surgical intervention. The Mann-Whitney test, chi-square analysis, and Fisher exact test were used to identify risk factors for brace failure. A multivariate logistic regression model was used to determine the probability of brace failure according to the risk factors identified. Brace treatment was successful in 162 (79%) of the 204 dislocated hips in this series. Six variables were found to be significant risk factors for failure: developing femoral nerve palsy during brace treatment (p = 0.001), treatment with a static brace (p failure, whereas hips with 4 or 5 risk factors had a 100% probability of failure. These data provide valuable information for patient families and their providers regarding the important variables that influence successful brace treatment for dislocated hips in infants. Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

  10. 20 CFR 416.1326 - Suspension for failure to comply with treatment for drug addiction or alcoholism.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Suspension for failure to comply with treatment for drug addiction or alcoholism. 416.1326 Section 416.1326 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Suspensions and Terminations § 416.1326 Suspension for failure to comply...

  11. Treatment Failure and Mortality amongst Children with Severe Acute Malnutrition Presenting with Cough or Respiratory Difficulty and Radiological Pneumonia

    Science.gov (United States)

    Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Bardhan, Pradip Kumar; Faruque, Abu S. G.; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Hossain, Md Iqbal; Ahmed, Tahmeed

    2015-01-01

    Background Appropriate intervention is critical in reducing deaths among under-five, severe acutely malnourished (SAM) children with danger signs of severe pneumonia; however, there is paucity of data on outcome of World Health Organisation (WHO) recommended interventions of SAM children with severe pneumonia. We sought to evaluate outcome of the interventions in such children. Methods We prospectively enrolled SAM children aged 0–59 months, admitted to the Intensive Care Unit (ICU) or Acute Respiratory Infection (ARI) ward of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), between April 2011 and June 2012 with cough or respiratory difficulty and radiological pneumonia. All the enrolled children were treated with ampicillin and gentamicin, and micronutrients as recommended by the WHO. Comparison was made among pneumonic children with (n = 111) and without WHO defined danger signs of severe pneumonia (n = 296). The outcomes of interest were treatment failure (if a child required changing of antibiotics) and deaths during hospitalization. Further comparison was also made among those who developed treatment failure and who did not and among the survivors and deaths. Results SAM children with danger signs of severe pneumonia more often experienced treatment failure (58% vs. 20%; ppp<0.01). Conclusion and Significance The result suggests that SAM children with cough or respiratory difficulty and radiologic pneumonia who had WHO-defined danger signs of severe pneumonia more often had treatment failure and fatal outcome compared to those without the danger signs. In addition to danger signs of severe pneumonia, other common causes of both treatment failure and deaths were dehydration, hypocalcaemia, and bacteraemia on admission. The result underscores the importance for further research especially a randomized, controlled clinical trial to validate standard WHO therapy in SAM children with pneumonia especially with

  12. Treatment failure after uterine artery embolization: Prospective cohort study with multifactorial analysis of possible predictors of long-term outcome

    International Nuclear Information System (INIS)

    Scheurig-Muenkler, Christian; Koesters, Clemens; Grieser, Christian; Hamm, Bernd; Kroencke, Thomas J.

    2012-01-01

    Purpose: To evaluate the impact of baseline characteristics and residual leiomyoma perfusion after uterine artery embolization (UAE) on clinical long-term outcome. Materials and methods: One hundred fifteen patients underwent UAE. All patients were divided into three groups according to achieved infarction rate determined on contrast-enhanced magnetic resonance imaging within 48–72 h after UAE (I: 100%, n = 60; II: 90–99%, n = 32; and III: 0–89%, n = 23). Treatment failure and subsequent re-interventions (surgery, repeat UAE) were assessed for each group and compared using Cox regression analysis (CRA) with respect to the following baseline variables: age, uterine and dominant fibroid volume, number of fibroids, location of largest fibroid, and clinical symptoms. Results: Long-term follow-up was completed after a median of 7.2 years (range 5.1–9.6) with a response rate of 84%. CRA revealed that patients in group III had a 22.2-fold higher risk (p < 0.001) of treatment failure than patients in group I, whereas groups I and II did not differ significantly (p = 0.578). For patients with bleeding-related symptoms only, CRA showed a 5.1-fold higher risk (p = 0.025) of treatment failure than for patients with equally dominant bleeding- and bulk-related symptoms. A 40.5-fold higher likelihood (p < 0.001) of treatment failure was observed for patients in group III with bleeding-related symptoms only compared to those in group I with combined bleeding- and bulk-related symptoms. Conclusion: Incomplete fibroid infarction after UAE is strongly associated with the risk of experiencing treatment failure. Patients with bleeding-related complaints only face the highest likelihood of treatment failure if UAE results in less than 90% fibroid devascularization.

  13. Low-frequency blood pressure oscillations and inotrope treatment failure in premature infants.

    Science.gov (United States)

    Vesoulis, Zachary A; Hao, Jessica; McPherson, Christopher; El Ters, Nathalie M; Mathur, Amit M

    2017-07-01

    The underlying mechanism as to why some hypotensive preterm infants do not respond to inotropic medications remains unclear. For these infants, we hypothesize that impaired vasomotor function is a significant factor and is manifested through a decrease in low-frequency blood pressure variability across regulatory components of vascular tone. Infants born ≤28 wk estimated gestational age underwent prospective recording of mean arterial blood pressure for 72 h after birth. After error correction, root-mean-square spectral power was calculated for each valid 10-min data frame across each of four frequency bands ( B1 , 0.005-0.0095 Hz; B2 , 0.0095-0.02 Hz; B3 , 0.02-0.06 Hz; and B4 , 0.06-0.16) corresponding to different components of vasomotion control. Forty infants (twenty-nine normotensive control and eleven inotrope-exposed) were included with a mean ± SD estimated gestational age of 25.2 ± 1.6 wk and birth weight 790 ± 211 g. 9.7/11.8 Million (82%) data points were error-free and used for analysis. Spectral power across all frequency bands increased with time, although the magnitude was 20% less in the inotrope-exposed infants. A statistically significant increase in spectral power in response to inotrope initiation was noted across all frequency bands. Infants with robust blood pressure response to inotropes had a greater increase compared with those who had limited or no blood pressure response. In this study, hypotensive infants who require inotropes have decreased low-frequency variability at baseline compared with normotensive infants, which increases after inotrope initiation. Low-frequency spectral power does not change for those with inotrope treatment failure, suggesting dysfunctional regulation of vascular tone as a potential mechanism of treatment failure. NEW & NOTEWORTHY In this study, we examine patterns of low-frequency oscillations in blood pressure variability across regulatory components of vascular tone in normotensive and

  14. Defining human mesenchymal stem cell efficacy in vivo

    Directory of Open Access Journals (Sweden)

    Lennon Donald P

    2010-10-01

    Full Text Available Abstract Allogeneic human mesenchymal stem cells (hMSCs can suppress graft versus host disease (GvHD and have profound anti-inflammatory and regenerative capacity in stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of disease. There is significant clinical hMSC variability in efficacy and the ultimate response in vivo. The challenge in hMSC based therapy is defining the efficacy of hMSC in vivo. Models which may provide insight into hMSC bioactivity in vivo would provide a means to distinguish hMSCs for clinical utility. hMSC function has been described as both regenerative and trophic through the production of bioactive factors. The regenerative component involves the multi-potentiality of hMSC progenitor differentiation. The secreted factors generated by the hMSCs are milieu and injury specific providing unique niches for responses in vivo. These bioactive factors are anti-scarring, angiogenic, anti-apoptotic as well as regenerative. Further, from an immunological standpoint, hMSC's can avoid host immune response, providing xenographic applications. To study the in vivo immuno-regulatory effectiveness of hMSCs, we used the ovalbumin challenge model of acute asthma. This is a quick 3 week in vivo pulmonary inflammation model with readily accessible ways of measuring effectiveness of hMSCs. Our data show that there is a direct correlation between the traditional ceramic cube score to hMSCs attenuation of cellular recruitment due to ovalbumin challenge. The results from these studies verify the in vivo immuno-modulator effectiveness of hMSCs and support the potential use of the ovalbumin model as an in vivo model of hMSC potency and efficacy. Our data also support future directions toward exploring hMSCs as an alternative therapeutic for the treatment of airway inflammation associated with asthma.

  15. The multi-class binomial failure rate model for the treatment of common-cause failures

    International Nuclear Information System (INIS)

    Hauptmanns, U.

    1995-01-01

    The impact of common cause failures (CCF) on PSA results for NPPs is in sharp contrast with the limited quality which can be achieved in their assessment. This is due to the dearth of observations and cannot be remedied in the short run. Therefore the methods employed for calculating failure rates should be devised such as to make the best use of the few available observations on CCF. The Multi-Class Binomial Failure Rate (MCBFR) Model achieves this by assigning observed failures to different classes according to their technical characteristics and applying the BFR formalism to each of these. The results are hence determined by a superposition of BFR type expressions for each class, each of them with its own coupling factor. The model thus obtained flexibly reproduces the dependence of CCF rates on failure multiplicity insinuated by the observed failure multiplicities. This is demonstrated by evaluating CCFs observed for combined impulse pilot valves in German NPPs. (orig.) [de

  16. In vivo fluorescence lifetime imaging for monitoring the efficacy of the cancer treatment.

    Science.gov (United States)

    Ardeshirpour, Yasaman; Chernomordik, Victor; Hassan, Moinuddin; Zielinski, Rafal; Capala, Jacek; Gandjbakhche, Amir

    2014-07-01

    Advances in tumor biology created a foundation for targeted therapy aimed at inactivation of specific molecular mechanisms responsible for cell malignancy. In this paper, we used in vivo fluorescence lifetime imaging with HER2-targeted fluorescent probes as an alternative imaging method to investigate the efficacy of targeted therapy with 17-DMAG (an HSP90 inhibitor) on tumors with high expression of HER2 receptors. HER2-specific Affibody, conjugated to Alexafluor 750, was injected into nude mice bearing HER2-positive tumor xenograft. The fluorescence lifetime was measured before treatment and monitored after the probe injections at 12 hours after the last treatment dose, when the response to the 17-DMAG therapy was the most pronounced as well as a week after the last treatment when the tumors grew back almost to their pretreatment size. Imaging results showed significant difference between the fluorescence lifetimes at the tumor and the contralateral site (∼0.13 ns) in the control group (before treatment) and 7 days after the last treatment when the tumors grew back to their pretreatment dimensions. However, at the time frame that the treatment had its maximum effect (12 hours after the last treatment), the difference between the fluorescence lifetime at the tumor and contralateral site decreased to 0.03 ns. The results showed a good correlation between fluorescence lifetime and the efficacy of the treatment. These findings show that in vivo fluorescence lifetime imaging can be used as a promising molecular imaging tool for monitoring the treatment outcome in preclinical models and potentially in patients. ©2014 American Association for Cancer Research.

  17. Metabolic determinants of electrical failure in ex-vivo canine model of cardiac arrest: evidence for the protective role of inorganic pyrophosphate.

    Directory of Open Access Journals (Sweden)

    Junko Shibayama

    Full Text Available Deterioration of ventricular fibrillation (VF into asystole or severe bradycardia (electrical failure heralds a fatal outcome of cardiac arrest. The role of metabolism in the timing of electrical failure remains unknown.To determine metabolic factors of early electrical failure in an ex-vivo canine model of cardiac arrest (VF+global ischemia.Metabolomic screening was performed in left ventricular biopsies collected before and after 0.3, 2, 5, 10 and 20 min of VF and global ischemia. Electrical activity was monitored via plunge needle electrodes and pseudo-ECG. Four out of nine hearts exhibited electrical failure at 10.1±0.9 min (early-asys, while 5/9 hearts maintained VF for at least 19.7 min (late-asys. As compared to late-asys, early-asys hearts had more ADP, less phosphocreatine, and higher levels of lactate at some time points during VF/ischemia (all comparisons p<0.05. Pre-ischemic samples from late-asys hearts contained ∼25 times more inorganic pyrophosphate (PPi than early-asys hearts. A mechanistic role of PPi in cardioprotection was then tested by monitoring mitochondrial membrane potential (ΔΨ during 20 min of simulated-demand ischemia using potentiometric probe TMRM in rabbit adult ventricular myocytes incubated with PPi versus control group. Untreated myocytes experienced significant loss of ΔΨ while in the PPi-treated myocytes ΔΨ was relatively maintained throughout 20 min of simulated-demand ischemia as compared to control (p<0.05.High tissue level of PPi may prevent ΔΨm loss and electrical failure at the early phase of ischemic stress. The link between the two protective effects may involve decreased rates of mitochondrial ATP hydrolysis and lactate accumulation.

  18. Ovarian failure and cancer treatment: Incidence and interventions for premenopausal women

    International Nuclear Information System (INIS)

    Feldman, J.E.

    1989-01-01

    Ovarian failure may be a long-term consequence of cancer treatment for premenopausal women. Caused by several treatments, including radiation therapy and the alkylating agents, it produces signs and symptoms associated with menopause: hot flashes, amenorrhea, dyspareunia, loss of libido, and irritability. Critical factors that determine ovarian functioning after treatment for cancer are the patient's age at the time of therapy, the amount of radiation that the ovaries received, and the dose of the antineoplastic agent(s). Medical interventions, such as hormonal therapy and surgical repositioning of the ovaries, may maintain ovarian function for some women. Nursing intervention includes assessment, education, and counseling. Counseling focuses on how the prematurely menopausal patient feels about herself as indicated by self-esteem, body image, and sexuality

  19. Ovarian failure and cancer treatment: Incidence and interventions for premenopausal women

    Energy Technology Data Exchange (ETDEWEB)

    Feldman, J.E.

    1989-09-01

    Ovarian failure may be a long-term consequence of cancer treatment for premenopausal women. Caused by several treatments, including radiation therapy and the alkylating agents, it produces signs and symptoms associated with menopause: hot flashes, amenorrhea, dyspareunia, loss of libido, and irritability. Critical factors that determine ovarian functioning after treatment for cancer are the patient's age at the time of therapy, the amount of radiation that the ovaries received, and the dose of the antineoplastic agent(s). Medical interventions, such as hormonal therapy and surgical repositioning of the ovaries, may maintain ovarian function for some women. Nursing intervention includes assessment, education, and counseling. Counseling focuses on how the prematurely menopausal patient feels about herself as indicated by self-esteem, body image, and sexuality.

  20. Smoking increases the likelihood of Helicobacter pylori treatment failure.

    Science.gov (United States)

    Itskoviz, David; Boltin, Doron; Leibovitzh, Haim; Tsadok Perets, Tsachi; Comaneshter, Doron; Cohen, Arnon; Niv, Yaron; Levi, Zohar

    2017-07-01

    Data regarding the impact of smoking on the success of Helicobacter pylori (H. pylori) eradication are conflicting, partially due to the fact that sociodemographic status is associated with both smoking and H. pylori treatment success. We aimed to assess the effect of smoking on H. pylori eradication rates after controlling for sociodemographic confounders. Included were subjects aged 15 years or older, with a first time positive C 13 -urea breath test (C 13 -UBT) between 2007 to 2014, who underwent a second C 13 -UBT after receiving clarithromycin-based triple therapy. Data regarding age, gender, socioeconomic status (SES), smoking (current smokers or "never smoked"), and drug use were extracted from the Clalit health maintenance organization database. Out of 120,914 subjects with a positive first time C 13 -UBT, 50,836 (42.0%) underwent a second C 13 -UBT test. After excluding former smokers, 48,130 remained who were eligible for analysis. The mean age was 44.3±18.2years, 69.2% were females, 87.8% were Jewish and 12.2% Arabs, 25.5% were current smokers. The overall eradication failure rates were 33.3%: 34.8% in current smokers and 32.8% in subjects who never smoked. In a multivariate analysis, eradication failure was positively associated with current smoking (Odds Ratio {OR} 1.15, 95% CI 1.10-1.20, psmoking was found to significantly increase the likelihood of unsuccessful first-line treatment for H. pylori infection. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  1. Treatment actions and treatment failure: case studies in the response to severe childhood febrile illness in Mali

    Directory of Open Access Journals (Sweden)

    Ellis Amy A

    2012-11-01

    Full Text Available Abstract Background Appropriate home management of illness is vital to efforts to control malaria. The strategy of home management relies on caregivers to recognize malaria symptoms, assess severity and promptly seek appropriate care at a health facility if necessary. This paper examines the management of severe febrile illness (presumed malaria among children under the age of five in rural Koulikoro Region, Mali. Methods This research examines in-depth case studies of twenty-five households in which a child recently experienced a severe febrile illness, as well as key informant interviews and focus group discussions with community members. These techniques were used to explore the sequence of treatment steps taken during a severe illness episode and the context in which decisions were made pertaining to pursing treatments and sources of care, while incorporating the perspective and input of the mother as well as the larger household. Results Eighty-one participants were recruited in 25 households meeting inclusion criteria. Children's illness episodes involved multiple treatment steps, with an average of 4.4 treatment steps per episode (range: 2–10. For 76% of children, treatment began in the home, but 80% were treated outside the home as a second recourse. Most families used both traditional and modern treatments, administered either inside the home by family members, or by traditional or modern healers. Participants’ stated preference was for modern care, despite high rates of reported treatment failure (52%, n=12, however, traditional treatments were also often deemed appropriate and effective. The most commonly cited barrier to seeking care at health facilities was cost, especially during the rainy season. Financial constraints often led families to use traditional treatments. Conclusions Households have few options available to them in moments of overlapping health and economic crises. Public health research and policy should focus on

  2. Clinical significance of determination of changes of serum APN, BNP and ANF levels after treatment in patients with heart failure

    International Nuclear Information System (INIS)

    Ge Hengsong; Hu Min; Gao Xinchun

    2011-01-01

    Objective: To explore the significance of changes on serum APN, BNP and ANF levels after treatment in patients with heart failure. Methods: Serum BNP, ANF(with RIA) serum APN (with ELISA) levels were determined in 30 patients with heart failure both before and after treatment as well as in 35 normal controls. Results: Before treatment, serum APN level was significantly lower than those in controls (P<0.01), but serum BNP, ANF levels were apparently higher (P<0.01). After 1 month of treatment, the levels dropped markedly, but still remained obviously higher (P<0.05). Conclusion: Serum APN, BNP and ANF levels were closely related to the process of heart failure and were of clinical value of monitoring therapeutic effect and prognosis. (authors)

  3. LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure.

    Science.gov (United States)

    Andersen, Mathilde Borring; Simonsen, Ulf; Wehland, Markus; Pietsch, Jessica; Grimm, Daniela

    2016-01-01

    The aim of this MiniReview was to introduce the newly invented dual-acting drug valsartan/sacubitril (LCZ696), which combines an angiotensin receptor blocker (valsartan) with sacubitril, a specific inhibitor of the neutral endopeptidase (NEP) that degrades vasoactive peptides, including natriuretic peptides ANP and BNP, but also glucagon, enkephalins and bradykinin, among others. The MiniReview presents the data of four available trials NCT01193101, NCT00549770, NCT00887588 and NCT01035255 and provides the current knowledge about LCZ696 effects in patients with hypertension and heart failure. Presently, patients suffering from hypertension and heart failure are treated with ACE inhibitors or angiotensin receptor antagonists often in combination with other drugs. These current medications lead to a reduction in blood pressure in hypertensive patients and a decreased mortality and morbidity in patients with heart failure with reduced ejection fraction, but not in patients with heart failure with preserved ejection fraction. LCZ696 had been tested to utilize the beneficial properties of natriuretic peptides in combination with angiotensin receptor antagonism. It induces even greater blood pressure reductions and decreased mortality and morbidity in patients with heart failure with reduced ejection fraction, while patients with heart failure with preserved ejection fraction show lowered blood pressure and decreased NT-pro-BNP levels. Although long-term studies remain to be performed, these initial data suggest that there is a potential clinical benefit of LCZ696 in the treatment of hypertension and heart failure. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  4. Advantages, Disadvantages, and Trend of Integrative Medicine in the Treatment of Heart Failure.

    Science.gov (United States)

    Zhang, PeiYing

    2015-06-01

    Integrative medicine therapy using traditional Chinese medicine (TCM) combined with western medicine has shown some advantages in treating heart failure (HF), such as holistic concept; multi-target treatment; dialectical logic; personalized therapy; formulae compatibility; and reduction of side effects of western medicine. However, problems still exist in TCM treatment of HF, including non-uniformed categorization of TCM, lack of standardized syndrome differentiation and lack of an evidence base. The future of treatment of HF seems to be focused on reversing ventricular remodeling, improving cardiac rehabilitation, and accelerating experimental research and drug discovery in TCM.

  5. Factors associated with syphilis treatment failure and reinfection: a longitudinal cohort study in Shenzhen, China.

    Science.gov (United States)

    Luo, Zhenzhou; Zhu, Lin; Ding, Yi; Yuan, Jun; Li, Wu; Wu, Qiuhong; Tian, Lishan; Zhang, Li; Zhou, Guomao; Zhang, Tao; Ma, Jianping; Chen, Zhongwei; Yang, Tubao; Feng, Tiejian; Zhang, Min

    2017-09-13

    The treatment failure and reinfection rates among syphilis patients are high, and relevant studies in China are limited. The aim of this study was to detect the rates of treatment failure and reinfection after syphilis treatment and to explore the potential associated factors. We conducted a longitudinal cohort study in a sexually transmitted disease clinic, the Department of Dermatology and Venereology in Nanshan Center for Chronic Disease Control. Serological testing was performed at baseline and throughout the 2-year follow-up for syphilis patients. To identify potential predictors of treatment outcomes, multivariate logistics analyses were utilized to compare the demographic and clinical characteristics of patients with serological failure/reinfection to those with serological cure/serofast. From June 2011 to June 2016, a total of 1133 patients were screened for syphilis. Among the 770 patients who completed the 2-year follow-up, 510 first-diagnosed patients were included in the final analysis. Multivariate logistics analysis revealed the stage of syphilis (secondary syphilis VS. primary syphilis: adjusted odds ratio, 3.50; 95% confidence interval, 1.11-15.47; p = 0.04), HIV status (positive VS. negative: adjusted odds ratio, 3.06; 95% confidence interval, 1.15-8.04; p = 0.02) and frequency of condom use (always use VS. never use: adjusted odds ratio, 0.28; 95% confidence interval 0.08-0.75; p = 0.02) were significantly associated with the serological outcome. The clinical implications of our findings suggest that it is very important to perform regular clinical and serologic evaluations after treatment. Health counseling and safety education on sex activity should be intensified among HIV-infected patients and secondary syphilis patients after treatment.

  6. Treatment failure of nelfinavir-containing triple therapy can largely be explained by low nelfinavir plasma concentrations

    NARCIS (Netherlands)

    Burger, David M.; Hugen, Patricia W. H.; Aarnoutse, Rob E.; Hoetelmans, Richard M. W.; Jambroes, Marielle; Nieuwkerk, Pythia T.; Schreij, Gerrit; Schneider, Margriet M. E.; van der Ende, Marchina E.; Lange, Joep M. A.

    2003-01-01

    The relationship between plasma concentrations of nelfinavir and virologic treatment failure was investigated to determine the minimum effective concentration of nelfinavir. Plasma samples were prospectively collected from treatment-naive patients who began taking nelfinavir, 1,250 mg BID + two

  7. Successful treatment of severe sinusoidal obstruction syndrome despite multiple organ failure with defibrotide after allogeneic stem cell transplantation: a case report.

    Science.gov (United States)

    Behre, Gerhard; Theurich, Sebastian; Christopeit, Maximilian; Weber, Thomas

    2009-03-10

    We report a case of sinusoidal obstruction syndrome, a typical and life-threatening complication after allogeneic stem-cell transplantation, successfully treated with defibrotide despite massive multiple organ failure. A 64-year-old Caucasian woman underwent allogeneic peripheral blood stem-cell transplantation from her human leukocyte antigen-identical sister against aggressive lymphoplasmocytoid immunocytoma. Seven days later, the patient developed severe sinusoidal obstruction syndrome according to the modified Seattle criteria. We initiated treatment with defibrotide. Despite early treatment, multiple organ failure with kidney failure requiring dialysis and ventilator-dependent lung failure aggravated the clinical course. Furthermore, central nervous dysfunction occurred as well as transfusion refractory thrombocytopenia. As highlighted in our report, defibrotide is the most promising drug in the treatment of the formerly, almost lethal, severe sinusoidal obstruction syndrome to date. This is demonstrated very clearly in our patient. She improved completely, even after renal, cerebral and respiratory failure.

  8. In vivo preclinical evaluation of the accuracy of toroidal-shaped HIFU treatments using a tumor-mimic model

    International Nuclear Information System (INIS)

    N'Djin, W A; Melodelima, D; Parmentier, H; Chapelon, J Y; Rivoire, M

    2010-01-01

    The pig is an ideal animal model for preclinical evaluation of HIFU treatments, especially in the liver. However, there is no liver tumor model available for pigs. In this work, we propose to study an in vivo tumor-mimic model as a tool for evaluating if a sonographycally guided HIFU treatment, delivered by a toroidal-shaped device dedicated for the treatment of liver metastases, is correctly located in the liver. One centimeter tumor-mimics were created in liver tissues. These tumor-mimics were detectable on ultrasound imaging and on gross pathology. Two studies were carried out. First, an in vivo study of tolerance at mid-term (30 days, 10 pigs) revealed that tumor-mimics are suitable for studying HIFU treatments at a preclinical stage, since local and biological tolerances were excellent. The dimensions of the tumor-mimics were reproducible (diameter at day 0: 9.7 ± 2.0 mm) and were the same as a function of time (p = 0.64). A second in vivo study was carried out in ten pigs. Tumor mimics were used as targets in liver tissues in order to determine if the HIFU treatment is correctly located in the liver. A procedure of extensive HIFU ablation using multiple HIFU lesions juxtaposed manually was then tested on eight tumor-mimics. In 88% of the cases (seven out of eight), tumor-mimics were treated with negative margins (≥1 mm) in all directions. On average, negative margins measured 10.0 ± 6.7 mm. These tumor-mimics constitute an excellent reference for studying in vivo the accuracy of HIFU therapy in the liver.

  9. Retrospective 25-year follow-up of treatment outcomes in Angle Class III patients : Success versus failure.

    Science.gov (United States)

    Wendl, Brigitte; Kamenica, A; Droschl, H; Jakse, N; Weiland, F; Wendl, T; Wendl, M

    2017-03-01

    Despite recommendations for early treatment of hereditary Angle Class III syndrome, late pubertal growth may cause a relapse requiring surgical intervention. This study was performed to identify predictors of successful Class III treatment. Thirty-eight Class III patients treated with a chincup were retrospectively analyzed. Data were collected from the data archive, cephalograms, and casts, including pretreatment (T0) and posttreatment (T1) data, as well as long-term follow-up data collected approximately 25 years after treatment (T2). Each patient was assigned to a success or a failure group. Data were analyzed based on time (T0, T1, T2), deviations from normal (Class I), and prognathism types (true mandibular prognathism, maxillary retrognathism, combined pro- and retrognathism). Compared to Class I normal values, the data obtained in both groups yielded 11 significant parameters. The success group showed values closer to normal at all times (T0, T1, T2) and vertical parameters decreased from T0 to T2. The failure group showed higher values for vertical and horizontal mandibular growth, as well as dentally more protrusion of the lower anterior teeth and more negative overjet at all times. In adittion, total gonial and upper gonial angle were higher at T0 and T1. A prognostic score-yet to be evaluated in clinical practice-was developed from the results. The failure group showed greater amounts of horizontal development during the years between T1 and T2. Treatment of true mandibular prognathism achieved better outcomes in female patients. Cases of maxillary retrognathism were treated very successfully without gender difference. Failure was clearly more prevalent, again without gender difference, among the patients with combined mandibular prognathism and maxillary retrognathism. Crossbite situations were observed in 44% of cases at T0. Even though this finding had been resolved by T1, it relapsed in 16% of the cases by T2. The failure rate increased in cases of

  10. Drug resistance pattern of M. tuberculosis in category II treatment failure pulmonary tuberculosis patients

    Directory of Open Access Journals (Sweden)

    Fahmida Rahman

    2013-01-01

    Full Text Available This study was designed to determine the extent of drug resistance of M. tuberculosis (MTB isolated from category II treatment failure pulmonary tuberculosis (PTB patients. A total of 100 Ziehl-Neelsen (Z-N smear positive category II failure PTB patients were included in this study. Sputum culture was done in Lowenstein-Jensen (L-J media. Conventional proportion method on Lowenstein-Jensen (L-J media was used to determine the drug susceptibility of M. tuberculosis to isoniazid (INH, rifampicin (RMP, ofloxacin (OFX and kanamycin (KA. Out of 100 sputum samples, a total of 87 samples were positive by culture. Drug susceptibility test (DST revealed that 82 (94.25% isolates were resistant to one or more anti -TB drugs. Resistance to isoniazide (INH, rifampicin (RMP, ofloxacin (OFX and kanamycin (KA was 94.25%, 82.75%, 29.90% and 3.45% respectively. Among these isolates, 79.31% and 3.45% isolates were multi-drug resistant (MDR and extended drug resistant (XDR M. tuberculosis respectively. High rate of anti-tubercular drug resistance was observed among the category II treatment failure TB patients. Ibrahim Med. Coll. J. 2013; 7(1: 9-11

  11. Empagliflozin Prevents Worsening of Cardiac Function in an Experimental Model of Pressure Overload-Induced Heart Failure

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    Nikole J. Byrne, BSc

    2017-08-01

    Full Text Available This study sought to determine whether the sodium/glucose cotransporter 2 (SGLT2 inhibitor empagliflozin improved heart failure (HF outcomes in nondiabetic mice. The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients trial demonstrated that empagliflozin markedly prevented HF and cardiovascular death in subjects with diabetes. However, despite ongoing clinical trials in HF patients without type 2 diabetes, there are no objective and translational data to support an effect of SGLT2 inhibitors on cardiac structure and function, particularly in the absence of diabetes and in the setting of established HF. Male C57Bl/6 mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Following surgery, mice that progressed to HF received either vehicle or empagliflozin for 2 weeks. Cardiac function was then assessed in vivo using echocardiography and ex vivo using isolated working hearts. Although vehicle-treated HF mice experienced a progressive worsening of cardiac function over the 2-week treatment period, this decline was blunted in empagliflozin-treated HF mice. Treatment allocation to empagliflozin resulted in an improvement in cardiac systolic function, with no significant changes in cardiac remodeling or diastolic dysfunction. Moreover, isolated hearts from HF mice treated with empagliflozin displayed significantly improved ex vivo cardiac function compared to those in vehicle-treated controls. Empagliflozin treatment of nondiabetic mice with established HF blunts the decline in cardiac function both in vivo and ex vivo, independent of diabetes. These data provide important basic and translational clues to support the evaluation of SGLT2 inhibitors as a treatment strategy in a broad range of patients with established HF.

  12. Use of Diuretics in the Treatment of Heart Failure in Older Adults.

    Science.gov (United States)

    Sica, Domenic A; Gehr, Todd W B; Frishman, William H

    2017-07-01

    Diuretics are the most commonly prescribed class of drugs in patients with heart failure, and in the short term they remain the most effective treatment for relief from fluid congestion. This article reviews the mode of action of the various diuretic classes and the physiologic adaptations that follow and sets up the basis for their use in the treatment of volume-retaining states, particularly as applies to the elderly. In addition, the article reviews the common side effects related to diuretics. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Treatment of chronic heart failure with aldosterone-blocking agents

    NARCIS (Netherlands)

    van Veldhuisen, Dirk J.; Swedberg, Karl

    Three large randomized trials in advanced heart failure (RALES), in heart failure after myocardial infarction (EPHESUS), and most recently mild heart failure (EMPHASIS-HF) have firmly established the place of aldosterone-blocking agents in patients with heart failure. In this paper we will shortly

  14. Patterns of failure following treatment for medulloblastoma: is it necessary to treat the entire posterior fossa?

    International Nuclear Information System (INIS)

    Fukunaga-Johnson, Nina; Lee, Jason H.; Robertson, Patricia; Sandler, Howard M.; McNeil, Elizabeth; Goldwein, Joel W.

    1997-01-01

    Purpose: Craniospinal radiation (CSRT) followed by a boost to the entire posterior fossa (PF) is standard post-operative therapy for patients with medulloblastoma. A large proportion of recurrences after treatment are local with approximately 50-70% of recurrences occurring in the PF. It is unclear, however, whether these failures are occurring in the original tumor bed, or outside the tumor bed but still within the PF. With improved diagnostic imaging, better definition of tumor volumes, and the use of 3D conformal therapy, we may be able to restrict the boost volume to the tumor bed plus a margin without compromising local control. This retrospective study analyzes the patterns of failure within the PF of a series of patients treated with radiation therapy (RT). Methods: From (7(86)) through (2(96)), 27 of 114 (24%) patients > 18 mo and < 18 yr with medulloblastoma, who were treated at the University of Michigan and Children's Hospital of Philadelphia, with RT following surgical resection were found to have a recurrence. RT consisted of CSRT followed by a boost to the entire posterior fossa. Patient's preoperative MRI and/or CT studies were used to compare the original tumor volume with the specific region of local relapse. Failure was defined as MRI or CT evidence of recurrence or positive cerebrospinal fluid cytology. Relapse was scored as local, if it was within the original tumor bed and regional, if it was outside of the tumor bed but still within the PF. Results: The median age of the patients was 8.6 years. Three patients were < 3 years old. (21(27)) had disease localized to the PF. (19(21)) patients received chemotherapy during their treatment regimen; 6 patients did not have information on systemic treatment. The median dose of RT to the craniospinal axis was 32.5 Gy and to the PF was 55.2 Gy. The median time to recurrence was 19.5 months. Local failure within the tumor bed as any component of first failure occurred in 52% ((14(27))) of all failures but

  15. Successful treatment of severe sinusoidal obstruction syndrome despite multiple organ failure with defibrotide after allogeneic stem cell transplantation: a case report

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    Behre Gerhard

    2009-03-01

    Full Text Available Abstract Introduction We report a case of sinusoidal obstruction syndrome, a typical and life-threatening complication after allogeneic stem-cell transplantation, successfully treated with defibrotide despite massive multiple organ failure. Case presentation A 64-year-old Caucasian woman underwent allogeneic peripheral blood stem-cell transplantation from her human leukocyte antigen-identical sister against aggressive lymphoplasmocytoid immunocytoma. Seven days later, the patient developed severe sinusoidal obstruction syndrome according to the modified Seattle criteria. We initiated treatment with defibrotide. Despite early treatment, multiple organ failure with kidney failure requiring dialysis and ventilator-dependent lung failure aggravated the clinical course. Furthermore, central nervous dysfunction occurred as well as transfusion refractory thrombocytopenia. Conclusion As highlighted in our report, defibrotide is the most promising drug in the treatment of the formerly, almost lethal, severe sinusoidal obstruction syndrome to date. This is demonstrated very clearly in our patient. She improved completely, even after renal, cerebral and respiratory failure.

  16. Efficacy of tegafur-uracil in advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy.

    Science.gov (United States)

    Maolake, Aerken; Izumi, Kouji; Takahashi, Rie; Itai, Shingo; Machioka, Kazuaki; Yaegashi, Hiroshi; Nohara, Takahiro; Kitagawa, Yasuhide; Kadono, Yoshifumi; Konaka, Hiroyuki; Mizokami, Atsushi; Namiki, Mikio

    2015-03-01

    Platinum-based chemotherapy is the first-line treatment for advanced urinary tract urothelial cancers. However, the optimal second-line treatment is unclear. Although tegafur-uracil is sometimes used for advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy, there is little evidence regarding its use as a second-line treatment. Advanced urothelial cancer patients previously treated with platinum-based chemotherapy were retrospectively analyzed. Overall survival (OS) was compared between patients with and without tegafur-uracil treatment. Thirty-one patients (27 and 4 patients with and without tegafur-uracil treatment, respectively) were analyzed. OS from the last day of the final chemotherapy course was better in patients with tegafur-uracil treatment than in those without (p<0.001, 358 and 66.5 days of the median survival time, respectively). Tegafur-uracil may be a candidate for the secondary treatment of advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Fibronectin and Kupffer cell function in fulminant hepatic failure

    International Nuclear Information System (INIS)

    Imawari, M.; Hughes, R.D.; Gove, C.D.; Williams, R.

    1985-01-01

    The relationship between plasma fibronectin, in vitro plasma opsonic activity, which measures the biological activity of fibronectin, and in vivo Kupffer cell function, as assessed by the systemic clearance of microaggregated [ 125 I]albumin, were determined simultaneously in 15 patients with fulminant hepatic failure and 12 normal subjects. Both the plasma fibronectin and plasma opsonic activity were significantly reduced in patients with fulminant hepatic failure, while the systemic clearance of microaggregated albumin was decreased. There was a significant correlation between plasma fibronectin and the plasma opsonic activity on admission, but no correlation could be detected between either parameter and the clearance of microaggregated albumin. A gelatin-derived plasma expander was shown to block the plasma opsonic activity both in vitro and in vivo. The low plasma fibronectin and decreased clearance of microaggregated albumin in fulminant hepatic failure reflect different aspects of the overall impairment of Kupffer cell function

  18. Patterns of Failure and Treatment-Related Toxicity in Advanced Cervical Cancer Patients Treated Using Extended Field Radiotherapy With Curative Intent

    International Nuclear Information System (INIS)

    Rajasooriyar, Chrishanthi; Van Dyk, Sylvia; Bernshaw, David; Kondalsamy-Chennakesavan, Srinivas; Barkati, Maroie; Narayan, Kailash

    2011-01-01

    Purpose: The purpose of this study was to evaluate the patterns of failure and overall survival (OS) and disease-free survival (DFS) rates in cervical cancer patients who had metastatic disease in common iliac or para-aortic lymph nodes and were treated with curative intent, using extended field radiotherapy (EFRT). Methods and Materials: This was a retrospective study involving 39 patients treated from January 1996 to June 2007, using EFRT with concurrent chemotherapy and intracavitary brachytherapy. EFRT consisted of 45 Gy in 1.8-Gy fractions. Radiation to involved nodes was boosted to a total dose of 50.4 to 54 Gy. Primary tumor radiation was boosted to a dose of 80 Gy using brachytherapy. Results: Overall, 30 patients (77%) have relapsed. The 5-year OS rate was 26% (95% confidence interval [CI], 11-44). The 5-year DFS rate was 19.4% (95% CI, 8-35). Only 3 patients (7.5%) experienced treatment failure exclusively within the treatment field, and 2 patients underwent salvage treatment. Grade 3 to 4 acute bone marrow and gastrointestinal toxicities were observed in 10 (26%) and 7 (18%) patients, respectively. Conclusions: Concurrent chemotherapy and EFRT treatment was well tolerated. Most patients showed failure at multiple sites and outside the treatment field. Only 3/39 patients had failures exclusively within the treatment field, and 2 underwent salvage treatment.

  19. Treatment Failure and Mortality amongst Children with Severe Acute Malnutrition Presenting with Cough or Respiratory Difficulty and Radiological Pneumonia.

    Directory of Open Access Journals (Sweden)

    Mohammod Jobayer Chisti

    Full Text Available Appropriate intervention is critical in reducing deaths among under-five, severe acutely malnourished (SAM children with danger signs of severe pneumonia; however, there is paucity of data on outcome of World Health Organisation (WHO recommended interventions of SAM children with severe pneumonia. We sought to evaluate outcome of the interventions in such children.We prospectively enrolled SAM children aged 0-59 months, admitted to the Intensive Care Unit (ICU or Acute Respiratory Infection (ARI ward of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b, between April 2011 and June 2012 with cough or respiratory difficulty and radiological pneumonia. All the enrolled children were treated with ampicillin and gentamicin, and micronutrients as recommended by the WHO. Comparison was made among pneumonic children with (n = 111 and without WHO defined danger signs of severe pneumonia (n = 296. The outcomes of interest were treatment failure (if a child required changing of antibiotics and deaths during hospitalization. Further comparison was also made among those who developed treatment failure and who did not and among the survivors and deaths.SAM children with danger signs of severe pneumonia more often experienced treatment failure (58% vs. 20%; p<0.001 and fatal outcome (21% vs. 4%; p<0.001 compared to those without danger signs. Only 6/111 (5.4% SAM children with danger signs of severe pneumonia and 12/296 (4.0% without danger signs had bacterial isolates from blood. In log-linear binomial regression analysis, after adjusting for potential confounders, danger signs of severe pneumonia, dehydration, hypocalcaemia, and bacteraemia were independently associated both with treatment failure and deaths in SAM children presenting with cough or respiratory difficulty and radiological pneumonia (p<0.01.The result suggests that SAM children with cough or respiratory difficulty and radiologic pneumonia who

  20. Digoxin affects potassium homeostasis during exercise in patients with heart failure.

    Science.gov (United States)

    Schmidt, T A; Bundgaard, H; Olesen, H L; Secher, N H; Kjeldsen, K

    1995-04-01

    The aim was to evaluate whether digitalisation of heart failure patients affects extrarenal potassium handling during and following exercise, and to assess digoxin receptor occupancy in human skeletal muscle in vivo. In a paired study of before versus after digitalisation, 10 patients with congestive heart failure underwent identical exercise sessions consisting of three bouts of increasing work rates, 41-93 W, on a cycle ergometer. The final bouts were followed by exercise to exhaustion. The femoral vessels and brachial artery were catheterised. Arterial blood pressure, heart rate, leg blood flow, cardiac output, plasma potassium, haemoglobin, pH, and skeletal muscle receptor occupancy with digoxin in biopsies were determined. Occupancy of skeletal muscle Na/K-ATPase with digoxin was 9% (P digitalisation femoral venous plasma potassium increased by 0.2-0.3 mmol.litre-1 (P digitalisation the femoral venoarterial difference in plasma potassium increased by 50-100% (P digitalisation on plasma potassium were not the outcome of changes in haemodynamics, because cardiac output and leg blood flow increased by up to 13% and 19% (P < 0.05), nor was it the outcome of changes in haemoconcentration or pH. Extrarenal potassium handling is altered as a result of digoxin treatment. This is likely to reflect a reduced capacity of skeletal muscle Na/K-ATPase for active potassium uptake because of inhibition by digoxin, adding to the reduction of skeletal muscle Na/K-ATPase concentration induced by heart failure per se. In heart failure patients, improved haemodynamics induced by digoxin may, however, increase the capacity for physical conditioning. Thus the impairment of extrarenal potassium homeostasis by heart failure and digoxin treatment may be counterbalanced by training.

  1. In Vivo Diode Dosimetry for Imrt Treatments Generated by Pinnacle Treatment Planning System

    International Nuclear Information System (INIS)

    Alaei, Parham; Higgins, Patrick D.; Gerbi, Bruce J.

    2009-01-01

    Dose verification using diodes has been proposed and used for intensity modulated radiation therapy (IMRT) treatments. We have previously evaluated diode response for IMRT deliveries planned with the Eclipse/Helios treatment planning system. The Pinnacle treatment planning system generates plans that are delivered in a different fashion than Eclipse. Whereas the Eclipse-generated segments are delivered in organized progression from one side of each field to the other, Pinnacle-generated segments are delivered in a much more randomized fashion to different areas within the field. This makes diode measurements at a point more challenging because the diode may be exposed fully or partially to multiple small segments during one single field's treatment as opposed to being exposed to very few segments scanning across the diode during an Eclipse-generated delivery. We have evaluated in vivo dosimetry for Pinnacle-generated IMRT plans and characterized the response of the diode to various size segments on phantom. We present results of patient measurements on approximately 300 fields, which show that 76% of measurements agree to within 10% of the treatment-plan generated calculated doses. Of the other 24%, about 11% are within 15% of the calculated dose. Comparison of these with phantom measurements indicates that many of the discrepancies are due to diode positioning on patients and increased diode response at short source-to-surface distances (SSDs), with the remainder attributable to other factors such as segment size and partial irradiation of the diode

  2. Breast conservation treatment of early stage breast cancer: patterns of failure

    Energy Technology Data Exchange (ETDEWEB)

    Leborgne, Felix; Leborgne, Jose H; Ortega, Bettys; Doldan, Raquel; Zubizarreta, Eduardo

    1995-02-15

    Purpose: This study retrospectively assesses the patterns of failure in conservatively treated early stage breast cancer patients by correlating various clinical, pathologic, and treatment-related factors with local, axillary, and distant relapse. Methods and Materials: Between 1973 and 1990, 796 patients (817 breasts) received breast conservation surgery followed by radiotherapy. Local recurrences were counted as events even if they occurred simultaneously or after the appearance of axillary or distant metastases. Results: The 10-year actuarial relative disease-free survival (DFS) rate for T1N0, T2N0, and T1-2N1 was 82%, 71%, and 54%, respectively. Stage N0 patients had a significant DFS advantage over N1 patients (p = 0.02). The 15-year actuarial local recurrence-free rate for T1 and T2 tumors was 82% and 87%, respectively (p = nonsignificant). Univariate analysis identified three significant risk factors for local relapse: (a) 48 breasts with tumors showing an extensive intraductal component had a crude local recurrence rate of 23% compared to 8% for 769 breasts without intraductal component (p 0.0016); (b) the actuarial 10-year local recurrence-free rate for patients under age 40 years was 64% compared to 88% for patients over 40 years (p < 0.0001); (c) the 10-year actuarial local recurrence-free rate for 416 postmenopausal women without adjuvant tamoxifen was 83% compared to 97% for 107 postmenopausal women with tamoxifen (p = 0.0479). Salvage therapy for operable local recurrent patients resulted in a 8-year actuarial DFS rate of 47%, significantly lower than that obtained with primary treatment. The incidence of axillary relapse as the first sign of recurrence was 2%, and could be correlated with the lack of axillary dissection (p < 0.0000005) and primary tumor size (p = 0.03). Radiotherapy to the axilla did not influence axillary relapse. Actuarial 5-year DFS rate after treatment of isolated axillary recurrence was 27%. Axillary failure was a marker for

  3. Breast conservation treatment of early stage breast cancer: patterns of failure

    International Nuclear Information System (INIS)

    Leborgne, Felix; Leborgne, Jose H.; Ortega, Bettys; Doldan, Raquel; Zubizarreta, Eduardo

    1995-01-01

    Purpose: This study retrospectively assesses the patterns of failure in conservatively treated early stage breast cancer patients by correlating various clinical, pathologic, and treatment-related factors with local, axillary, and distant relapse. Methods and Materials: Between 1973 and 1990, 796 patients (817 breasts) received breast conservation surgery followed by radiotherapy. Local recurrences were counted as events even if they occurred simultaneously or after the appearance of axillary or distant metastases. Results: The 10-year actuarial relative disease-free survival (DFS) rate for T1N0, T2N0, and T1-2N1 was 82%, 71%, and 54%, respectively. Stage N0 patients had a significant DFS advantage over N1 patients (p = 0.02). The 15-year actuarial local recurrence-free rate for T1 and T2 tumors was 82% and 87%, respectively (p = nonsignificant). Univariate analysis identified three significant risk factors for local relapse: (a) 48 breasts with tumors showing an extensive intraductal component had a crude local recurrence rate of 23% compared to 8% for 769 breasts without intraductal component (p 0.0016); (b) the actuarial 10-year local recurrence-free rate for patients under age 40 years was 64% compared to 88% for patients over 40 years (p < 0.0001); (c) the 10-year actuarial local recurrence-free rate for 416 postmenopausal women without adjuvant tamoxifen was 83% compared to 97% for 107 postmenopausal women with tamoxifen (p = 0.0479). Salvage therapy for operable local recurrent patients resulted in a 8-year actuarial DFS rate of 47%, significantly lower than that obtained with primary treatment. The incidence of axillary relapse as the first sign of recurrence was 2%, and could be correlated with the lack of axillary dissection (p < 0.0000005) and primary tumor size (p = 0.03). Radiotherapy to the axilla did not influence axillary relapse. Actuarial 5-year DFS rate after treatment of isolated axillary recurrence was 27%. Axillary failure was a marker for

  4. Renal sympathetic denervation for treatment of patients with heart failure: summary of the available evidence.

    Science.gov (United States)

    Nammas, Wail; Koistinen, Juhani; Paana, Tuomas; Karjalainen, Pasi P

    2017-08-01

    Heart failure syndrome results from compensatory mechanisms that operate to restore - back to normal - the systemic perfusion pressure. Sympathetic overactivity plays a pivotal role in heart failure; norepinephrine contributes to maintenance of the systemic blood pressure and increasing preload. Cardiac norepinephrine spillover increases in patients with heart failure; norepinephrine exerts direct toxicity on cardiac myocytes resulting in a decrease of synthetic activity and/or viability. Importantly, cardiac norepinephrine spillover is a powerful predictor of mortality in patients with moderate to severe HF. This provided the rationale for trials that demonstrated survival benefit associated with the use of beta adrenergic blockers in heart failure with reduced ejection fraction. Nevertheless, the MOXCON trial demonstrated that rapid uptitration of moxonidine (inhibitor of central sympathetic outflow) in patients with heart failure was associated with excess mortality and morbidity, despite reduction of plasma norepinephrine. Interestingly, renal norepinephrine spillover was the only independent predictor of adverse outcome in patients with heart failure, in multivariable analysis. Recently, renal sympathetic denervation has emerged as a novel approach for control of blood pressure in patients with treatment-resistant hypertension. This article summarizes the available evidence for the effect of renal sympathetic denervation in the setting of heart failure. Key messages Experimental studies supported a beneficial effect of renal sympathetic denervation in heart failure with reduced ejection fraction. Clinical studies demonstrated improvement of symptoms, and left ventricular function. In heart failure and preserved ejection fraction, renal sympathetic denervation is associated with improvement of surrogate endpoints.

  5. Is virtual reality effective to motivate and raise interest in phobic children toward therapy? A clinical trial study of in vivo with in virtuo versus in vivo only treatment exposure.

    Science.gov (United States)

    St-Jacques, Julie; Bouchard, Stéphane; Bélanger, Claude

    2010-07-01

    The first objective of this study was to assess if a combined treatment with mostly virtual reality-based (in virtuo) exposure increases phobic children's motivation toward therapy compared to children who only receive in vivo exposure. Another objective was the assessment of motivation as a predictor of treatment outcome. Thirty-one DSM-IV-diagnosed arachnophobic participants aged from 8 to 15 years were randomly assigned to 1 of 2 treatment conditions: in vivo exposure alone or in virtuo plus in vivo exposure. Measures of motivation were taken at pretest and at the end of each part of the treatment; some other measures were taken at each session. The "Why Are You in Therapy?" questionnaire for children was the target measure of motivation and the main variable in the study. Outcome measures were taken at pretest, at the end of each part of the treatment, and at the 6-month follow-up. This study was conducted between September 2006 and March 2007. The results showed that children who received in virtuo exposure did not show a higher level of motivation toward their treatment than those who received in vivo exposure, but statistically significant interactions were found for both parts of the treatment. Multiple regression analysis confirmed that motivation was a significant predictor of outcome (P virtual reality did not increase motivation toward psychotherapy. At the end of the second part of therapy, all participants were comparably efficient in facing a live tarantula. These results bear important clinical implications concerning how to use virtual reality with children and concerning motivation of children toward therapy in general. They are discussed in the light of how to present in virtuo therapy to children. (c) Copyright 2010 Physicians Postgraduate Press, Inc.

  6. In vivo testing of the therapeutic efficacy of chloroquine on falciparum malaria infections in Chirundu, Mashonaland West, Zimbabwe.

    Science.gov (United States)

    Barduagni, P; Schwartz, U; Nyamayaro, W; Chauke, T L

    1998-10-01

    To detect the level of the in vivo chloroquine efficacy in falciparum malaria infections, in order to assess the need for change in the management and treatment of uncomplicated malaria. Prospective descriptive study. Chirundu Rural Clinic, Mashonaland West Province. 63 patients confirmed by a positive blood slide for P. falciparum who attended Chirundu clinic, who were eligible for the study and, who also agreed to participate. Frequency of treatment success, early treatment failure and late treatment failure in uncomplicated patients treated with chloroquine. Out of 63 cases enrolled and completely followed up, chloroquine treatment was effective in 54 cases (85.7%) and was not effective in nine cases (14.3%). All treatment failures were successfully treated with sulphadoxine + pyrimethamine (Fansidar) or quinine following the approved guidelines. Chloroquine remains highly effective in the treatment of malaria due to P. falciparum in the Zambezi Valley of Hurungwe district and therefore, has to remain the first line drug. Likewise, guidelines for the use of sulphadoxine + pyrimethamine (Fansidar) or quinine as second line drugs, are adequate to the local situation. Health workers directly supervised the patients when they were swallowing the tablets during the whole course, and this without doubt, indirectly increased the efficacy of chloroquine. It is vital to confirm the malaria diagnosis on the spot appointing microscopists or distributing a limited stock of Parasight-F test.

  7. Cardiac Resynchronization Therapy Defibrillator Treatment in a Child with Heart Failure and Ventricular Arrhythmia

    Directory of Open Access Journals (Sweden)

    Hak Ju Kim

    2016-08-01

    Full Text Available Cardiac resynchronization therapy (CRT is a new treatment for refractory heart failure. However, most patients with heart failure treated with CRT are adults, middle-aged or older with idiopathic or ischemic dilated cardiomyopathy. We treated a 12-year-old boy, who was transferred after cardiac arrest, with dilated cardiomyopathy, left bundle-branch block, and ventricular tachycardia. We performed cardiac resynchronization therapy with a defibrillator (CRT-D. After CRT-D, left ventricular ejection fraction improved from 22% to 4 4% a ssessed by e chocardiog ram 1 year p ostoperatively. On e lectrocardiog ram, Q RS d uration was shortened from 206 to 144 ms. The patient’s clinical symptoms also improved. For pediatric patients with refractory heart failure and ventricular arrhythmia, CRT-D could be indicated as an effective therapeutic option.

  8. Evaluation of the Prevalence of Different Treatment Failure Modes after Crown Lengthening Surgical Procedures

    Directory of Open Access Journals (Sweden)

    Amirreza Babaloo

    2016-07-01

    and a lack of sufficient keratinized gingiva around the tooth was the most frequent reason for early failures of such procedures.   Key words: Crown lengthening surgical procedures; treatment failure; keratinized gingiva;

  9. Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study.

    Science.gov (United States)

    Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

    2017-01-01

    Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.

  10. [Comparison of curative effect of low flow rate plasma exchange combined with hemofiltration for treatment of liver failure].

    Science.gov (United States)

    Yang, Yong-feng; Huang, Ping; Zhang, Ning; Gai, Xiao-dong; Feng, Xiao-ning; Zhong, Yan-dan; Wang, Li-rong; Yang, Yi-jun; Zhao, Wei

    2009-02-01

    To investigate the effect of plasma exchange (PE) combined with hemofiltration (HF) on liver failure. Seventy-seven inpatients with liver failure admitted during January 2006 to August 2007 were randomly assigned to receive PE combined with HF (PE+HF group, 38 cases), or PE alone (PE group, 39 cases). Forty-one inpatients with liver failure who had not received artificial liver support treatment were assigned to serve as control group. The survival rates and biochemical parameters of three groups were compared. There was no significant difference in biochemical parameters before treatment among three groups. Compared with pre-treatment values, albumin (Alb), cholinesterase (ChE) and prothrombin activity (PTA) of both PE group and PE+HF group were significantly increased after treatment, and total bilirubin (TBIL), alanine transaminase (ALT), aspartate transaminase (AST) of both PE group and PE+HF group were significantly decreased after treatment (Prate of PE group, PE+HF group and control group was 48.7% (19/39), 68.4% (26/38), and 29.3% (12/41) respectively. The survival rate of PE+HF group was significantly higher than that of control group (chi(2)=12.11, Prate of recovery of consciousness of patients with hepatic encephalopathy in PE+HF group was higher than that of PE group (42.8% vs. 0, P<0.05). Compared with PE alone, the result was better when it was combined with HF in correction of electrolyte disturbance and acid-base imbalance (19/23 vs. 0/21, P<0.05). Treatment of liver failure by PE combined with HF is safe and effective, and its efficacy is higher than PE alone.

  11. The safety of sacubitril-valsartan for the treatment of chronic heart failure.

    Science.gov (United States)

    Tyler, Jeffrey M; Teerlink, John R

    2017-02-01

    Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril. Areas covered: This review discusses the clinical efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril-valsartan in heart failure with reduced ejection fraction. Expert opinion: Based on the PARADIGM-HF trial, sacubitril-valsartan offers compelling reductions in meaningful clinical endpoints, independent of age or severity of disease. The rate of adverse events was comparable between the enalapril and sacubitril-valsartan groups, although the absolute rates are likely underestimated due to the entry criteria and run-in period. Future trials and post-market surveillance are critical to better understand the risk of angioedema in high risk populations, particularly African-Americans, as well as long-term theoretical risks including the potential for increased cerebral amyloid plaque deposition with possible development of neurocognitive disease. Current trials are underway to evaluate potential benefit in patients with heart failure with preserved ejection fraction.

  12. The Art and Science of Using Diuretics in the Treatment of Heart Failure in Diverse Clinical Settings.

    Science.gov (United States)

    Islam, Md Shahidul

    2018-01-01

    It is important to understand the rationale for appropriate use of different diuretics, alone or in combination, in different heart failure patients, under diverse clinical settings. Clinicians and nurses engaged in heart failure care, must be familiar with different diuretics, their appropriate doses, methods of administration, monitoring of the responses, and the side-effects. Inappropriate use of diuretics, both under-treatment and overtreatment, and poor follow-up can lead to failures, and adverse outcomes. Adequate treatment of congestion, with rather aggressive use of diuretics, is necessary, even if that may worsen renal function temporarily in some patients. Diuretic treatment should later be titrated down, by early recognition of the euvolemic sate, which can be assessed by clinical examination, measurement of the natriuretic peptides, and when possible, echocardiographic estimation of the left ventricular filling pressure. You need to treat patients, who are truly resistant to the loop diuretics, by administering the diuretics as intravenous bolus injection followed by continuous infusion, and/or by sequential nephron blockade by adding the thiazide diuretics. You need to use the diuretics based on a sound understanding of the pathophysiology of the disease process, the pharmacokinetics and pharmacodynamics of the diuretics, even when strong evidences for your choices might be lacking. Some patients may benefit from injection of loop diuretics together with hypertonic saline, and others from injection of loop diuretics with albumin. Patient education, and regular follow up of the treatment of heart failure patients, in out-patient settings are important for reducing the rates of complications, and for reducing the needs for urgent hospitalizations.

  13. Oral Mucosa Model for Electrochemotherapy Treatment of Dog Mouth Cancer: Ex Vivo, In Silico, and In Vivo Experiments.

    Science.gov (United States)

    Suzuki, Daniela O H; Berkenbrock, José A; Frederico, Marisa J S; Silva, Fátima R M B; Rangel, Marcelo M M

    2018-03-01

    Electrochemotherapy (EQT) is a local cancer treatment well established to cutaneous and subcutaneous tumors. Electric fields are applied to biological tissue in order to improve membrane permeability for cytotoxic drugs. This phenomenon is called electroporation or electropermeabilization. Studies have reported that tissue conductivity is electric field dependent. Electroporation numerical models of biological tissues are essential in treatment planning. Tumors of the mouth are very common in dogs. Inadequate EQT treatment of oral tumor may be caused by significant anatomic variations between dogs and tumor position. Numerical models of oral mucosa and tumor allow the treatment planning and optimization of electrodes for each patient. In this work, oral mucosa conductivity during electroporation was characterized by measuring applied voltage and current of ex vivo rats. This electroporation model was used with a spontaneous canine oral melanoma. The model outcomes of oral tumor EQT is applied in different parts of the oral cavity including near bones and the hard palate. The numerical modeling for treatment planning will help the development of new electrodes and increase the EQT effectiveness. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  14. Sorafenib-Associated Heart Failure Complicated by Cardiogenic Shock after Treatment of Advanced Stage Hepatocellular Carcinoma: A Clinical Case Discussion

    Directory of Open Access Journals (Sweden)

    Candace Wu

    2017-01-01

    Full Text Available Background. Sorafenib, an oral tyrosine kinase inhibitor (TKI, targets multiple tyrosine kinase receptors (TKRs involved in angiogenesis and tumor growth. Studies suggest that inhibition of TKR impacts cardiomyocyte survival. Inhibition of VEGF signaling interrupts angiogenesis and is associated with the development of hypertension and compensatory hypertrophy. Compensated hypertrophy ultimately leads to heart failure. Case Description. A 76-year-old man with a past medical history of systolic heart failure due to ischemic cardiomyopathy and stage IIIC hepatocellular carcinoma (HCC presented with symptoms of decompensated heart failure. Four months prior to admission, he was started on sorafenib. Results. Our patient was treated with intravenous furosemide and guideline directed therapy. Clinical status was complicated by the development of low cardiac output and shock requiring inotropic support. Careful titration of heart failure medication led to hemodynamic improvement and discontinuation of dobutamine. Conclusion. Greater awareness of sorafenib cardiotoxicity is essential. As TKI usage grows for treatment of cancers, heart failure-related complications will increase. In our patient, routine heart failure management and cessation of sorafenib led to clinical improvement. Future studies on the treatment of sorafenib cardiotoxicity should be explored further in this unique patient population.

  15. Early treatment with tolvaptan improves diuretic response in acute heart failure with renal dysfunction

    NARCIS (Netherlands)

    Matsue, Yuya; ter Maaten, Jozine M.; Suzuki, Makoto; Torii, Sho; Yamaguchi, Satoshi; Fukamizu, Seiji; Ono, Yuichi; Fujii, Hiroyuki; Kitai, Takeshi; Nishioka, Toshihiko; Sugi, Kaoru; Onishi, Yuko; Noda, Makoto; Kagiyama, Nobuyuki; Satoh, Yasuhiro; Yoshida, Kazuki; van der Meer, Peter; Damman, Kevin; Voors, Adriaan A.; Goldsmith, Steven R.

    2017-01-01

    Background: Poor response to diuretics is associated with worse prognosis in patients with acute heart failure (AHF). We hypothesized that treatment with tolvaptan improves diuretic response in patients with AHF. Methods: We performed a secondary analysis of the AQUAMARINE open-label randomized

  16. Bone density and body composition in chronic renal failure: effects of growth hormone treatment

    NARCIS (Netherlands)

    van der Sluis, I. M.; Boot, A. M.; Nauta, J.; Hop, W. C.; de Jong, M. C.; Lilien, M. R.; Groothoff, J. W.; van Wijk, A. E.; Pols, H. A.; Hokken-Koelega, A. C.; de Muinck Keizer-Schrama, S. M.

    2000-01-01

    Metabolic bone disease and growth retardation are common complications of chronic renal failure (CRF). We evaluated bone mineral density (BMD), bone metabolism, body composition and growth in children with CRF, and the effect of growth hormone treatment (GHRx) on these variables. Thirty-three

  17. Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure.

    Science.gov (United States)

    Ramirez, Claudia E; Okamoto, Luis E; Arnold, Amy C; Gamboa, Alfredo; Diedrich, André; Choi, Leena; Raj, Satish R; Robertson, David; Biaggioni, Italo; Shibao, Cyndya A

    2014-12-01

    The clinical presentation of autonomic failure is orthostatic hypotension. Severely affected patients require pharmacological treatment to prevent presyncopal symptoms or frank syncope. We previously reported in a proof of concept study that pediatric doses of the norepinephrine transporter blockade, atomoxetine, increases blood pressure in autonomic failure patients with residual sympathetic activity compared with placebo. Given that the sympathetic nervous system is maximally activated in the upright position, we hypothesized that atomoxetine would be superior to midodrine, a direct vasoconstrictor, in improving upright blood pressure and orthostatic hypotension-related symptoms. To test this hypothesis, we compared the effect of acute atomoxetine versus midodrine on upright systolic blood pressure and orthostatic symptom scores in 65 patients with severe autonomic failure. There were no differences in seated systolic blood pressure (means difference=0.3 mm Hg; 95% confidence [CI], -7.3 to 7.9; P=0.94). In contrast, atomoxetine produced a greater pressor response in upright systolic blood pressure (means difference=7.5 mm Hg; 95% CI, 0.6 to 15; P=0.03) compared with midodrine. Furthermore, atomoxetine (means difference=0.4; 95% CI, 0.1 to 0.8; P=0.02), but not midodrine (means difference=0.5; 95% CI, -0.1 to 1.0; P=0.08), improved orthostatic hypotension-related symptoms as compared with placebo. The results of our study suggest that atomoxetine could be a superior therapeutic option than midodrine for the treatment of orthostatic hypotension in autonomic failure. © 2014 American Heart Association, Inc.

  18. Clinical experience in treatment of five H1N1 flu patients with respiratory failure with high-frequency oscillatory mechanical ventilation

    Directory of Open Access Journals (Sweden)

    Zhi-gang ZHANG

    2011-08-01

    Full Text Available Objective To investigate the application and safety of high-frequency oscillation ventilation(HFOV in the treatment of patients suffering from H1N1 influenza with respiratory failure.Methods Self-control study was conducted.The treatment of five H1N1 influenza patients with respiratory failure was switched to HFOV after failure of conventional mechanical ventilation(CMV.Blood gas [partial pressure of oxygen(PaO2,partial pressure of carbon dioxide(PCO2,pH],respiratory mechanics indices [oxygen concentration(FiO2,mean airway pressure(Paw,static response(Cst,oxygenation index(PaO2/FiO2] before and after treatment were observed.Lung biopsy and clinical treatment data were also analyzed.Results Oxygenation was improved in 3 patients 6 to 8 hours after HFOV treatment,and marked improvement was observed after 24-48h.48-72h later,HFOV was replaced by CMV,and the patients weaned from mechanical ventilation successfully at 144h.In two patients symptoms were exacerbated after HFOV for 8 hours and the treatment was switched to CMV.Among them one died at 75h,and another one was treated with extracorporeal membrane oxygenation(ECMO and died at 145h.Conclusions HFOV can significantly improve the outcome of H1N1 flu patients with respiratory failure.The sequential treatment with HFOV followed by CMV can reduce complications and mortality.

  19. Failure to thrive in childhood.

    Science.gov (United States)

    Nützenadel, Walter

    2011-09-01

    Failure to thrive impairs children's weight gain and growth, their defenses against infection, and their psychomotor and intellectual development. This paper is a review of pertinent articles that were published from 1995 to October 2010 and contained the terms "failure to thrive", "underweight", "malnutrition", "malabsorption", "maldigestion" and "refeeding syndrome". The articles were retrieved by a search in the PubMed and Cochrane Library databases. In developed countries, failure to thrive is usually due to an underlying disease. The degree of malnutrition is assessed with anthropometric techniques. For each patient, the underlying disease must be identified and the mechanism of failure to thrive understood, so that proper medical and nutritional treatment can be provided. Nutritional treatment involves either giving more food, or else raising the caloric density of the patient's food. Liquid formulas can be given as a supplement to normal meals or as balanced or unbalanced tube feeds; they can be given orally, through a nasogastric tube, or through a gastrostomy tube. Severely malnourished children with poor oral intake should be treated with parenteral nutrition. To avoid refeeding syndrome in severely malnourished children, food intake should be increased slowly at first, and phosphate, magnesium, and potassium supplements should be given. The proper treatment of failure to thrive in childhood consists of treatment of the underlying illness, combined with nutritional treatment that addresses the mechanism of the accompanying failure to thrive.

  20. [Comorbidities of heart failure: sleep apnea].

    Science.gov (United States)

    Woehrle, H; Oldenburg, O; Stadler, S; Arzt, M

    2018-05-01

    Since sleep apnea often occurs in heart failure, physicians regularly need to decide whether further diagnostic procedures and/or treatment are required. Which types of sleep apnea occur in heart failure patients? When is treatment needed? Which treatments and treatment goals are appropriate? Clinical trials and guidelines as well as their implementation in clinical practice are discussed. At least 40% of patients with heart failure, both with reduced and preserved left ventricular ejection fraction (HFrEF and HFpEF, respectively), suffer from relevant sleep apnea. In heart failure patients both obstructive and central sleep apnea are associated with increased mortality. In HFrEF as well as in HFpEF patients with obstructive sleep apnea, treatment with continuous positive airway pressure (CPAP) achieves symptomatic and functional improvements. In patients with HFpEF, positive airway pressure treatment of central sleep apnea may be beneficial. In patients with HFrEF and left ventricular ejection fraction ≤45%, adaptive servoventilation is contraindicated. Sleep apnea is highly prevalent in heart failure patients and its treatment in specific patient groups can improve symptoms and functional outcomes. Thus, testing for sleep apnea is recommended.

  1. Exploration of flexible phenylpropylurea scaffold as novel cardiac myosin activators for the treatment of systolic heart failure.

    Science.gov (United States)

    Manickam, Manoj; Jalani, Hitesh B; Pillaiyar, Thanigaimalai; Sharma, Niti; Boggu, Pulla Reddy; Venkateswararao, Eeda; Lee, You-Jung; Jeon, Eun-Seok; Jung, Sang-Hun

    2017-07-07

    A series of flexible urea derivatives have been synthesized and demonstrated as selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3-phenylpropyl)urea (1, cardiac myosin ATPase activation at 10 μM = 51.1%; FS = 18.90; EF = 12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase activation = 53.3%; FS = 30.04; EF = 18.27) showed significant activity in vitro and in vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1-(3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin ATPase activation = 81.4%; FS = 20.50; EF = 13.10), and morpholine moiety viz., 1-(2-morpholinoethyl)-3-(3-phenylpropyl)urea (21, cardiac myosin ATPase activation = 44.0%; FS = 24.79; EF = 15.65), proved to be efficient to activate the cardiac myosin. The potent compounds 1, 9, 14 and 21 were found to be selective for cardiac myosin over skeletal and smooth myosins. Thus, these urea derivatives are potent scaffold to develop as a newer cardiac myosin activator for the treatment of systolic heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Effect of heart failure reversal treatment as add-on therapy in patients with chronic heart failure: A randomized, open-label study.

    Science.gov (United States)

    Sane, Rohit; Aklujkar, Abhijeet; Patil, Atul; Mandole, Rahul

    The present study was designed to evaluate effect of heart failure reversal therapy (HFRT) using herbal procedure (panchakarma) and allied therapies, as add-on to standard CHF treatment (SCT) in chronic heart failure (CHF) patients. This open-label, randomized study conducted in CHF patients (aged: 25-65 years, ejection fraction: 30-65%), had 3-phases: 1-week screening, 6-week treatment (randomized [1:1] to HFRT+SCT or SCT-alone) and follow-up (12-week). Twice weekly HFRT (60-75min) consisting of snehana (external oleation), swedana (passive heat therapy), hrudaydhara (concoction dripping treatment) and basti (enema) was administered. Primary endpoints included evaluation of change in metabolic equivalents of task (MET) and peak oxygen uptake (VO 2peak ) from baseline, at end of 6-week treatment and follow-up at week-18 (non-parametric rank ANCOVA analysis). Safety and quality of life (QoL) was assessed. Seventy CHF patients (n=35, each treatment-arm; mean [SD] age: 53.0 [8.6], 80% men) were enrolled in the study. All patients completed treatment phase. Add-on HFRT caused a significant increase in METs (least square mean difference [LSMD], 6-week: 1.536, p=0.0002; 18-week: -1.254, p=0.0089) and VO 2peak (LSMD, 6-week: -5.52, p=0.0002; 18-week: -4.517, p=0.0089) as compared with SCT-alone. Results were suggestive of improved functional capacity in patients with HFRT (QoL; Mean [SD] HFRT+SCT vs. SCT-alone; 6-week: -0.44 [0.34] vs. -0.06 [0.25], p<0.0001 and 18-week: -0.53 [0.35] vs. -0.29 [0.26], p=0.0013). Seven treatment-emergent adverse events (mild severity) were reported in HFRT-arm. Findings of this study highlight therapeutic efficacy of add-on HFRT vs. SCT-alone in CHF patients. The non-invasive HFRT showed no safety concerns. Copyright © 2016. Published by Elsevier B.V.

  3. Association of the Endobiont Double-Stranded RNA Virus LRV1 With Treatment Failure for Human Leishmaniasis Caused by Leishmania braziliensis in Peru and Bolivia

    Science.gov (United States)

    Adaui, Vanessa; Lye, Lon-Fye; Akopyants, Natalia S.; Zimic, Mirko; Llanos-Cuentas, Alejandro; Garcia, Lineth; Maes, Ilse; De Doncker, Simonne; Dobson, Deborah E.; Arevalo, Jorge; Dujardin, Jean-Claude; Beverley, Stephen M.

    2016-01-01

    Cutaneous and mucosal leishmaniasis, caused in South America by Leishmania braziliensis, is difficult to cure by chemotherapy (primarily pentavalent antimonials [SbV]). Treatment failure does not correlate well with resistance in vitro, and the factors responsible for treatment failure in patients are not well understood. Many isolates of L. braziliensis (>25%) contain a double-stranded RNA virus named Leishmaniavirus 1 (LRV1), which has also been reported in Leishmania guyanensis, for which an association with increased pathology, metastasis, and parasite replication was found in murine models. Here we probed the relationship of LRV1 to drug treatment success and disease in 97 L. braziliensis–infected patients from Peru and Bolivia. In vitro cultures were established, parasites were typed as L. braziliensis, and the presence of LRV1 was determined by reverse transcription–polymerase chain reaction, followed by sequence analysis. LRV1 was associated significantly with an increased risk of treatment failure (odds ratio, 3.99; P = .04). There was no significant association with intrinsic SbV resistance among parasites, suggesting that treatment failure arises from LRV1-mediated effects on host metabolism and/or parasite survival. The association of LRV1 with clinical drug treatment failure could serve to guide more-effective treatment of tegumentary disease caused by L. braziliensis. PMID:26123565

  4. Case report: failure under azithromycin treatment in a case of bacteremia due to Salmonella enterica Paratyphi A.

    Science.gov (United States)

    Kobayashi, Tetsuro; Hayakawa, Kayoko; Mawatari, Momoko; Mezaki, Kazuhisa; Takeshita, Nozomi; Kutsuna, Satoshi; Fujiya, Yoshihiro; Kanagawa, Shuzo; Ohmagari, Norio; Kato, Yasuyuki; Morita, Masatomo

    2014-07-20

    Limited information is available regarding the clinical efficacy of azithromycin for the treatment of enteric fever due to fluoroquinolone-resistant Salmonella Typhi and Salmonella Paratyphi among travelers returning to their home countries. We report a case of a 52-year-old Japanese man who returned from India, who developed a fever of 39°C with no accompanying symptoms 10 days after returning to Japan from a 1-month business trip to Delhi, India. His blood culture results were positive for Salmonella Paratyphi A. He was treated with 14 days of ceftriaxone, after which he remained afebrile for 18 days before his body temperature again rose to 39°C with no apparent symptoms. He was then empirically given 500 mg of azithromycin, but experienced clinical and microbiological failure of azithromycin treatment for enteric fever due to Salmonella Paratyphi A. However, the minimum inhibitory concentration (MIC) of azithromycin was not elevated (8 mg/L). He was again given ceftriaxone for 14 days with no signs of recurrence during the follow-up. There are limited data available for the treatment of enteric fever using azithromycin in travelers from developed countries who are not immune to the disease, and thus, careful follow-up is necessary. In our case, the low azithromycin dose might have contributed the treatment failure. Additional clinical data are needed to determine the rate of success, MIC, and contributing factors for success and/or failure of azithromycin treatment for both Salmonella Typhi and Salmonella Paratyphi infections.

  5. Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis

    Science.gov (United States)

    Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma

    2018-01-01

    Background Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. Methods We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. Results We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. Conclusion The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. PMID:28780577

  6. Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy

    Directory of Open Access Journals (Sweden)

    Bacha Tigist

    2012-08-01

    Full Text Available Abstract Background The emergence of resistance to first line antiretroviral therapy (ART regimen leads to the need for more expensive and less tolerable second line drugs. Hence, it is essential to identify and address factors associated with an increased probability of first line ART regimen failure. The objective of this article is to report on the predictors of first line ART regimen failure, the detection rate of ART regime failure, and the delay in switching to second line ART drugs. Methods A retrospective cohort study was conducted from 2005 to 2011. All HIV infected children under the age of 15 who took first line ART for at least six months at the four major hospitals of Addis Ababa, Ethiopia were included. Data were collected, entered and analyzed using Epi info/ENA version 3.5.1 and SPSS version 16. The Cox proportional-hazard model was used to assess the predictors of first line ART failure. Results Data of 1186 children were analyzed. Five hundred seventy seven (48.8% were males with a mean age of 6.22 (SD = 3.10 years. Of the 167(14.1% children who had treatment failure, 70 (5.9% had only clinical failure, 79 (6.7% had only immunologic failure, and 18 (1.5% had both clinical and immunologic failure. Patients who had height for age in the third percentile or less at initiation of ART were found to have higher probability of ART treatment failure [Adjusted Hazard Ratio (AHR, 3.25 95% CI, 1.00-10.58]. Patients who were less than three years old [AHR, 1.85 95% CI, 1.24-2.76], chronic diarrhea after initiation of antiretroviral treatment [AHR, 3.44 95% CI, 1.37-8.62], ART drug substitution [AHR, 1.70 95% CI, 1.05-2.73] and base line CD4 count below 50 cells/mm3 [AHR, 2.30 95% CI, 1.28-4.14] were also found to be at higher risk of treatment failure. Of all the 167 first line ART failure cases, only 24 (14.4% were switched to second line ART with a mean delay of 24 (SD = 11.67 months. The remaining 143 (85.6% cases were diagnosed

  7. The role of the renin-angiotensin-aldosterone system in heart failure

    Directory of Open Access Journals (Sweden)

    Thomas Unger

    2004-03-01

    Full Text Available Activity of the renin-angiotensin-aldosterone system (RAAS is increased in patients with heart failure, and its maladaptive mechanisms may lead to adverse effects such as cardiac remodelling and sympathetic activation. Elevated renin activity has been demonstrated in patients with dilated cardiomyopathy. (Third-generation synthetic non-peptide renin inhibitors, with more favourable properties than earlier renin inhibitors, lower ambulatory blood pressure and may have a role to play in other cardiovascular disease. Chymase, a protease inhibitor stored in mast cells that generates angiotensin II (Ang II (in addition to angiotensin-converting enzyme [ACE], has been linked to extracellular matrix remodelling in heart failure. Again, chymase inhibitors have been developed to investigate its functions in vitro and in vivo. Bradykinin is thought to contribute to the cardioprotective effect of ACE inhibition through modification of nitric oxide release, calcium handling and collagen accumulation. Ang II is believed to influence a number of molecular and structural changes in the heart, mostly mediated through the AT1-receptor. The importance of the RAAS in heart failure is shown by the survival benefit conferred by treatment with ACE inhibitors.

  8. HIV reservoirs and immune surveillance evasion cause the failure of structured treatment interruptions: a computational study.

    Directory of Open Access Journals (Sweden)

    Emiliano Mancini

    Full Text Available Continuous antiretroviral therapy is currently the most effective way to treat HIV infection. Unstructured interruptions are quite common due to side effects and toxicity, among others, and cannot be prevented. Several attempts to structure these interruptions failed due to an increased morbidity compared to continuous treatment. The cause of this failure is poorly understood and often attributed to drug resistance. Here we show that structured treatment interruptions would fail regardless of the emergence of drug resistance. Our computational model of the HIV infection dynamics in lymphoid tissue inside lymph nodes, demonstrates that HIV reservoirs and evasion from immune surveillance themselves are sufficient to cause the failure of structured interruptions. We validate our model with data from a clinical trial and show that it is possible to optimize the schedule of interruptions to perform as well as the continuous treatment in the absence of drug resistance. Our methodology enables studying the problem of treatment optimization without having impact on human beings. We anticipate that it is feasible to steer new clinical trials using computational models.

  9. Impact of medical treatment on lung diffusion capacity in elderly patients with heart failure. Baseline characteristics and 1-year follow up after medical treatment

    DEFF Research Database (Denmark)

    Petersen, Claus Leth; Kjaer, Andreas

    2005-01-01

    treatment (baseline) and after 1 year of treatment with diuretics and ACE-inhibitors/angiotensin-II receptor antagonists. Age- and gender-matched healthy volunteers were included as control group. RESULTS: (mean+/-S.E.M.): K(CO) at baseline was 0.95+/-0.06 and 1.25+/-0.04 mmol/min x kPa/l in HF patients......AIM: The aim of this investigation was (1) to study the effect of untreated chronic heart failure (CHF) on alveolar membrane diffusion capacity (transfer coefficient, K(CO)) in elderly patients and (2) to study the impact of the standard regime of medical treatment with diuretics and ACE......-inhibitor/angiotensin-II receptor antagonists on K(CO) in these patients. METHODS: Non-medicated patients (except for diuretics) with symptoms of heart failure (NYHA II-III) and echocardiographically estimated left ventricular ejection fraction (LVEF)

  10. Prediction factors for failure to seek treatment following traumatic dental injuries to primary teeth

    Directory of Open Access Journals (Sweden)

    Ramon Targino Firmino

    2014-06-01

    Full Text Available The objective of this study was to evaluate prediction factors for failure to seek treatment following a traumatic dental injury (TDI to primary teeth among preschool children in the city of Campina Grande, Brazil. A cross-sectional study was carried out involving 277 children 3 to 5 years of age, with TDI, enrolled in public and private preschools. Parents filled out a form addressing demographic data and whether or not they had sought treatment. Clinical examinations were performed by three dentists who had undergone a calibration exercise (Kappa: 0.85 to 0.90 for the evaluation of TDI. Bivariate and multivariate Poisson regression models were constructed (α = 5%. Enamel fracture was the most prevalent type of TDI (48.7% and the upper central incisors were the most affected teeth (88.4%. The frequency of seeking dental treatment was low (9.7%. The following variables were associated with failure to seek treatment following TDI: a household income greater than one minimum wage (PR = 1.170; 95%CI 1.018-1.341, parents/caregivers’ perception of a child’s oral health as poor (PR = 1.100; 95%CI 1.026-1.176, and the non-perception of TDI by parents/caregivers (PR = 1.250; 95%CI 1.142-1.360. In the present study, the frequency of seeking treatment following TDI was low, and parents/caregivers with a higher income, a poor perception of their child’s oral health and a lack of awareness regarding the trauma were more likely to fail to seek treatment following TDI to primary teeth.

  11. Failure mode and effect analysis oriented to risk-reduction interventions in intraoperative electron radiation therapy: the specific impact of patient transportation, automation, and treatment planning availability.

    Science.gov (United States)

    López-Tarjuelo, Juan; Bouché-Babiloni, Ana; Santos-Serra, Agustín; Morillo-Macías, Virginia; Calvo, Felipe A; Kubyshin, Yuri; Ferrer-Albiach, Carlos

    2014-11-01

    Industrial companies use failure mode and effect analysis (FMEA) to improve quality. Our objective was to describe an FMEA and subsequent interventions for an automated intraoperative electron radiotherapy (IOERT) procedure with computed tomography simulation, pre-planning, and a fixed conventional linear accelerator. A process map, an FMEA, and a fault tree analysis are reported. The equipment considered was the radiance treatment planning system (TPS), the Elekta Precise linac, and TN-502RDM-H metal-oxide-semiconductor-field-effect transistor in vivo dosimeters. Computerized order-entry and treatment-automation were also analyzed. Fifty-seven potential modes and effects were identified and classified into 'treatment cancellation' and 'delivering an unintended dose'. They were graded from 'inconvenience' or 'suboptimal treatment' to 'total cancellation' or 'potentially wrong' or 'very wrong administered dose', although these latter effects were never experienced. Risk priority numbers (RPNs) ranged from 3 to 324 and totaled 4804. After interventions such as double checking, interlocking, automation, and structural changes the final total RPN was reduced to 1320. FMEA is crucial for prioritizing risk-reduction interventions. In a semi-surgical procedure like IOERT double checking has the potential to reduce risk and improve quality. Interlocks and automation should also be implemented to increase the safety of the procedure. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Failures in the rehabilitation treatment with removable partial dentures.

    Science.gov (United States)

    Benso, Bruna; Kovalik, Ana C; Jorge, Janaina H; Campanha, Nara H

    2013-11-01

    Despite being functional and having aesthetic benefits, the acceptance of patients regarding the use of removable partial dentures (RPDs) has been low. In part, this is due to the deleterious effects that causes discomfort to the patient. Success depends not only on the care expended by the patient, including daily care and oral hygiene, but also on common goals set by their professional and clinical staff, aiming beyond aesthetics, to incorporate issues of functionality and the well-being of patients. For rehabilitation treatment with RPDs to reach the desired level of success without damaging the support structure, all the steps (diagnose, cavity preparation, adaptation of the metal structures, functional of distal extension and posterior follow-up) in the rehabilitative treatment should be carefully developed. A literature review was carried out, searching through MEDLINE (PubMed) articles published between 1965 and December 2012 including clinical trials and reviews about the use of RPDs. This study describes factors that lead to failures and complications in oral rehabilitation through the use of RPDs and suggests possible solutions.

  13. The usefulness of treatment evaluation of severe heart failure by ECG-gated myocardial SPECT

    International Nuclear Information System (INIS)

    Ohkoshi, Nobuyuki; Watanabe, Shingo; Matsumoto, Tooru

    2011-01-01

    Our purpose of study was to investigate the usefulness of treatment evaluation of severe heart failure by Electrocardiogram (ECG)-gated myocardial single photon emission computed tomography (SPECT). We evaluated the cardiac function in the case of severe heart failure by gated SPECT and compared it with the cardiac function obtained by left ventriculography (LVG), echocardiography, cardiac MRI, and B-type natriuretic peptide (BNP) values. We investigated the correlation of ejection fraction (EF), time lag of wall motion between the septal and lateral walls of the left ventricle for cardiac resynchronization therapy (CRT) and wall thickening (WT). We classified the left ventricular (LV) into basal, middle and apical areas for comparison of WT. We investigated the effect of a perfusion defect score in these comparisons. The gated SPECT results were correlated with comparative subjects in EF. The results were correlated with MRI on the middle area of the LV in the comparison of WT. We thought it was possible that there was an effect from a perfusion defect score in a time lag comparison of wall motion. Treatment evaluation of severe heart failure by gated SPECT is useful, because it is able to obtain three-dimensional cardiac function analysis, and it offers objectivity and reproducible quantitative evaluation. At the same time, perfusion SPECT is helpful for CRT and LV-plasty. (author)

  14. Incidence and risk factors of first-line antiretroviral treatment failure among human immunodeficiency virus-infected children in Amhara regional state, Ethiopia: a retrospective follow-up study.

    Science.gov (United States)

    Sisay, Malede Mequanent; Ayele, Tadesse Awoke; Gelaw, Yalemzewod Assefa; Tsegaye, Adino Tesfahun; Gelaye, Kassahun Alemu; Melak, Melkitu Fentie

    2018-04-05

    This study aimed to assess the incidence and risk factors of treatment failure among HIV/AIDS-infected children who were on antiretroviral therapy (ART) in Amhara National Regional State, Ethiopia. A retrospective follow-up study was conducted from January 2010 to March 2016. A total of 824 children under the age of 15 who had started ART were included in the study. Data were collected from children's medical charts and ART registration logbook using a standard checklist. A Weibull regression model was used to identify the risk factors of treatment failure. Adjusted HRs (AHRs) with 95% CIs were used to declare statistical significance. The mean (±SD) age of the children was 6.4±3.6 years, with a median (IQR) follow-up of 30.5 (14.6-51.4) months. Sixty-three children (7.7%, 95% CI 5.8 to 9.5) developed treatment failure, 17 (27.0%) of whom were immunological and 46 (73.0%) were clinical failures. The incidence rate of treatment failure was 22.1/10 000 person-months. The cumulative probability of failure was 0.4, with 28 562.5 person-month observations. Lack of disclosure (AHR=4. 4, 95% CI 1.8 to 11.3), opportunistic infections during initiation of ART (AHR=2.3, 95% CI 1.3 to 4.1) and prolonged follow-up (AHR=0.06, 95% CI 0.02 to 0.18) were the main predictors of treatment failure. This study revealed that the incidence of treatment failure remains a significant public health concern in Ethiopia. Undisclosed HIV status to children, the presence of opportunistic infections during initiation of ART and prolonged follow-up were found to be the main predictors of treatment failure. Hence, early detection of treatment failure and further studies on viral monitoring need to be considered. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Failure of operative treatment for glenohumeral instability: etiology and management.

    Science.gov (United States)

    Shah, Apurva S; Karadsheh, Mark S; Sekiya, Jon K

    2011-05-01

    Failure of primary shoulder stabilization procedures is often related to uncorrected anatomic pathology. Orthopaedic surgeons must recognize excessive capsular laxity or large glenohumeral bone defects preoperatively to avoid recurrence of instability. When history, physical examination, and radiographic evaluation are used in conjunction, patients at risk for failure can be identified. The instability severity index score permits precise identification of patients at risk. When treating patients in whom prior surgical intervention has failed, the success of revision procedures correlates to the surgeon's ability to identify the essential pathology and use lesion-specific treatment strategies. Revision procedures remain technically demanding. Keen preoperative and intraoperative judgment is required to avoid additional recurrence of instability after revision procedures, particularly because results deteriorate with each successive operation. Glenoid or humeral defects with greater than 25% bone loss compromise stability provided through the mechanism of concavity compression. These defects must be specifically addressed to avoid recurrence of instability. We prefer anatomic reconstruction techniques combined with capsulolabral repair and, if bone defects are present, anatomic reconstruction with osteochondral allograft. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  16. Quantifying the performance of in vivo portal dosimetry in detecting four types of treatment parameter variations

    International Nuclear Information System (INIS)

    Bojechko, C.; Ford, E. C.

    2015-01-01

    Purpose: To quantify the ability of electronic portal imaging device (EPID) dosimetry used during treatment (in vivo) in detecting variations that can occur in the course of patient treatment. Methods: Images of transmitted radiation from in vivo EPID measurements were converted to a 2D planar dose at isocenter and compared to the treatment planning dose using a prototype software system. Using the treatment planning system (TPS), four different types of variability were modeled: overall dose scaling, shifting the positions of the multileaf collimator (MLC) leaves, shifting of the patient position, and changes in the patient body contour. The gamma pass rate was calculated for the modified and unmodified plans and used to construct a receiver operator characteristic (ROC) curve to assess the detectability of the different parameter variations. The detectability is given by the area under the ROC curve (AUC). The TPS was also used to calculate the impact of the variations on the target dose–volume histogram. Results: Nine intensity modulation radiation therapy plans were measured for four different anatomical sites consisting of 70 separate fields. Results show that in vivo EPID dosimetry was most sensitive to variations in the machine output, AUC = 0.70 − 0.94, changes in patient body habitus, AUC = 0.67 − 0.88, and systematic shifts in the MLC bank positions, AUC = 0.59 − 0.82. These deviations are expected to have a relatively small clinical impact [planning target volume (PTV) D 99 change <7%]. Larger variations have even higher detectability. Displacements in the patient’s position and random variations in MLC leaf positions were not readily detectable, AUC < 0.64. The D 99 of the PTV changed by up to 57% for the patient position shifts considered here. Conclusions: In vivo EPID dosimetry is able to detect relatively small variations in overall dose, systematic shifts of the MLC’s, and changes in the patient habitus. Shifts in the patient

  17. In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Gang; He, Yunfeng; Wu, Xiaohou; Zhang, Yao [Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing (China); Luo, Chunli [Department of Laboratory Medicine, Chongqing Medical University, Chongqing (China); Jing, Peng [Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing (China)

    2012-07-13

    Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer. Key words: Single-walled carbon nanotubes; Bladder cancer; Drug vehicle; THP; Intravesical chemotherapy.

  18. Quantifying the performance of in vivo portal dosimetry in detecting four types of treatment parameter variations

    Energy Technology Data Exchange (ETDEWEB)

    Bojechko, C.; Ford, E. C., E-mail: eford@uw.edu [Department of Radiation Oncology, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195 (United States)

    2015-12-15

    Purpose: To quantify the ability of electronic portal imaging device (EPID) dosimetry used during treatment (in vivo) in detecting variations that can occur in the course of patient treatment. Methods: Images of transmitted radiation from in vivo EPID measurements were converted to a 2D planar dose at isocenter and compared to the treatment planning dose using a prototype software system. Using the treatment planning system (TPS), four different types of variability were modeled: overall dose scaling, shifting the positions of the multileaf collimator (MLC) leaves, shifting of the patient position, and changes in the patient body contour. The gamma pass rate was calculated for the modified and unmodified plans and used to construct a receiver operator characteristic (ROC) curve to assess the detectability of the different parameter variations. The detectability is given by the area under the ROC curve (AUC). The TPS was also used to calculate the impact of the variations on the target dose–volume histogram. Results: Nine intensity modulation radiation therapy plans were measured for four different anatomical sites consisting of 70 separate fields. Results show that in vivo EPID dosimetry was most sensitive to variations in the machine output, AUC = 0.70 − 0.94, changes in patient body habitus, AUC = 0.67 − 0.88, and systematic shifts in the MLC bank positions, AUC = 0.59 − 0.82. These deviations are expected to have a relatively small clinical impact [planning target volume (PTV) D{sub 99} change <7%]. Larger variations have even higher detectability. Displacements in the patient’s position and random variations in MLC leaf positions were not readily detectable, AUC < 0.64. The D{sub 99} of the PTV changed by up to 57% for the patient position shifts considered here. Conclusions: In vivo EPID dosimetry is able to detect relatively small variations in overall dose, systematic shifts of the MLC’s, and changes in the patient habitus. Shifts in the

  19. Redox-dependent regulation of the Na⁺-K⁺ pump: new twists to an old target for treatment of heart failure.

    Science.gov (United States)

    Liu, Chia-Chi; Fry, Natasha A S; Hamilton, Elisha J; Chia, Karin K M; Garcia, Alvaro; Karimi Galougahi, Keyvan; Figtree, Gemma A; Clarke, Ronald J; Bundgaard, Henning; Rasmussen, Helge H

    2013-08-01

    By the time it was appreciated that the positive inotropic effect of cardiac glycosides is due to inhibition of the membrane Na(+)-K(+) pump, glycosides had been used for treatment of heart failure on an empiric basis for ~200 years. The subsequent documentation of their lack of clinical efficacy and possible harmful effect largely coincided with the discovery that a raised Na(+) concentration in cardiac myocytes plays an important role in the electromechanical phenotype of heart failure syndromes. Consistent with this, efficacious pharmacological treatments for heart failure have been found to stimulate the Na(+)-K(+) pump, effectively the only export route for intracellular Na(+) in the heart failure. A paradigm has emerged that implicates pump inhibition in the raised Na(+) levels in heart failure. It invokes protein kinase-dependent activation of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) and glutathionylation, a reversible oxidative modification, of the Na(+)-K(+) pump molecular complex that inhibits its activity. Since treatments of proven efficacy reverse the oxidative Na(+)-K(+) pump inhibition, the pump retains its status as a key pharmacological target in heart failure. Its role as a target is well integrated with the paradigms of neurohormonal abnormalities, raised myocardial oxidative stress and energy deficiency implicated in the pathophysiology of the failing heart. We propose that targeting oxidative inhibition of the pump is useful for the exploration of future treatment strategies. This article is part of a Special Issue entitled "Na(+)Regulation in Cardiac Myocytes". Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Mechanical circulatory treatment of advanced heart failure

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Vase, Henrik; Gjedsted, Jakob

    2016-01-01

    Heart failure is one of the most common causes of morbidity and mortality worldwide. When patients cease to respond adequately to optimal medical therapy mechanical circulatory support has been promising. The advent of mechanical circulatory support devices has allowed significant improvements...... in patient survival and quality of life for those with advanced or end-stage heart failure. We provide a general overview of current mechanical circulatory support devices encompassing options for both short- and long-term ventricular support....

  1. Adaptive servo ventilation for central sleep apnoea in heart failure : SERVE-HF on-treatment analysis

    NARCIS (Netherlands)

    Woehrle, Holger; Cowie, Martin R.; Eulenburg, Christine; Suling, Anna; Angermann, Christiane; d'Ortho, Marie-Pia; Erdmann, Erland; Levy, Patrick; Simonds, Anita K.; Somers, Virend K.; Zannad, Faiez; Teschler, Helmut; Wegscheider, Karl

    2017-01-01

    This on-treatment analysis was conducted to facilitate understanding of mechanisms underlying the increased risk of all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction and predominant central sleep apnoea randomised to adaptive servo ventilation versus the

  2. Low-Dose Involved-Field Radiation in the Treatment of Non-Hodgkin Lymphoma: Predictors of Response and Treatment Failure

    Energy Technology Data Exchange (ETDEWEB)

    Russo, Andrea L., E-mail: alrusso@partners.org [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Chen, Yu-Hui [Biostatistics Core, Dana Farber Cancer Institute, Boston, Massachusetts (United States); Martin, Neil E.; Vinjamoori, Anant; Luthy, Sarah K. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Freedman, Arnold [Department of Hematologic Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Michaelson, Evan M.; Silver, Barbara; Mauch, Peter M.; Ng, Andrea K. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2013-05-01

    Purpose: To investigate clinical and pathologic factors significant in predicting local response and time to further treatment after low-dose involved-field radiation therapy (LD-IFRT) for non-Hodgkin lymphoma (NHL). Methods and Materials: Records of NHL patients treated at a single institution between April 2004 and September 2011 were retrospectively reviewed. Low-dose involved-field radiation therapy was given as 4 Gy in 2 fractions over 2 consecutive days. Treatment response and disease control were determined by radiographic studies and/or physical examination. A generalized estimating equation model was used to assess the effect of tumor and patient characteristics on disease response. A Cox proportional hazards regression model was used to assess time to further treatment. Results: We treated a total of 187 sites in 127 patients with LD-IFRT. Histologies included 66% follicular, 9% chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma, 10% marginal zone, 6% mantle cell lymphoma (MCL), and 8% other. Median follow-up time was 23.4 months (range, 0.03-92.2 months). The complete response, partial response, and overall response rates were 57%, 25%, and 82%, respectively. A CLL histology was associated with a lower response rate (odds ratio 0.2, 95% confidence interval 0.1-0.5, P=.02). Tumor size, site, age at diagnosis, and prior systemic therapy were not associated with response. The median time to first recurrence was 13.6 months. Those with CLL and age ≤50 years at diagnosis had a shorter time to further treatment for local failures (hazard ratio [HR] 3.63, P=.01 and HR 5.50, P=.02, respectively). Those with CLL and MCL had a shorter time to further treatment for distant failures (HR 11.1 and 16.3, respectively, P<.0001). Conclusions: High local response rates were achieved with LD-IFRT across most histologies. Chronic lymphocytic leukemia and MCL histologies and age ≤50 years at diagnosis had a shorter time to further treatment after LD-IFRT.

  3. Common-Cause Failure Analysis in Event Assessment

    International Nuclear Information System (INIS)

    Rasmuson, D.M.; Kelly, D.L.

    2008-01-01

    This paper reviews the basic concepts of modeling common-cause failures (CCFs) in reliability and risk studies and then applies these concepts to the treatment of CCF in event assessment. The cases of a failed component (with and without shared CCF potential) and a component being unavailable due to preventive maintenance or testing are addressed. The treatment of two related failure modes (e.g. failure to start and failure to run) is a new feature of this paper, as is the treatment of asymmetry within a common-cause component group

  4. Experimental cystic echinococcosis therapy: In vitro and in vivo combined 5-fluorouracil/albendazole treatment.

    Science.gov (United States)

    Pensel, Patricia E; Elissondo, Natalia; Gambino, Guillermo; Gamboa, Gabriela Ullio; Benoit, J P; Elissondo, María C

    2017-10-15

    Human cystic echinococcosis is a zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato (s. l.). Although benzimidazole compounds such as albendazole (ABZ) and mebendazole have been the cornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence, new strategies are required to improve treatment of human cystic echinococcosis. The goals of the current study were as follows: (i) to evaluate the in vitro efficacy of the 5-fluorouracil (5-FU) and ABZ combination against E. granulosus s. l. protoscoleces and cysts, (ii) to compare the clinical efficacy of 5-FU alone or in combination with ABZ in infected mice. The combination of 5-FU+ABZ had a stronger in vitro effect against larval stage than that did both drugs alone. Even at the lowest concentration of 5-FU+ABZ combination (1μg/ml), the reduction of the viability of protoscoleces and cysts was greater than that observed with drugs alone at 10μg/ml. The results were confirmed at the ultrastructural level by scanning electron microscopy. These data helped to justify the in vivo investigations assessing the therapeutic potential of the combination of 5-FU and ABZ suspension in CF-1 mice infected with E. granulosus sensu stricto (s. s.) metacestodes. Treatment with 5-FU (10mg/kg) or 5-FU (10mg/kg) + ABZ suspension (5mg/kg) reduced the weight of cysts recovered from mice compared with control groups. Interestingly, the effect of 5-FU given weekly for 5 consecutive weeks was comparable to that observed with ABZ suspension under a daily schedule during 30days. Co-administration of 5-FU with ABZ did not enhance the in vivo efficacy of drugs alone calculated in relation to cysts weights. However, the combination provoked greater ultrastructural alterations compared to the monotherapy. In conclusion, we demonstrated the efficacy of 5-FU either alone or co-administrated with ABZ against murine experimental cystic echinococcosis. Since 5-FU treatments

  5. Metabolomics - A wide-open door to personalized treatment in chronic heart failure?

    Science.gov (United States)

    Marcinkiewicz-Siemion, M; Ciborowski, M; Kretowski, A; Musial, W J; Kaminski, K A

    2016-09-15

    Heart failure (HF) is a complex syndrome representing a final stage of various cardiovascular diseases. Despite significant improvement in the diagnosis and treatment (e.g. ACE-inhibitors, β-blockers, aldosterone antagonists, cardiac resynchronization therapy) of the disease, prognosis of optimally treated patients remains very serious and HF mortality is still unacceptably high. Therefore there is a strong need for further exploration of novel analytical methods, predictive and prognostic biomarkers and more personalized treatment. The metabolism of the failing heart being significantly impaired from its baseline state may be a future target not only for biomarker discovery but also for the pharmacologic intervention. However, an assessment of a particular, isolated metabolite or protein cannot be fully informative and makes a correct interpretation difficult. On the other hand, metabolites profile analysis may greatly assist investigator in an interpretation of the altered pathway dynamics, especially when combined with other lines of evidence (e.g. metabolites from the same pathway, transcriptomics, proteomics). Despite many prior studies on metabolism, the knowledge of peripheral and cardiac pathophysiological mechanisms responsible for the metabolic imbalance and progression of the disease is still insufficient. Metabolomics enabling comprehensive characterization of low molecular weight metabolites (e.g. lipids, sugars, organic acids, amino acids) that reflects the complete metabolic phenotype seems to be the key for further potential improvement in HF treatment (diet-based or biochemical-based). Will this -omics technique one day open a door to easy patients identification before they have a heart failure onset or its decompensation? Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Graft failure following bone marrow transplantation for severe aplastic anemia risk factors and treatment results

    NARCIS (Netherlands)

    Champlin, R.E.; Horowitz, M.M.; Bekkum, D.W. van; Camitta, B.M. Elfenbein, G.E.; Gale, R.P.; Gluckman, E.; Good, R.A.; Rimm, A.A. Rozman, C.; Speck, B. Bortin, M.M

    1989-01-01

    Graft failure was analyzed in 625 patients receiving allogeneic bone marrow transplants from HLA-identical sibling donors as treatment for severe aplastic anemia. Sixty-eight (11%) had no or only transient engraftment. Second bone marrow transplants were successful in achieving extended survival in

  7. In vivo antimalarial activity of extracts of Tanzanian medicinal plants used for the treatment of malaria.

    Science.gov (United States)

    Nondo, Ramadhani S O; Erasto, Paul; Moshi, Mainen J; Zacharia, Abdallah; Masimba, Pax J; Kidukuli, Abdul W

    2016-01-01

    Plants used in traditional medicine have been the source of a number of currently used antimalarial medicines and continue to be a promising resource for the discovery of new classes of antimalarial compounds. The aim of this study was to evaluate in vivo antimalarial activity of four plants; Erythrina schliebenii Harms, Holarrhena pubescens Buch-Ham, Phyllanthus nummulariifolius Poir, and Caesalpinia bonducella (L.) Flem used for treatment of malaria in Tanzania. In vivo antimalarial activity was assessed using the 4-day suppressive antimalarial assay. Mice were infected by injection via tail vein with 2 × 10(7) erythrocytes infected with Plasmodium berghei ANKA. Extracts were administered orally, once daily, for a total of four daily doses from the day of infection. Chloroquine (10 mg/kg/day) and solvent (5 mL/kg/day) were used as positive and negative controls, respectively. The extracts of C. bonducella, E. schliebenii, H. pubescens, and P. nummulariifolius exhibited dose-dependent suppression of parasite growth in vivo in mice, with the highest suppression being by C. bonducella extract. While each of the plant extracts has potential to yield useful antimalarial compounds, the dichloromethane root extract of C. bonducella seems to be the most promising for isolation of active antimalarial compound(s). In vivo antimalarial activity presented in this study supports traditional uses of C. bonducella roots, E. schliebenii stem barks, H. pubescens roots, and P. nummulariifolius for treatment of malaria.

  8. In vivo antimalarial activity of extracts of Tanzanian medicinal plants used for the treatment of malaria

    Directory of Open Access Journals (Sweden)

    Ramadhani SO Nondo

    2016-01-01

    Full Text Available Plants used in traditional medicine have been the source of a number of currently used antimalarial medicines and continue to be a promising resource for the discovery of new classes of antimalarial compounds. The aim of this study was to evaluate in vivo antimalarial activity of four plants; Erythrina schliebenii Harms, Holarrhena pubescens Buch-Ham, Phyllanthus nummulariifolius Poir, and Caesalpinia bonducella (L. Flem used for treatment of malaria in Tanzania. In vivo antimalarial activity was assessed using the 4-day suppressive antimalarial assay. Mice were infected by injection via tail vein with 2 Χ 10 7 erythrocytes infected with Plasmodium berghei ANKA. Extracts were administered orally, once daily, for a total of four daily doses from the day of infection. Chloroquine (10 mg/kg/day and solvent (5 mL/kg/day were used as positive and negative controls, respectively. The extracts of C. bonducella, E. schliebenii, H. pubescens, and P. nummulariifolius exhibited dose-dependent suppression of parasite growth in vivo in mice, with the highest suppression being by C. bonducella extract. While each of the plant extracts has potential to yield useful antimalarial compounds, the dichloromethane root extract of C. bonducella seems to be the most promising for isolation of active antimalarial compound(s. In vivo antimalarial activity presented in this study supports traditional uses of C. bonducella roots, E. schliebenii stem barks, H. pubescens roots, and P. nummulariifolius for treatment of malaria.

  9. Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis.

    Science.gov (United States)

    Zheng, Sean Lee; Chan, Fiona T; Nabeebaccus, Adam A; Shah, Ajay M; McDonagh, Theresa; Okonko, Darlington O; Ayis, Salma

    2018-03-01

    Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO 2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Recommendations for pacemaker implantation for the treatment of atrial tachyarrhythmias and resynchronisation therapy for heart failure

    Science.gov (United States)

    van Hemel, N.M.; Dijkman, B.; de Voogt, W.G.; Beukema, W.P.; Bosker, H.A.; de Cock, C.C.; Jordaens, L.J.L.M.; van Gelder, I.C.; van Gelder, L.M.; van Mechelen, R.; Ruiter, J.H.; Sedney, M.I.; Slegers, L.C.

    2004-01-01

    Today, new pacing algorithms and stimulation methods for the prevention and interruption of atrial tachyarrhythmias can be applied on patients who need bradycardia pacing for conventional reasons. In addition, biventricular pacing as additive treatment for patients with severe congestive heart failure due to ventricular systolic dysfunction and prolonged intraventricular conduction has shown to improve symptoms and reduce hospital admissions. These new pacing technologies and the optimising of the pacing programmes are complex, expensive and time-consuming. Based on many clinical studies the indications for these devices are beginning to emerge. To support the cardiologist's decision-making and to prevent waste of effort and resources, the 'ad hoc committee' has provided preliminary recommendations for implantable devices to treat atrial tachyarrhythmias and to extend the treatment of congestive heart failure respectively. PMID:25696255

  11. Experimental in vivo and in vitro treatment with a new histone deacetylase inhibitor belinostat inhibits the growth of pancreatic cancer

    International Nuclear Information System (INIS)

    Dovzhanskiy, Dmitriy I; Arnold, Stefanie M; Hackert, Thilo; Oehme, Ina; Witt, Olaf; Felix, Klaus; Giese, Nathalia; Werner, Jens

    2012-01-01

    Treatment options for pancreatic ductal adenocarcinoma (PDAC) are limited. Histone deacetylase inhibitors are a new and promising drug family with strong anticancer activity. The aim of this study was to examine the efficacy of in vitro and in vivo treatment with the novel pan-HDAC inhibitor belinostat on the growth of human PDAC cells. The proliferation of tumour cell lines (T3M4, AsPC-1 and Panc-1) was determined using an MTT assay. Apoptosis was analysed using flow cytometry. Furthermore, p21 Cip1/Waf1 and acetylated histone H4 (acH4) expression were confirmed by immunoblot analysis. The in vivo effect of belinostat was studied in a chimeric mouse model. Antitumoural activity was assessed by immunohistochemistry for Ki-67. Treatment with belinostat resulted in significant in vitro and in vivo growth inhibition of PDAC cells. This was associated with a dose-dependent induction of tumour cell apoptosis. The apoptotic effect of gemcitabine was further enhanced by belinostat. Moreover, treatment with belinostat increased expression of the cell cycle regulator p21 Cip1/Waf1 in Panc-1, and of acH4 in all cell lines tested. The reductions in xenograft tumour volumes were associated with inhibition of cell proliferation. Experimental treatment of human PDAC cells with belinostat is effective in vitro and in vivo and may enhance the efficacy of gemcitabine. A consecutive study of belinostat in pancreatic cancer patients alone, and in combination with gemcitabine, could further clarify these effects in the clinical setting

  12. Factors associated with anti-retroviral treatment failure among HIV ...

    African Journals Online (AJOL)

    The odds of ART failure were 1.09 times higher for those with poor knowledge about the purpose of ART drugs (ART Drugs are to Cure HIV AIDS). The odds of ART failure were 1.183 times higher for those with poor attitude (ART is a waste of Time). The odds of ART failure were 1.468 times higher for those with poor ...

  13. Clinical and economic aspects of the use of nebivolol in the treatment of elderly patients with heart failure

    Directory of Open Access Journals (Sweden)

    Donatella Del Sindaco

    2010-12-01

    Full Text Available Donatella Del Sindaco1, Maria Denitza Tinti2, Luca Monzo2, Giovanni Pulignano2,1Heart Failure Unit, Division of Cardiology, INRCA Institute of Care and Research for Elderly, Rome, Italy; 2Heart Failure Clinic, Division of Cardiology/CCU, San Camillo Hospital, Rome, ItalyAbstract: Heart failure is a common and disabling condition with morbidity and mortality that increase dramatically with advancing age. Large observational studies, retrospective subgroup analyses and meta-analyses of clinical trials in systolic heart failure, and recently published randomized studies have provided data supporting the use of beta-blockers as a baseline therapy in heart failure in the elderly. Despite the available evidence about beta-blockers, this therapy is still less frequently used in elderly compared to younger patients. Nebivolol is a third-generation cardioselective beta-blocker with L-arginine/nitric oxide-induced vasodilatory properties, approved in Europe and several other countries for the treatment of essential hypertension, and in Europe for the treatment of stable, mild, or moderate chronic heart failure, in addition to standard therapies in elderly patients aged 70 years old or older. The effects of nebivolol on left ventricular function in elderly patients with chronic heart failure (ENECA and the study of effects of nebivolol intervention on outcomes and rehospitalization in seniors with heart failure (SENIORS have been specifically aimed to assess the efficacy of beta-blockade in elderly heart failure patients. The results of these two trials demonstrate that nebivolol is well tolerated and effective in reducing mortality and morbidity in older patients, and that the beneficial clinical effect is present also in patients with mildly reduced ejection fraction. Moreover, nebivolol appears to be significantly cost-effective when prescribed in these patients. However, further targeted studies are needed to better define the efficacy as well as

  14. Biochemical failure as single abnormality in patients with prostate cancer following radical treatment with external radiotherapy: follow-up without immediate treatment

    Directory of Open Access Journals (Sweden)

    Sergio L. Faria

    2004-08-01

    Full Text Available INTRODUCTION: Biochemical failure has been defined as 3 consecutive increases in PSA following curative treatment of prostate cancer. The appropriate management in such cases is controversial. The most usual treatment has been early introduction of hormones. Such patients will live for many years and hormone therapy causes important secondary effects and increases costs. The guideline in our Department of Radiotherapy has been to follow up, with no initial therapy, cases with low PSA and short PSA doubling time. The present study reports this experience. MATERIALS AND METHODS: 528 patients with localized prostate cancer were treated by radical approach between 1992 and 1999, with external radiotherapy, with or without adjuvant hormone therapy. After a median follow-up of 77 months, there were 207 (39% cases with biochemical failure, 78 of which were followed without therapy after the identification of biochemical failure. All of them were asymptomatic patients and had negative radiographic examinations or did not have imaging exams requested since they presented a favorable outcome. The follow-up included at least 2 annual visits with physical examination and PSA. RESULTS: Of the 78 patients with biochemical failure followed without initial therapy, 7 died from other causes than prostate cancer and the remaining 71 cases were alive and asymptomatic in the last follow-up. Prognostic factors previous to radiotherapy such as stage and Gleason score were not considered when deciding for follow-up without initial therapy in these cases. The most significant aspects considered for this decision were low PSA value (median PSA on the last visit for the 78 cases was only 3.9 ng/mL and a slow PSA doubling time (in the present experience the median PSA doubling time was 22.5 months. CONCLUSION: There seems to be space for expectant management, without initial hormone therapy, in patients with prostate cancer who present biochemical failure and are

  15. Vitamin D and Heart Failure.

    Science.gov (United States)

    Marshall Brinkley, D; Ali, Omair M; Zalawadiya, Sandip K; Wang, Thomas J

    2017-10-01

    Vitamin D is principally known for its role in calcium homeostasis, but preclinical studies implicate multiple pathways through which vitamin D may affect cardiovascular function and influence risk for heart failure. Many adults with cardiovascular disease have low vitamin D status, making it a potential therapeutic target. We review the rationale and potential role of vitamin D supplementation in the prevention and treatment of chronic heart failure. Substantial observational evidence has associated low vitamin D status with the risk of heart failure, ventricular remodeling, and clinical outcomes in heart failure, including mortality. However, trials assessing the influence of vitamin D supplementation on surrogate markers and clinical outcomes in heart failure have generally been small and inconclusive. There are insufficient data to recommend routine assessment or supplementation of vitamin D for the prevention or treatment of chronic heart failure. Prospective trials powered for clinical outcomes are warranted.

  16. In vivo dosimetry with semiconductor and thermoluminescent detectors applied to head and neck cancer treatment; Dosimetria in vivo com uso de detectores semicondutores e termoluminescentes aplicada ao tratamento de cancer de cabeca e pescoco

    Energy Technology Data Exchange (ETDEWEB)

    Viegas, Claudio Castelo Branco

    2003-03-15

    In vivo dosimetry in radiotherapy, i. e, the assessment of the doses received by patients during their treatments, permits a verification of the therapy quality. A routine of in vivo dosimetry is, undoubtedly, a direct benefit for the patient. Unfortunately, in Brazil and in Latin America this procedure is still a privilege for only a few patients. This routine is of common application only in developed countries. The aim of this work is to show the viability and implementation of a routine in vivo dosimetry, using diodes semiconductors and thermoluminescent dosimeters (TLD), at the radiotherapy section of the National Institute of Cancer in Brazil, in the case of head and neck cancer treatment. In order to reach that aim, the characteristics of the response of diodes ISORAD-p and LiF:Mg;Ti (TLD-100) thermoluminescent detectors in powder form were determined. The performance of those detectors for in vivo dosimetry was tested using an RANDO Alderson anthropomorfic phantom and, once their adequacy proved for the kind of measurements proposed, they were used for dose assessment in the case of tumour treatments in the head and neck regions, for Cobalt-60 irradiations. (author)

  17. Application of mobile blood purification system in the treatment of acute renal failure dog model in the field environment

    Directory of Open Access Journals (Sweden)

    Zhi-min ZHANG

    2014-01-01

    Full Text Available Objective To evaluate the stability, safety and efficacy of mobile blood purification system in the treatment of acute renal failure dog model in the field environment. Methods The acute renal failure model was established in 4 dogs by bilateral nephrectomy, which was thereafter treated with the mobile blood purification system. The evaluation of functional index of the mobile blood purification system was performed after a short-time (2 hours and conventional (4 hours dialysis treatment. Results The mobile blood purification system ran stably in the field environment at a blood flow of 150-180ml/min, a dialysate velocity of 2000ml/h, a replacement fluid velocity of 2000ml/h, and ultrafiltration rate of 100-200ml/h. All the functions of alarming system worked well, including static upper limit alarm of ultrafiltration pressure (>100 mmHg, upper limit alarm of ambulatory arterial pressure (>400mmHg, upper limit alarm of ambulatory venous pressure (>400mmHg, bubble alarm of vascular access, bubble alarm during the infusion of solutions, pressure alarm at the substitution pump segment and blood leaking alarm. The vital signs of the 4 dogs with acute renal failure kept stable during the treatment. After the treatment, a remarkable decrease was seen in the levels of serum urea nitrogen, creatinine and serum potassium (P0.05. Conclusions The mobile blood purification system runs normally even in a field environment. It is a flexible and portable device with a great performance in safety and stability in the treatment of acute renal failure. DOI: 10.11855/j.issn.0577-7402.2013.12.15

  18. Bisoprolol for congestive heart failure

    DEFF Research Database (Denmark)

    Rosenberg, J.; Gustafsson, F.

    2008-01-01

    Background: beta-Blockers are a cornerstone in the treatment of systolic heart failure treatment, but not all beta-blockers are effective or in this setting. Objective: To define the role of bisoprolol, a highly selective beta(1)-antagonist in congestive heart failure due to systolic dysfunction....... Methods: Using the keywords 'bisoprolol' and 'heart failure' PubMed and BIOSIS databases were searched for information regarding pharmacology and relevant randomised clinical trials. Supplementary publications were acquired by scrutinising reference lists of relevant papers. Additional information...... was obtained from the FDA website. Conclusion: Bisoprolol is an effective and well-tolerated first-line beta-blocker for patients with systolic heart failure. The knowledge is primarily based on study patients with moderate-to-severe heart failure from the three CIBIS trials Udgivelsesdato: 2008/2...

  19. Clinical Implications of Measuring Drug and Anti-Drug Antibodies by Different Assays When Optimizing Infliximab Treatment Failure in Crohn's Disease

    DEFF Research Database (Denmark)

    Steenholdt, Casper; Bendtzen, Klaus; Brynskov, Jørn

    2014-01-01

    OBJECTIVES: Cost-effective guidance of therapeutic strategy in Crohn's disease patients with secondary infliximab (IFX) treatment failure may be achieved by serum IFX and anti-IFX antibody (Ab) measurements by radioimmunoassay (RIA). This study investigated implications of using other techniques...... on classification of underlying mechanism for treatment failure in most cases (79-94%). The majority (74-88%) failed IFX owing to pharmacodynamic problems, or had noninflammatory pathophysiology for symptoms resembling relapse. Applied threshold for therapeutic vs. subtherapeutic IFX level influenced...

  20. Levosimendan treatment of severe acute congestive heart failure refractory to dobutamine/milrinone in children

    Directory of Open Access Journals (Sweden)

    Prijić Sergej

    2011-01-01

    Full Text Available Introduction. Levosimendan is a novel positive inotropic agent which, improves myocardial contractility through its calcium-sensitizing action, without causing an increase in myocardial oxygen demand. Also, by opening ATP-sensitive potassium channels, it causes vasodilatation with the reduction in both afterload and preload. Because of the long halflife, its effects last for up 7 to 9 days after 24-hour infusion. Case report. We presented three patients 2, 15 and 17 years old. All the patients had severe acute deterioration of the previously diagnosed chronic heart failure (dilatative cardiomyopathy; univentricular heart with bidirectional Glenn anastomosis and restrictive bulboventricular foramen; bacterial endocarditis on artificial aortic valve with severe stenosis and regurgitation. Signs and symptoms of severe heart failure, cardiomegaly (cardio-thoracic index 0.65 and left ventricular dilatation (end-diastolic diameter z-score 2.6; 4.1 and 4.0 were confirmed on admission. Also, myocardial contractility was poor with ejection fraction (EF - 27%, 25%, 35%, fractional shortening (FS - 13%, 11%, 15% and stroke volume (SV - 40, 60, 72 mL/m2. The treatment with standard intravenous inotropic agents resulted in no improvement but in clinical deterioration. Thus, standard intravenous inotropic support was stopped and levosimendan treatment was introduced. All the patients received a continuous 24-h infusion 0.1 μg/kg/min of levosimendan. In a single patient an initial loading dose of 11 μg/kg over 10 min was administrated, too. Levosimendan treatment resulted in both clinical and echocardiography improvement with the improved EF (42%, 34%, 44%, FS (21%, 16%, 22% and SV (59, 82, 93 mL/m2. Hemodynamic improvement was registered too, with the reduction in heart rate in all the treated patients from 134-138 bpm before, to less than 120 bpm after the treatment. These parameters were followed by the normalization of lactate levels. Nevertheless, left

  1. Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship.

    Science.gov (United States)

    Erselcan, Taner; Sungu, Selma; Ozdemir, Semra; Turgut, Bulent; Dogan, Derya; Ozdemir, Ozturk

    2004-05-01

    Although it is well known that radiation induces chromosomal aberrations, there is a lack of information on the in vivo dose-effect relationship in patients receiving iodine-131 treatment, and the results of previous studies are controversial. In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of (131)I (259-3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean+/-SD) were 3.19+/-0.93, 10.83+/-1.72 and 5.75+/-2.06, respectively, in the whole group, and these values differed significantly from each other ( Pdisappearance of damaged lymphocytes from the peripheral circulation in a dose-dependent manner following (131)I treatment. Further studies are therefore needed to clarify the effect of the negative beta value on the biological dosimetry approach in continuous internal low LET radiation, as in the case of (131)I treatment.

  2. Association of the Endobiont Double-Stranded RNA Virus LRV1 With Treatment Failure for Human Leishmaniasis Caused by Leishmania braziliensis in Peru and Bolivia.

    Science.gov (United States)

    Adaui, Vanessa; Lye, Lon-Fye; Akopyants, Natalia S; Zimic, Mirko; Llanos-Cuentas, Alejandro; Garcia, Lineth; Maes, Ilse; De Doncker, Simonne; Dobson, Deborah E; Arevalo, Jorge; Dujardin, Jean-Claude; Beverley, Stephen M

    2016-01-01

    Cutaneous and mucosal leishmaniasis, caused in South America by Leishmania braziliensis, is difficult to cure by chemotherapy (primarily pentavalent antimonials [Sb(V)]). Treatment failure does not correlate well with resistance in vitro, and the factors responsible for treatment failure in patients are not well understood. Many isolates of L. braziliensis (>25%) contain a double-stranded RNA virus named Leishmaniavirus 1 (LRV1), which has also been reported in Leishmania guyanensis, for which an association with increased pathology, metastasis, and parasite replication was found in murine models. Here we probed the relationship of LRV1 to drug treatment success and disease in 97 L. braziliensis-infected patients from Peru and Bolivia. In vitro cultures were established, parasites were typed as L. braziliensis, and the presence of LRV1 was determined by reverse transcription-polymerase chain reaction, followed by sequence analysis. LRV1 was associated significantly with an increased risk of treatment failure (odds ratio, 3.99; P = .04). There was no significant association with intrinsic Sb(V) resistance among parasites, suggesting that treatment failure arises from LRV1-mediated effects on host metabolism and/or parasite survival. The association of LRV1 with clinical drug treatment failure could serve to guide more-effective treatment of tegumentary disease caused by L. braziliensis. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  3. Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia

    Directory of Open Access Journals (Sweden)

    Wongsrichanalai Chansuda

    2009-01-01

    Full Text Available Abstract Background The combination of artesunate and mefloquine was introduced as the national first-line treatment for Plasmodium falciparum malaria in Cambodia in 2000. However, recent clinical trials performed at the Thai-Cambodian border have pointed to the declining efficacy of both artesunate-mefloquine and artemether-lumefantrine. Since pfmdr1 modulates susceptibility to mefloquine and artemisinin derivatives, the aim of this study was to assess the link between pfmdr1 copy number, in vitro susceptibility to individual drugs and treatment failure to combination therapy. Methods Blood samples were collected from P. falciparum-infected patients enrolled in two in vivo efficacy studies in north-western Cambodia: 135 patients were treated with artemether-lumefantrine (AL group in Sampovloun in 2002 and 2003, and 140 patients with artesunate-mefloquine (AM group in Sampovloun and Veal Veng in 2003 and 2004. At enrollment, the in vitro IC50 was tested and the strains were genotyped for pfmdr1 copy number by real-time PCR. Results The pfmdr1 copy number was analysed for 115 isolates in the AM group, and for 109 isolates in the AL group. Parasites with increased pfmdr1 copy number had significantly reduced in vitro susceptibility to mefloquine, lumefantrine and artesunate. There was no association between pfmdr1 polymorphisms and in vitro susceptibilities. In the patients treated with AM, the mean pfmdr1copy number was lower in subjects with adequate clinical and parasitological response compared to those who experienced late treatment failure (n = 112, p p = 0.364. The presence of three or more copies of pfmdr1 were associated with recrudescence in artesunate-mefloquine treated patients (hazard ratio (HR = 7.80 [95%CI: 2.09–29.10], N = 115, p = 0.002 but not with recrudescence in artemether-lumefantrine treated patients (HR = 1.03 [95%CI: 0.24–4.44], N = 109, p = 0.969. Conclusion This study shows that pfmdr1 copy number is a molecular

  4. A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy and Heart Failure

    DEFF Research Database (Denmark)

    Aubdool, Aisah A; Thakore, Pratish; Argunhan, Fulye

    2017-01-01

    cardiovascular disease in two distinct murine models of hypertension and heart failure in vivoMethods -The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin using a CGRP receptor antagonist. The effect of the αAnalogue on Angiotensin II (AngII)-induced hypertension......, Western blot and histology. Results -The AngII-induced hypertension was attenuated by co-treatment with the αAnalogue (50nmol/kg/day, s.c., at a dose selected for lack of long term hypotensive effects at baseline). The αAnalogue protected against vascular, renal and cardiac dysfunction, characterised...... failure. It preserved heart function, assessed by echocardiography, whilst protecting against adverse cardiac remodelling and apoptosis. Moreover, treatment with the αAnalogue was well-tolerated with neither signs of desensitisation nor behavioural changes. Conclusions -These findings, in two distinct...

  5. A method for evaluating treatment quality using in vivo EPID dosimetry and statistical process control in radiation therapy.

    Science.gov (United States)

    Fuangrod, Todsaporn; Greer, Peter B; Simpson, John; Zwan, Benjamin J; Middleton, Richard H

    2017-03-13

    Purpose Due to increasing complexity, modern radiotherapy techniques require comprehensive quality assurance (QA) programmes, that to date generally focus on the pre-treatment stage. The purpose of this paper is to provide a method for an individual patient treatment QA evaluation and identification of a "quality gap" for continuous quality improvement. Design/methodology/approach A statistical process control (SPC) was applied to evaluate treatment delivery using in vivo electronic portal imaging device (EPID) dosimetry. A moving range control chart was constructed to monitor the individual patient treatment performance based on a control limit generated from initial data of 90 intensity-modulated radiotherapy (IMRT) and ten volumetric-modulated arc therapy (VMAT) patient deliveries. A process capability index was used to evaluate the continuing treatment quality based on three quality classes: treatment type-specific, treatment linac-specific, and body site-specific. Findings The determined control limits were 62.5 and 70.0 per cent of the χ pass-rate for IMRT and VMAT deliveries, respectively. In total, 14 patients were selected for a pilot study the results of which showed that about 1 per cent of all treatments contained errors relating to unexpected anatomical changes between treatment fractions. Both rectum and pelvis cancer treatments demonstrated process capability indices were less than 1, indicating the potential for quality improvement and hence may benefit from further assessment. Research limitations/implications The study relied on the application of in vivo EPID dosimetry for patients treated at the specific centre. Sampling patients for generating the control limits were limited to 100 patients. Whilst the quantitative results are specific to the clinical techniques and equipment used, the described method is generally applicable to IMRT and VMAT treatment QA. Whilst more work is required to determine the level of clinical significance, the

  6. Deferred modification of antiretroviral regimen following documented treatment failure in Asia: results from the TREAT Asia HIV Observational Database (TAHOD)

    Science.gov (United States)

    Zhou, J; Li, PCK; Kumarasamy, N; Boyd, M; Chen, YMA; Sirisanthana, T; Sungkanuparph, S; Oka, S; Tau, G; Phanuphak, P; Saphonn, V; Zhang, FJ; Omar, SFS; Lee, CKC; Ditangco, R; Merati, TP; Lim, PL; Choi, JY; Law, MG; Pujari, S

    2010-01-01

    Objective The aim of the study was to examine the rates and predictors of treatment modification following combination antiretroviral therapy (cART) failure in Asian patients with HIV enrolled in the TREAT Asia HIV Observational Database (TAHOD). Methods Treatment failure (immunological, virological and clinical) was defined by World Health Organization criteria. Countries were categorized as high or low income by World Bank criteria. Results Among 2446 patients who initiated cART, 447 were documented to have developed treatment failure over 5697 person-years (7.8 per 100 person-years). A total of 253 patients changed at least one drug after failure (51.6 per 100 person-years). There was no difference between patients from high- and low-income countries [adjusted hazard ratio (HR) 1.02; P = 0.891]. Advanced disease stage [Centers for Disease Control and Prevention (CDC) category C vs. A; adjusted HR 1.38, P = 0.040], a lower CD4 count (≥ 51 cells/μL vs. ≤ 50 cells/μL; adjusted HR 0.61, P = 0.022) and a higher HIV viral load (≥ 400 HIV-1 RNA copies/mL vs. failure. Compared with patients from low-income countries, patients from high-income countries were more likely to change two or more drugs (67% vs. 49%; P = 0.009) and to change to a protease-inhibitor-containing regimen (48% vs. 16%; Pfailure. This deferred modification is likely to have negative implications for accumulation of drug resistance and response to second-line treatment. There is a need to scale up the availability of second-line regimens and virological monitoring in this region. PMID:19601993

  7. In vivo neutron activation analysis: body composition studies in health and disease

    International Nuclear Information System (INIS)

    Ellis, K.J.; Cohn, S.H.

    1984-01-01

    In vivo analysis of body elements by neutron activation is an important tool in medical research. It has provided a direct quantitative measure of body composition of human beings in vivo. Basic physiological differences related to age, sex, race, and body size have been assessed by this noninvasive technique. The diagnosis and management of patients with various metabolic disorders and diseases has also been demonstrated. Two major facilities at Brookhaven are being utilized exclusively for in vivo neutron activation analysis (IVNAA) of calcium, phosphorus, sodium, chlorine, nitrogen, hydrogen, and potassium. These elements serve as the basis for a four compartment model of body composition: protein, water, mineral ash, and fat. Variations in these compartments are demonstrated in clinical research programs investigating obesity, anorexia, cancer, renal failure, osteoporosis, and normal aging. IVNAA continues to provide a unique approach to the evaluation of clinical diagnosis, efficacy of therapeutic regimens, and monitoring of the aging process. Classical balance studies usually require the patient to be admitted to a hospital for extended periods of confinement. IVNAA, however, allows for clinical management of the patient on an out-patient basis, an important aspect for treatment of chronic diseases. 25 references, 3 figures, 5 tables

  8. In vivo neutron activation analysis: body composition studies in health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, K.J.; Cohn, S.H.

    1984-01-01

    In vivo analysis of body elements by neutron activation is an important tool in medical research. It has provided a direct quantitative measure of body composition of human beings in vivo. Basic physiological differences related to age, sex, race, and body size have been assessed by this noninvasive technique. The diagnosis and management of patients with various metabolic disorders and diseases has also been demonstrated. Two major facilities at Brookhaven are being utilized exclusively for in vivo neutron activation analysis (IVNAA) of calcium, phosphorus, sodium, chlorine, nitrogen, hydrogen, and potassium. These elements serve as the basis for a four compartment model of body composition: protein, water, mineral ash, and fat. Variations in these compartments are demonstrated in clinical research programs investigating obesity, anorexia, cancer, renal failure, osteoporosis, and normal aging. IVNAA continues to provide a unique approach to the evaluation of clinical diagnosis, efficacy of therapeutic regimens, and monitoring of the aging process. Classical balance studies usually require the patient to be admitted to a hospital for extended periods of confinement. IVNAA, however, allows for clinical management of the patient on an out-patient basis, an important aspect for treatment of chronic diseases. 25 references, 3 figures, 5 tables.

  9. The D543N polymorphism of the SLC11A1/NRAMP1 gene is associated with treatment failure in male patients with pulmonary tuberculosis.

    Science.gov (United States)

    Salinas-Delgado, Yvain; Galaviz-Hernández, Carlos; Toral, René García; Ávila Rejón, Carmen A; Reyes-Lopez, Miguel A; Martínez, Antonio Rojas; Martínez-Aguilar, Gerardo; Sosa-Macías, Martha

    2015-09-01

    Polymorphisms in SLC11A1/NRAMP1 have shown an important association with susceptibility to tuberculosis and progression to active disease. However, whether there is an association of these polymorphisms with treatment failure is unknown. The aim of this study was to determine the association of SLC11A1 polymorphisms with treatment failure in Mexican subjects with pulmonary tuberculosis. Thirty-three subjects with treatment failure were paired by age and body mass index with 33 patients who successfully completed treatment and were considered cured. We assessed the polymorphisms of SLC11A1 in the regions of D543N and INT4 via polymerase chain reaction real-time TaqMan® single nucleotide polymorphism (SNP) genotyping. We found that D543N (G/A genotype) was associated with treatment failure in patients with pulmonary tuberculosis [odds ratio (OR) 11.61, 95% confidence interval (CI) 3.66-36.78]. When adjusted by gender, this association remained significant in males (OR 11.09, 95% CI 3.46-35.51). In our male population, the presence of the D543N polymorphism of SLC11A1 is a risk factor for treatment failure. This finding should be confirmed in other populations.

  10. Increased in vivo mitochondrial oxygenation with right ventricular failure induced by pulmonary arterial hypertension: Mitochondrial inhibition as driver of cardiac failure?

    NARCIS (Netherlands)

    G. Balestra (Gianmarco); E.G. Mik (Egbert); O. Eerbeek (Otto); P. Specht (Patricia); W.J. van der Laarse (Willem J.); C.J. Zuurbier (Coert J.)

    2015-01-01

    textabstractBackground: The leading cause of mortality due to pulmonary arterial hypertension (PAH) is failure of the cardiac right ventricle. It has long been hypothesized that during the development of chronic cardiac failure the heart becomes energy deprived, possibly due to shortage of oxygen at

  11. Does less frequent routine monitoring of patients on a stable, fully suppressed cART regimen lead to an increased risk of treatment failure?

    DEFF Research Database (Denmark)

    Reekie, Joanne; Mocroft, Amanda; Sambatakou, Helen

    2008-01-01

    SIDA study who maintained a stable and fully suppressed cART regimen for 1 year were included in the analysis. METHODS: Risk of treatment failure, defined by viral rebound, fall in CD4 cell count, development of new AIDS-defining illness, serious opportunistic infection or death, in the 12 months following...... interval (CI) 0.1-0.5], 2.2% (95% CI 1.6-2.8) and 6.0% (95% CI 5.0-7.0) risk of treatment failure, respectively. Patients who spent more than 80% of their time on cART with fully suppressed viraemia prior to baseline had a 38% reduced risk of treatment failure, hazard ratio 0.62 (95% CI 0.42-0.90, P = 0...

  12. Treatment of anemia with darbepoetin alfa in systolic heart failure

    DEFF Research Database (Denmark)

    Swedberg, Karl; Young, James B; Anand, Inder S

    2013-01-01

    Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia.......Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia....

  13. LOW-MOLECULAR-WEIGHT HEPARIN TREATMENT FAILURE IN PREVENTION OF PROSTHETIC MITRAL VALVE THROMBOSIS

    OpenAIRE

    David Šuran; Vojko Kanič; Tatjana Golob Gulič; Husam Franjo Naji; Robert Lipovec

    2009-01-01

    Background Prosthetic heart valve thrombosis (PHVT) represents a dangerous postoperative complication following prosthetic heart valve replacement. Incidence varies according to different data from 0.5–4 % per year following mitral or aortic valve replacement in spite of adequate oral anticoagulation with coumarins. Case report We are presenting a case of prosthetic mitral valve thrombosis as a result of 6-month lowmolecular-weight heparin (LMWH) (nadroparine) treatment failure. Our pat...

  14. Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme

    International Nuclear Information System (INIS)

    Shields, Lisa BE; Kadner, Robert; Vitaz, Todd W; Spalding, Aaron C

    2013-01-01

    We investigated the pattern of failure in glioblastoma multiforma (GBM) patients treated with concurrent radiation, bevacizumab (BEV), and temozolomide (TMZ). Previous studies demonstrated a predominantly in-field pattern of failure for GBM patients not treated with concurrent BEV. We reviewed the treatment of 23 patients with GBM who received 30 fractions of simultaneous integrated boost IMRT. PTV60 received 2 Gy daily to the tumor bed or residual tumor while PTV54 received 1.8 Gy daily to the surrounding edema. Concurrent TMZ (75 mg/m 2 ) daily and BEV (10 mg/kg every 2 weeks) were given during radiation therapy. One month after RT completion, adjuvant TMZ (150 mg/m 2 × 5 days) and BEV were delivered monthly until progression or 12 months total. With a median follow-up of 12 months, the median disease-free and overall survival were not reached. Four patients discontinued therapy due to toxicity for the following reasons: bone marrow suppression (2), craniotomy wound infection (1), and pulmonary embolus (1). Five patients had grade 2 or 3 hypertension managed by oral medications. Of the 12 patients with tumor recurrence, 7 suffered distant failure with either subependymal (5/12; 41%) or deep white matter (2/12; 17%) spread detected on T2 FLAIR sequences. Five of 12 patients (41%) with a recurrence demonstrated evidence of GAD enhancement. The patterns of failure did not correlate with extent of resection or number of adjuvant cycles. Treatment of GBM patients with concurrent radiation, BEV, and TMZ was well tolerated in the current study. The majority of patients experienced an out-of-field pattern of failure with radiation, BEV, and TMZ which has not been previously reported. Further investigation is warranted to determine whether BEV alters the underlying tumor biology to improve survival. These data may indicate that the currently used clinical target volume thought to represent microscopic disease for radiation may not be appropriate in combination with TMZ

  15. Application of Failure Mode and Effects Analysis to Intraoperative Radiation Therapy Using Mobile Electron Linear Accelerators

    International Nuclear Information System (INIS)

    Ciocca, Mario; Cantone, Marie-Claire; Veronese, Ivan; Cattani, Federica; Pedroli, Guido; Molinelli, Silvia; Vitolo, Viviana; Orecchia, Roberto

    2012-01-01

    Purpose: Failure mode and effects analysis (FMEA) represents a prospective approach for risk assessment. A multidisciplinary working group of the Italian Association for Medical Physics applied FMEA to electron beam intraoperative radiation therapy (IORT) delivered using mobile linear accelerators, aiming at preventing accidental exposures to the patient. Methods and Materials: FMEA was applied to the IORT process, for the stages of the treatment delivery and verification, and consisted of three steps: 1) identification of the involved subprocesses; 2) identification and ranking of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system, based on the product of three parameters (severity, frequency of occurrence and detectability, each ranging from 1 to 10); 3) identification of additional safety measures to be proposed for process quality and safety improvement. RPN upper threshold for little concern of risk was set at 125. Results: Twenty-four subprocesses were identified. Ten potential failure modes were found and scored, in terms of RPN, in the range of 42–216. The most critical failure modes consisted of internal shield misalignment, wrong Monitor Unit calculation and incorrect data entry at treatment console. Potential causes of failure included shield displacement, human errors, such as underestimation of CTV extension, mainly because of lack of adequate training and time pressures, failure in the communication between operators, and machine malfunctioning. The main effects of failure were represented by CTV underdose, wrong dose distribution and/or delivery, unintended normal tissue irradiation. As additional safety measures, the utilization of a dedicated staff for IORT, double-checking of MU calculation and data entry and finally implementation of in vivo dosimetry were suggested. Conclusions: FMEA appeared as a useful tool for prospective evaluation of patient safety in radiotherapy

  16. Non small-cell lung cancer and treatment options after tyrosine kinase inhibitors failure in the first line

    International Nuclear Information System (INIS)

    Chowaniecova, G.

    2014-01-01

    Introduction: Advanced non-small cell lung cancer with present epidermal growth factor receptor (EGFR) sensitising mutation is standardly treated with tyrosine kinase inhibitors (TKI). During treatment a resistance to TKI develops, disease progresses. We differ primary and secondary resistance. The most effective treatment after TKI failure is not definitively proven. Standard chemotherapy is usually introduced, eventually it is possible to use other TKI in the next lines. Case: The author presents a case of 60-year old patient with lung adenocarcinoma with EGFR sensitising mutation, where primary resistance to TKI was observed. Chemotherapy after progression was introduced. Planned therapy with afatnib was not carried out due to deterioration of patient´s condition. Conclusion: Presented case of EGFR mutation-positive patient represents an example of not very frequent primary resistance to TKI. Mechanisms of primary resistance are not well understood. Treatment after first line TKI failure in non-small cell lung cancer with EGFR mutation represents a challenge for medical research. (author)

  17. Preliminary investigation of hybrid bioartificial liver support system in treatment of HBV-related acute-on-chronic liver failure

    Directory of Open Access Journals (Sweden)

    YOU Shaoli

    2013-09-01

    Full Text Available ObjectiveTo construct a hybrid bioartificial liver support system and to investigate its safety and efficacy in patients with hepatitis B virus (HBV-related acute-on-chronic liver failure (ACLF. MethodsA hollow fiber bioreactor was constructed using cultured HepG2 cells transfected with human augmenter of liver regeneration gene. Patients with HBV-related ACLF who were hospitalized in our hospital from May 2009 to August 2011 were randomly divided into treatment group (n=10 and control group (n=10. The treatment group was treated using the hybrid bioartificial liver support system, while the control group was treated with conventional plasma exchange. Comparison of means between the two groups was made by independent-samples t test, and comparison of variables before and after treatment was made by paired t test. ResultsOf the 10 patients in treatment group, 7 had improvement in clinical symptoms and were discharged, 1 died of hepatic encephalopathy, 1 died of hepatorenal syndrome, and 1 died of liver failure after discharge. Of the 10 patients in control group, 5 survived, 1 underwent liver transplantation, and 4 died of liver failure. Before treatment, the treatment group and control group had model for end-stage liver disease (MELD scores of 24.26±2.54 and 24.71±2.79, respectively, without significant difference between the two groups (t=1.971, P=0.064. The treatment group had MELD scores of 21.71±2.92, 22.10±4.46, and 19.90±5.43 after 3 days, 1 week, and 4 weeks, respectively, of treatment. At the end of one-year follow-up, the mean serum alpha-fetoprotein levels were 14.24 ng/ml in treatment group and 11.32 ng/ml in control group, and no space-occupying lesions in the liver were found through abdominal ultrasound. ConclusionThe constructed hybrid bioartificial liver support system is effective and safe in the treatment of HBV-related ACLF.

  18. In vivo dosimetry in radiation therapy in Sweden; In vivo-dosimetri inom straalbehandling i Sverige

    Energy Technology Data Exchange (ETDEWEB)

    Eriksson, Jacob; Blomquist, Michael (Norrlands universitetssjukhus, Umeaa (Sweden))

    2010-07-15

    A prerequisite for achieving high radiation safety for patients receiving external beam radiation therapy is that the hospitals have a quality assurance program. The program should include include monitoring of the radiation dose given to the patient. Control measurements are performed both at the system level and at the individual level. Control measurement is normally performed using in vivo dosimetry, e.g. a method to measure the radiation dose at the individual level during the actual radiation treatment time. In vivo dosimetry has proven to be an important tool to detect and prevent serious errors in patient treatment. The purpose of this research project was to identify the extent to which vivo dosimetry is used and the methods available for this at Swedish radiation therapy clinics. The authority also wanted to get an overall picture of how hospitals manage results of in vivo dosimetry, and how clinics control radiation dose when using modern treatment techniques. The report reflects the situation in Swedish radiotherapy clinics 2007. The report shows that all hospitals use some form of in vivo dosimetry. The instruments used are mainly diodes and termoluminiscence dosimeters

  19. Diabetic db/db mice do not develop heart failure upon pressure overload: a longitudinal in vivo PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations.

    Science.gov (United States)

    Abdurrachim, Desiree; Nabben, Miranda; Hoerr, Verena; Kuhlmann, Michael T; Bovenkamp, Philipp; Ciapaite, Jolita; Geraets, Ilvy M E; Coumans, Will; Luiken, Joost J F P; Glatz, Jan F C; Schäfers, Michael; Nicolay, Klaas; Faber, Cornelius; Hermann, Sven; Prompers, Jeanine J

    2017-08-01

    Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. Transverse aortic constriction (TAC) was performed in non-diabetic (db/+) and diabetic (db/db) mice to induce pressure overload. Magnetic resonance imaging, 31P magnetic resonance spectroscopy (MRS), 1H MRS, and 18F-fluorodeoxyglucose-positron emission tomography (PET) were applied to measure cardiac function, energy status, lipid content, and glucose uptake, respectively. In vivo measurements were complemented with ex vivo techniques of high-resolution respirometry, proteomics, and western blotting to elucidate the underlying molecular pathways. In non-diabetic mice, TAC induced progressive cardiac hypertrophy and dysfunction, which correlated with increased protein kinase D-1 (PKD1) phosphorylation and increased glucose uptake. These changes in glucose utilization preceded a reduction in cardiac energy status. At baseline, compared with non-diabetic mice, diabetic mice showed normal cardiac function, higher lipid content and mitochondrial capacity for fatty acid oxidation, and lower PKD1 phosphorylation, glucose uptake, and energetics. Interestingly, TAC affected cardiac function only mildly in diabetic mice, which was accompanied by normalization of phosphorylated PKD1, glucose uptake, and cardiac energy status. The cardiac metabolic adaptations in diabetic mice seem to prevent the heart from failing upon pressure overload, suggesting that restoring the balance between glucose and fatty acid utilization is beneficial for cardiac function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions

  20. [The Predictive Factors of Stent Failure in the Treatment of Malignant Extrinsc Ureteral Obstruction Using Internal Ureteral Stents].

    Science.gov (United States)

    Matsuura, Hiroshi; Arase, Shigeki; Hori, Yasuhide; Tochigi, Hiromi

    2017-12-01

    In this study, we retrospectively reviewed the experiences at our single institute in the treatment of malignant extrinsic ureteral obstruction (MUO) using ureteral stents to investigate the clinical outcomes and the predictive factors of stent failure. In 52 ureters of 38 patients who had radiologically significant hydronephrosis due to MUO, internal ureteral stents (The BARD(R) INLAY(TM) ureteral stent set) were inserted. The median follow-up interval after the initial stent insertion was 124.5 days (4-1,120). Stent failure occurred in 8 ureters (15.4%) of the 7 patients. The median interval from the first stent insertion to stent failure was 88 days (1-468). A Cox regression multivariate analysis showed that the significant predictors of stent failure were bladder invasion. Based on the possibility of stent failure, the adaptation of the internal ureteral stent placement should be considered especially in a patient with MUO combined with bladder invasion.

  1. Virtual reality compared with in vivo exposure in the treatment of social anxiety disorder: a three-arm randomised controlled trial.

    Science.gov (United States)

    Bouchard, Stéphane; Dumoulin, Stéphanie; Robillard, Geneviève; Guitard, Tanya; Klinger, Évelyne; Forget, Hélène; Loranger, Claudie; Roucaut, François Xavier

    2017-04-01

    Background People with social anxiety disorder (SAD) fear social interactions and may be reluctant to seek treatments involving exposure to social situations. Social exposure conducted in virtual reality (VR), embedded in individual cognitive-behavioural therapy (CBT), could be an answer. Aims To show that conducting VR exposure in CBT for SAD is effective and is more practical for therapists than conducting exposure in vivo Method Participants were randomly assigned to either VR exposure ( n = 17), in vivo exposure ( n = 22) or waiting list ( n = 20). Participants in the active arms received individual CBT for 14 weekly sessions and outcome was assessed with questionnaires and a behaviour avoidance test. (Trial registration number ISRCTN99747069) Results Improvements were found on the primary (Liebowitz Social Anxiety Scale) and all five secondary outcome measures in both CBT groups compared with the waiting list. Conducting exposure in VR was more effective at post-treatment than in vivo on the primary outcome measure and on one secondary measure. Improvements were maintained at the 6-month follow-up. VR was significantly more practical for therapists than in vivo exposure. Conclusions Using VR can be advantageous over standard CBT as a potential solution for treatment avoidance and as an efficient, cost-effective and practical medium of exposure. © The Royal College of Psychiatrists 2017.

  2. The frequency of anti-infliximab antibodies in patients with rheumatoid arthritis treated in routine care and the associations with adverse drug reactions and treatment failure

    DEFF Research Database (Denmark)

    Krintel, Sophine B; Grunert, Veit Peter; Hetland, Merete L

    2013-01-01

    To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure.......To investigate the frequency of anti-infliximab antibodies in patients with RA and the associations with adverse drug reactions and treatment failure....

  3. Construction of radiation - induced metastasis model in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Kuk; Jang, Su Jin; Kang, Sung Wook; Kim, Jae Sung; Hwang, Sang Gu; Kang, Joo Hyun [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2011-05-15

    In treatment of cancer, distant metastases are important limiting factor because an estimated 50% of all cancer patients will develop metastases, and the metastases are major causing of cancer treatment failure. Recently a few reports indicated {gamma}-radiation induced an increase of invasiveness of several cancer cells. In this study, we had tried to show the possibility that radiation could also induce metastasis in vivo system. To prove our hypothesis, we constructed primary tumor by using C6-TL transfectant cell line expressing HSV1-tk and firefly luciferase (fLuc), and then {gamma}-radiation was treated to xenografts locally. Treatment of {gamma}-radiation to primary C6-TL xenografts of mice reduced size of xenografts and elongated survival of mice than those of mock control mice. But we also show that {gamma}-radiation treatment was followed by the growth of dormant metastases in various organs including lung and intestine after 2-4 weeks of {gamma}-radiation treatment. When bioluminescence imaging indicated growth of tumor in organs in mice, we sacrificed the mice and repeat acquired bioluminescence imaging after repeatedly. These images presented tumor growth locations exactly in organs. Because metastatic tumor candidates have morphology of foci, biopsies were performed for histological analysis or PCR analysis to confirm metastases. In most foci, histological analysis indicated several features of typical cancer tissue and PCR analysis showed present of fLuc gene in metastases. Detection of fLuc gene in metastases indicated these foci were originated from primary C6-TL xenografts, and the results suggest that {gamma}-radiation could promote metastasis in vivo as well as in vitro system. Although we need to understand changes of intracellular signaling or physiological phenomena of the radiation-induced metastasis yet, these results also imply that {gamma}-radiation treatment only to cancer patients need to pay attention carefully, and development of new

  4. Exercise training restores cardiac protein quality control in heart failure.

    Directory of Open Access Journals (Sweden)

    Juliane C Campos

    Full Text Available Exercise training is a well-known coadjuvant in heart failure treatment; however, the molecular mechanisms underlying its beneficial effects remain elusive. Despite the primary cause, heart failure is often preceded by two distinct phenomena: mitochondria dysfunction and cytosolic protein quality control disruption. The objective of the study was to determine the contribution of exercise training in regulating cardiac mitochondria metabolism and cytosolic protein quality control in a post-myocardial infarction-induced heart failure (MI-HF animal model. Our data demonstrated that isolated cardiac mitochondria from MI-HF rats displayed decreased oxygen consumption, reduced maximum calcium uptake and elevated H₂O₂ release. These changes were accompanied by exacerbated cardiac oxidative stress and proteasomal insufficiency. Declined proteasomal activity contributes to cardiac protein quality control disruption in our MI-HF model. Using cultured neonatal cardiomyocytes, we showed that either antimycin A or H₂O₂ resulted in inactivation of proteasomal peptidase activity, accumulation of oxidized proteins and cell death, recapitulating our in vivo model. Of interest, eight weeks of exercise training improved cardiac function, peak oxygen uptake and exercise tolerance in MI-HF rats. Moreover, exercise training restored mitochondrial oxygen consumption, increased Ca²⁺-induced permeability transition and reduced H₂O₂ release in MI-HF rats. These changes were followed by reduced oxidative stress and better cardiac protein quality control. Taken together, our findings uncover the potential contribution of mitochondrial dysfunction and cytosolic protein quality control disruption to heart failure and highlight the positive effects of exercise training in re-establishing cardiac mitochondrial physiology and protein quality control, reinforcing the importance of this intervention as a non-pharmacological tool for heart failure therapy.

  5. Multimodal Imaging for In Vivo Evaluation of Induced Pluripotent Stem Cells in a Murine Model of Heart Failure.

    Science.gov (United States)

    Rojas, Sebastian V; Meier, Martin; Zweigerdt, Robert; Eckardt, Dominik; Rathert, Christian; Schecker, Natalie; Schmitto, Jan D; Rojas-Hernandez, Sara; Martin, Ulrich; Kutschka, Ingo; Haverich, Axel; Martens, Andreas

    2017-02-01

    Myocardial stem cell therapy in heart failure is strongly dependent on successful cellular transfer, engraftment, and survival. Moreover, massive cell loss directly after intramyocardial injection is commonly observed, generating the need for efficient longitudinal monitoring of transplanted cells in order to develop more efficient transplantation techniques. Therefore, the aim of the present study was to assess viability and cardiac retention of induced pluripotent stem cells after intramyocardial delivery using in vivo bioluminescence analysis (BLI) and magnetic resonance imaging (MRI). Murine induced pluripotent stem cells (iPSCs) were transfected for luciferase reporter gene expression and labeled intracellularly with supraparamagnetic iron oxide particles. Consequently, 5 × 10 5 cells were transplanted intramyocardially following left anterior descending coronary artery ligation in mice. Cardiac iPSCs were detected using BLI and serial T2* sequences by MRI in a 14-day follow-up. Additionally, infarct extension and left ventricular (LV) function were assessed by MRI. Controls received the same surgical procedure without cell injection. MRI sequences showed a strong MRI signal of labeled iPSCs correlating with myocardial late enhancement, demonstrating engraftment in the infarcted area. Mean iPSC volumes were 4.2 ± 0.4 mm 3 at Day 0; 3.1 ± 0.4 mm 3 at Day 7; and 5.1 ± 0.8 mm 3 after 2 weeks. Thoracic BLI radiance decreased directly after injection from 1.0 × 10 6  ± 4.2 × 10 4 (p/s/cm 2 /sr) to 1.0 × 10 5  ± 4.9 × 10 3 (p/s/cm 2 /sr) on Day 1. Afterward, BLI radiance increased to 1.1 × 10 6  ± 4.2 × 10 4 (p/s/cm 2 /sr) 2 weeks after injection. Cardiac graft localization was confirmed by ex vivo BLI analysis and histology. Left ventricular ejection fraction was higher in the iPSC group (30.9 ± 0.9%) compared to infarct controls (24.0 ± 2.1%; P stem cell fate in vivo, enabling cardiac graft localization with

  6. MARS treatment in posthepatectomy liver failure

    NARCIS (Netherlands)

    van de Kerkhove, Maarten-Paul; de Jong, Koert P.; Rijken, Arjen M.; de Pont, Anne-Cornélie J. M.; van Gulik, Thomas M.

    2003-01-01

    Posthepatactomy liver failure (PHLF) is a dramatic complication following extensive liver resection or liver resection in a compromised liver, leading to death in 80% of cases. Molecular Adsorbent Recirculating System (MARS) is able to extract water and protein bound toxins out of the blood in liver

  7. Risk factors for unsuccessful tuberculosis treatment outcome (failure, default and death) in public health institutions, Eastern Ethiopia.

    Science.gov (United States)

    Amante, Tariku Dingeta; Ahemed, Tekabe Abdosh

    2015-01-01

    Unsuccessful TB treatment outcome is a serious public health concern. It is compelling to identify, and deal with factors determining unsuccessful treatment outcome. Therefore, study was aimed to determine pattern of unsuccessful TB treatment outcome and associated factors in eastern Ethiopia. A case control study was used. Cases were records of TB patients registered as defaulter, dead and/or treatment failure where as controls were those cured or treatment complete. Multivariate logistic regression models were used to derive adjusted odds ratios (OR) at 95% CI to examine the relationship between the unsuccessful TB treatment outcome and patients' characteristics. A total of 990 sample size (330 cases and 660 controls) were included. Among cases (n = 330), majority 212(64.2%) were because of death, 100(30.3%) defaulters and 18(5.5%) were treatment failure. Lack of contact person(OR = 1.37; 95% CI 1.14-2.9, P, .024), sputum smear negative treatment category at initiation of treatment (OR = 1.8; 95% CI 1.3-5.5,P, .028), smear positive sputum test result at 2(nd) month after initiation treatment (OR = 14; 95% CI 5.5-36, P,0.001) and HIV positive status (OR = 2.5; 95% CI 1.34-5.7, P, 0.01) were independently associated with increased risk of unsuccessful TB treatment outcome. Death was the major cause of unsuccessful TB treatment outcome. TB patients do not have contact person, sputum smear negative treatment category at initiation of treatment, smear positive on 2(nd) month after treatment initiation and HIV positive were factors significantly associated unsuccessful treatment outcome. TB patients with sputum smear negative treatment category, HIV positive and smear positive on 2(nd) nd month of treatment initiation need strict follow up throughout DOTs period.

  8. Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study

    Directory of Open Access Journals (Sweden)

    Xu J

    2017-10-01

    Full Text Available Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People’s Republic of China Background: Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR-mutant non-small cell lung cancer (NSCLC who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure.Patients and methods: This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally. Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal.Results: Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS was 5.33 months (95% CI, 3.63–7.03 months. Moreover, the objective response rate (ORR was 11.1%, and the disease control rate (DCR was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4% and fatigue (37.0%.Conclusion: Apatinib plus

  9. Analysis of the cause of failure in nonsurgical endodontic treatment by microscopic inspection during endodontic microsurgery.

    Science.gov (United States)

    Song, Minju; Kim, Hyeon-Cheol; Lee, Woocheol; Kim, Euiseong

    2011-11-01

    This study examined the clinical causes of failure and the limitation of a previous endodontic treatment by an inspection of the root apex and resected root surface at 26× magnification during endodontic microsurgery. The data were collected from patients in the Department of Conservative Dentistry at the Dental College, Yonsei University in Seoul, Korea between March 2001 and January 2011. All root-filled cases with symptomatic or asymptomatic apical periodontitis were enrolled in this study. All surgical procedures were performed by using an operating microscope. The surface of the apical root to be resected or the resected root surface after methylene blue staining was examined during the surgical procedure and recorded carefully with 26× magnification to determine the state of the previous endodontic treatment by using an operating microscope. Among the 557 cases with periapical surgery, 493 teeth were included in this study. With the exclusion of unknown cases, the most common possible cause of failure was perceived leakage around the canal filling material (30.4%), followed by a missing canal (19.7%), underfilling (14.2%), anatomical complexity (8.7%), overfilling (3.0%), iatrogenic problems (2.8%), apical calculus (1.8%), and cracks (1.2%). The frequency of possible failure causes differed according to the tooth position (P < .001). An appreciation of the root canal anatomy by using an operating microscope in nonsurgical endodontic treatment can make the prognosis more predictable and favorable. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  10. Treatment failure in a typhoid patient infected with nalidixic acid resistant S. enterica serovar Typhi with reduced susceptibility to Ciprofloxacin: a case report from Cameroon

    Directory of Open Access Journals (Sweden)

    Asonganyi Etienne DN

    2005-06-01

    Full Text Available Abstract Background Fluoroquinolones or third generation cephalosporins are the drugs of choice for the treatment of typhoid fever. Treatment failure with fluoroquinolones has been reported in Asia and Europe. We report a case of ciprofloxacin treatment failure in typhoid fever in Cameroon. Case presentation A 29-year-old female patient with suspected typhoid fever from Kumba, Cameroon, yielded growth of Salmonella enterica serovar Typhi in blood culture. The isolate was resistant to nalidixic acid but sensitive to ciprofloxacin by disc diffusion test. However, the patient did not respond to treatment with ciprofloxacin, although the isolate was apparently susceptible to ciprofloxacin. Conclusion Treatment failure with ciprofloxacin in our case indicates the presence of nalidixic acid resistant S. enterica serovar Typhi (NARST with reduced susceptibility to ciprofloxacin in Cameroon (Central Africa.

  11. Reassessing guidelines for heart failure

    Directory of Open Access Journals (Sweden)

    Helmut Drexler

    2004-03-01

    Full Text Available Significant progress has been made in the last few years in the management of heart failure. In particular several trials have given significant results. It has become apparent that heart failure may be prevented in some patients by treatment of risk factors such as coronary artery disease. Experience with angiotensin-converting enzyme (ACE inhibitors has shown that the survival and symptomatic benefits do last in the long term, and confirm that they are the first-line treatment in heart failure. The results of a number of trials using the angiotensin receptor blockers (ARBs candesartan, valsartan and losartan are presented and discussed. There is also some experience now in the use of candesartan for patients with heart failure and preserved left ventricular systolic function. The COMET trial compared the β-blockers carvedilol and metoprolol tartrate, and suggests that there may be differences in clinical effect between β-blockers. The selective aldosterone receptor blocker eplerenone was evaluated in the EPHESUS trial in post-MI patients with signs of heart failure. Based on these clinical trials, heart failure guidelines are now being updated.

  12. Gut hormones in the treatment of short-bowel syndrome and intestinal failure

    DEFF Research Database (Denmark)

    Jeppesen, Palle B

    2015-01-01

    PURPOSE OF REVIEW: The approval of teduglutide, a recombinant analog of human glucagon-like peptide (GLP) 2, by the US Food and Drug Administration (Gattex) and the European Medicines Agency (Revestive) has illustrated the potential of selected gut hormones as treatments in patients with short......-bowel syndrome and intestinal failure. Gut hormones may improve the structural and functional intestinal adaptation following intestinal resection by decreasing a rapid gastric emptying and hypersecretion, by increasing the intestinal blood flow, and by promoting intestinal growth. This review summarizes......-1 may be less potent. Synergistic effects may be seen by co-treatment with GLP-2. SUMMARY: Gut hormones promote intestinal adaptation and absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. This will aid the intestinal rehabilitation...

  13. Impact of previous virological treatment failures and adherence on the outcome of antiretroviral therapy in 2007.

    Directory of Open Access Journals (Sweden)

    Marie Ballif

    Full Text Available BACKGROUND: Combination antiretroviral treatment (cART has been very successful, especially among selected patients in clinical trials. The aim of this study was to describe outcomes of cART on the population level in a large national cohort. METHODS: Characteristics of participants of the Swiss HIV Cohort Study on stable cART at two semiannual visits in 2007 were analyzed with respect to era of treatment initiation, number of previous virologically failed regimens and self reported adherence. Starting ART in the mono/dual era before HIV-1 RNA assays became available was counted as one failed regimen. Logistic regression was used to identify risk factors for virological failure between the two consecutive visits. RESULTS: Of 4541 patients 31.2% and 68.8% had initiated therapy in the mono/dual and cART era, respectively, and been on treatment for a median of 11.7 vs. 5.7 years. At visit 1 in 2007, the mean number of previous failed regimens was 3.2 vs. 0.5 and the viral load was undetectable (4 previous failures compared to 1 were 0.9 (95% CI 0.4-1.7, 0.8 (0.4-1.6, 1.6 (0.8-3.2, 3.3 (1.7-6.6 respectively, and 2.3 (1.1-4.8 for >2 missed cART doses during the last month, compared to perfect adherence. From the cART era, odds ratios with a history of 1, 2 and >2 previous failures compared to none were 1.8 (95% CI 1.3-2.5, 2.8 (1.7-4.5 and 7.8 (4.5-13.5, respectively, and 2.8 (1.6-4.8 for >2 missed cART doses during the last month, compared to perfect adherence. CONCLUSIONS: A higher number of previous virologically failed regimens, and imperfect adherence to therapy were independent predictors of imminent virological failure.

  14. The future of pharmacogenetics in the treatment of heart failure.

    Science.gov (United States)

    Anwar, Mohamed Subhan; Iskandar, Muhammad Zaid; Parry, Helen M; Doney, Alex S; Palmer, Colin N; Lang, Chim C

    2015-11-01

    Heart failure is a common disease with high levels of morbidity and mortality. Current treatment comprises β-blockers, ACE inhibitors, aldosterone antagonists and diuretics. Variation in clinical response seen in patients begs the question of whether there is a pharmacogenetic component yet to be identified. To date, the genes most studied involve the β-1, β-2, α-2 adrenergic receptors and the renin-angiotensin-aldosterone pathway, mainly focusing on SNPs. However results have been inconsistent. Genome-wide association studies and next-generation sequencing are seen as alternative approaches to discovering genetic variations influencing drug response. Hopefully future research will lay the foundations for genotype-led drug management in these patients with the ultimate aim of improving their clinical outcome.

  15. Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa.

    Directory of Open Access Journals (Sweden)

    Julie H Levison

    Full Text Available We investigated the prevalence of wild-type virus (no major drug resistance and drug resistance mutations at second-line antiretroviral treatment (ART failure in a large HIV treatment program in South Africa.HIV-infected patients ≥ 15 years of age who had failed protease inhibitor (PI-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%. Mean duration on ART (SD prior to initiation of second-line ART was 23 (17 months, and time from second-line ART initiation to failure was 10 (9 months. Plasma samples were obtained 7(9 months from confirmed failure. At second-line failure, 22 patients (67% had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5 months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged.Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.

  16. Enhancing Treatment Outcome of Patients at Risk of Treatment Failure: Meta-Analytic and Mega-Analytic Review of a Psychotherapy Quality Assurance System

    Science.gov (United States)

    Shimokawa, Kenichi; Lambert, Michael J.; Smart, David W.

    2010-01-01

    Objective: Outcome research has documented worsening among a minority of the patient population (5% to 10%). In this study, we conducted a meta-analytic and mega-analytic review of a psychotherapy quality assurance system intended to enhance outcomes in patients at risk of treatment failure. Method: Original data from six major studies conducted…

  17. Dialysis Arteriovenous Fistula Failure and Angioplasty: Intimal Hyperplasia and Other Causes of Access Failure

    Science.gov (United States)

    Duque, Juan C.; Tabbara, Marwan; Martinez, Laisel; Cardona, Jose; Vazquez-Padron, Roberto I; Salman, Loay H

    2016-01-01

    Arteriovenous fistula (AVF) is the preferred hemodialysis access type because it has better patency rates and fewer complications than other access types. However, primary failure remains a common problem impeding AVF maturation and adding to patients’ morbidity and mortality. Juxta-anastomotic (or inflow) stenosis is the most common reason leading to primary failure, and percutaneous transluminal angioplasty (PTA) continues to be the gold standard treatment with excellent success rates. Intimal hyperplasia (IH) has been traditionally blamed as the main pathophysiologic culprit, but new evidence raises doubts regarding the contribution of IH alone to primary failure. We report a 64-year-old man with a two-stage brachio-basilic AVF that was complicated by failure four months after creation. Angiogram showed multiple juxta-anastomotic and mid-fistula stenotic lesions. PTA was successful in assisting maturation and subsequently cannulating AVF for hemodialysis treatment. We failed to identify the underlying cause of stenosis as biopsy specimens from fistula tissue obtained at the time of transposition revealed no occlusive IH. This case emphasizes the need for additional research on factors contributing to AVF failure besides IH, and highlights the need for more therapeutic options to reduce AVF failure rate. PMID:28084215

  18. Anemia in chronic heart failure : etiology and treatment options

    NARCIS (Netherlands)

    Westenbrink, B. Daan; de Boer, Rudolf A.; Voors, Adriaan A.; van Gilst, Wiek H.; van Veldhuisen, Dirk J.

    Purpose of review Anemia is common in patients with chronic heart failure, and is related to increased morbidity and mortality. The etiology of anemia in heart failure is complex and still not fully resolved. The review will describe current advances in the understanding of the pathophysiology of

  19. Adaptive servo ventilation for central sleep apnoea in heart failure: SERVE-HF on-treatment analysis.

    Science.gov (United States)

    Woehrle, Holger; Cowie, Martin R; Eulenburg, Christine; Suling, Anna; Angermann, Christiane; d'Ortho, Marie-Pia; Erdmann, Erland; Levy, Patrick; Simonds, Anita K; Somers, Virend K; Zannad, Faiez; Teschler, Helmut; Wegscheider, Karl

    2017-08-01

    This on-treatment analysis was conducted to facilitate understanding of mechanisms underlying the increased risk of all-cause and cardiovascular mortality in heart failure patients with reduced ejection fraction and predominant central sleep apnoea randomised to adaptive servo ventilation versus the control group in the SERVE-HF trial.Time-dependent on-treatment analyses were conducted (unadjusted and adjusted for predictive covariates). A comprehensive, time-dependent model was developed to correct for asymmetric selection effects (to minimise bias).The comprehensive model showed increased cardiovascular death hazard ratios during adaptive servo ventilation usage periods, slightly lower than those in the SERVE-HF intention-to-treat analysis. Self-selection bias was evident. Patients randomised to adaptive servo ventilation who crossed over to the control group were at higher risk of cardiovascular death than controls, while control patients with crossover to adaptive servo ventilation showed a trend towards lower risk of cardiovascular death than patients randomised to adaptive servo ventilation. Cardiovascular risk did not increase as nightly adaptive servo ventilation usage increased.On-treatment analysis showed similar results to the SERVE-HF intention-to-treat analysis, with an increased risk of cardiovascular death in heart failure with reduced ejection fraction patients with predominant central sleep apnoea treated with adaptive servo ventilation. Bias is inevitable and needs to be taken into account in any kind of on-treatment analysis in positive airway pressure studies. Copyright ©ERS 2017.

  20. Leishmania Antigenuria to Predict Initial Treatment Failure and Relapse in Visceral Leishmaniasis/HIV Coinfected Patients: An Exploratory Study Nested Within a Clinical Trial in Ethiopia.

    Science.gov (United States)

    van Griensven, Johan; Mengesha, Bewketu; Mekonnen, Tigist; Fikre, Helina; Takele, Yegnasew; Adem, Emebet; Mohammed, Rezika; Ritmeijer, Koert; Vogt, Florian; Adriaensen, Wim; Diro, Ermias

    2018-01-01

    Background: Biomarkers predicting the risk of VL treatment failure and relapse in VL/HIV coinfected patients are needed. Nested within a two-site clinical trial in Ethiopia (2011-2015), we conducted an exploratory study to assess whether (1) levels of Leishmania antigenuria measured at VL diagnosis were associated with initial treatment failure and (2) levels of Leishmania antigenuria at the end of treatment (parasitologically-confirmed cure) were associated with subsequent relapse. Methods: Leishmania antigenuria at VL diagnosis and cure was determined using KAtex urine antigen test and graded as negative (0), weak/moderate (grade 1+/2+) or strongly-positive (3+). Logistic regression and Kaplan-Meier methods were used to assess the association between antigenuria and (1) initial treatment failure, and (2) relapse over the 12 months after cure, respectively. Results: The analysis to predict initial treatment failure included sixty-three coinfected adults [median age: 30 years interquartile range (IQR) 27-35], median CD4 count: 56 cells/μL (IQR 38-113). KAtex results at VL diagnosis were negative in 11 (17%), weak/moderate in 17 (27%) and strongly-positive in 35 (36%). Twenty (32%) patients had parasitologically-confirmed treatment failure, with a risk of failure of 9% (1/11) with KAtex-negative results, 0% (0/17) for KAtex 1+/2+ and 54% (19/35) for KAtex 3+ results. Compared to KAtex-negative patients, KAtex 3+ patients were at increased risk of treatment failure [odds ratio 11.9 (95% CI 1.4-103.0); P : 0.025]. Forty-four patients were included in the analysis to predict relapse [median age: 31 years (IQR 28-35), median CD4 count: 116 cells/μL (IQR 95-181)]. When achieving VL cure, KAtex results were negative in 19 (43%), weak/moderate (1+/2+) in 10 (23%), and strongly positive (3+) in 15 patients (34%). Over the subsequent 12 months, eight out of 44 patients (18%) relapsed. The predicted 1-year relapse risk was 6% for KAtex-negative results, 14% for KAtex 1

  1. [Sacubitril/valsartan, a new and effective treatment for heart failure with reduced ejection fraction].

    Science.gov (United States)

    Senni, Michele; Trimarco, Bruno; Emdin, Michele; De Biase, Luciano

    2017-01-01

    Despite significant therapeutic advances, patients with chronic heart failure and reduced ejection fraction (HFrEF) remain at high risk for heart failure progression and death. The PARADIGM-HF study, the largest outcome trial in HFrEF, has shown improved cardiovascular outcomes with sacubitril/valsartan (Entresto®, Novartis), previously known as LCZ696, compared with angiotensin-converting enzyme (ACE) inhibitor therapy, possibly leading us to a new era for heart failure treatment. Sacubitril/valsartan represents a first-in-class drug acting through inhibition of angiotensin receptor and neprilysin, thus modulating the renin-angiotensin-aldosterone system and vasoactive substances such as natriuretic peptides. This approach can be considered a "paradigm shift" from neurohumoral inhibition to neurohumoral modulation. Based on the PARADIGM-HF results, the European Society of Cardiology and the American Heart Association/American College of Cardiology guidelines proposed a substitution of ACE-inhibitor/angiotensin receptor blocker therapy rather than an "add-on" strategy in HFrEF. Sacubitril/valsartan can be considered a milestone in cardiovascular therapy, like aspirin, statins, beta-blockers. Of course there are many questions that arise spontaneously from this trial, three recognized experts can help us to answer them.

  2. Heart Failure in Women

    Science.gov (United States)

    Bozkurt, Biykem; Khalaf, Shaden

    2017-01-01

    Heart failure is an important cause of morbidity and mortality in women, and they tend to develop it at an older age compared to men. Heart failure with preserved ejection fraction is more common in women than in men and accounts for at least half the cases of heart failure in women. When comparing men and women who have heart failure and a low left ventricular ejection fraction, the women are more symptomatic and have a similarly poor outcome. Overall recommendations for guideline-directed medical therapies show no differences in treatment approaches between men and women. Overall, women are generally underrepresented in clinical trials for heart failure. Further studies are needed to shed light into different mechanisms, causes, and targeted therapies of heart failure in women. PMID:29744014

  3. Nkx2.5 enhances the efficacy of mesenchymal stem cells transplantation in treatment heart failure in rats.

    Science.gov (United States)

    Deng, Bo; Wang, Jin Xin; Hu, Xing Xing; Duan, Peng; Wang, Lin; Li, Yang; Zhu, Qing Lei

    2017-08-01

    The aim of this study is to determine whether Nkx2.5 transfection of transplanted bone marrow mesenchymal stem cells (MSCs) improves the efficacy of treatment of adriamycin-induced heart failure in a rat model. Nkx2.5 was transfected in MSCs by lentiviral vector transduction. The expressions of Nkx2.5 and cardiac specific genes in MSCs and Nkx2.5 transfected mesenchymal stem cells (MSCs-Nkx2.5) were analyzed with quantitative real-time PCR and Western blot in vitro. Heart failure models of rats were induced by adriamycin and were then randomly divided into 3 groups: injected saline, MSCs or MSCs-Nkx2.5 via the femoral vein respectively. Four weeks after injection, the cardiac function, expressions of cardiac specific gene, fibrosis formation and collagen volume fraction in the myocardium as well as the expressions of GATA4 and MEF2 in rats were analyzed with echocardiography, immunohistochemistry, Masson staining, quantitative real-time PCR and Western blot, respectively. Nkx2.5 enhanced cardiac specific gene expressions including α-MHC, TNI, CKMB, connexin-43 in MSCs-Nkx2.5 in vitro. Both MSCs and MSCs-Nkx2.5 improved cardiac function, promoted the differentiation of transplanted MSCs into cardiomyocyte-like cells, decreased fibrosis formation and collagen volume fraction in the myocardium, as well as increased the expressions of GATA4 and MEF2 in adriamycin-induced rat heart failure models. Moreover, the effect was much more remarkable in MSCs-Nkx2.5 than in MSCs group. This study has found that Nkx2.5 enhances the efficacy of MSCs transplantation in treatment adriamycin-induced heart failure in rats. Nkx2.5 transfected to transplanted MSCs provides a potential effective approach to heart failure. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Varying effects of recommended treatments for heart failure with reduced ejection fraction

    DEFF Research Database (Denmark)

    Thomsen, Marius Mark; Lewinter, Christian; Køber, Lars

    2016-01-01

    The aim of this paper is to evaluate the treatment effects of recommended drugs and devices on key clinical outcomes for patients with heart failure with reduced ejection fraction (HFREF). Randomized controlled trials (RCTs) listed in the 2012 HF guideline from the European Society of Cardiology...... as well as the 2013 HF guideline from the American College of Cardiology Foundation and American Heart Association were evaluated for use in the meta-analysis. RCTs written in English evaluating recommended drugs and devices for the treatment of patients with HFREF were included. Meta-analyses, based...... on the outcomes of all-cause mortality and hospitalization because of HF, were performed with relative risk ratio as the effect size. In the identified 47 RCTs, patients were on average 63 years old and 22% were female. Drugs targeting the renin-angiotensin-aldosterone system, beta-blockers, cardiac...

  5. In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT

    International Nuclear Information System (INIS)

    Kassiou, Michael; Eberl, Stefan; Meikle, Steven R.; Birrell, Alex; Constable, Chris; Fulham, Michael J.; Wong, Dean F.; Musachio, John L.

    2001-01-01

    To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[ 123 I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[ 123 I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V d ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V d was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V d or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment

  6. Modification of in vitro and in vivo BCG cell wall-induced immunosuppression by treatment with chemotherapeutic agents or indomethacin

    International Nuclear Information System (INIS)

    DeSilva, M.A.; Wepsic, H.T.; Mizushima, Y.; Nikcevich, D.A.; Larson, C.H.

    1985-01-01

    The in vitro inhibition of spleen cell blastogenesis response and the in vivo enhancement of tumor growth are phenomena associated with BCG cell wall (BCGcw) immunization. What effect treatment with chemotherapeutic agents and the prostaglandin inhibitor indomethacin would have on the in vitro and in vivo responses to BCGcw immunization was evaluated. In vitro blastogenesis studies showed that chemotherapy pretreatment prior to immunization with BCGcw resulted in a restoration of the spleen cell blastogenesis response. In blastogenesis addback studies, where BCGcw-induced irradiated splenic suppressor cells were admixed with normal cells, less inhibition of blastogenesis occurred when spleen cells were obtained from rats that had received the combined treatment of chemotherapy and BCGcw immunization versus only BCGcw immunization. The cocultivation of spleen cells from BCGcw-immunized rats with indomethacin resulted in a 30-40% restoration of the blastogenesis response. In vivo studies showed that BCGcw-mediated enhancement of intramuscular tumor growth of the 3924a ACI rat tumor could be abrogated by either pretreatment with busulfan or mitomycin or by the feeding of indomethacin

  7. The Use of a Novel Heart Failure Agent in the Treatment of Pregnancy-Associated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Vamsi C. Gaddipati

    2017-01-01

    Full Text Available Peripartum cardiomyopathy is an uncommon, pregnancy-related form of dilated cardiomyopathy that is associated with development of new-onset left ventricular dysfunction. Its etiology is presently unknown, but current standard of care involves the use of typical drug therapy for the treatment of heart failure. Pregnancy-associated cardiomyopathy (PACM is a similar condition that refers to patients who develop such symptoms prior to the last month of pregnancy. We report the case of a nulliparous Caucasian female who develops early, severe PACM during her first pregnancy with postpartum persistence of New York Heart Association class II-III symptoms despite medical therapy. The use of the novel heart failure agent, sacubitril/valsartan (Entresto, is initiated with near-complete resolution of her symptoms.

  8. Prevalence, prognostic significance, and treatment of atrial fibrillation in congestive heart failure with particular reference to the DIAMOND-CHF study

    DEFF Research Database (Denmark)

    Pedersen, Ole Dyg; Brendorp, Bente; Køber, Lars

    2003-01-01

    Atrial fibrillation is a growing health problem and the most common cardiac arrhythmia, affecting 5% of persons above the age of 65 years. The number of hospital discharges for atrial fibrillation has more than doubled in the past decade. It occurs very often in patients with congestive heart...... failure and the prevalence increases with the severity of the disease. These two conditions seem to be linked together, and congestive heart failure may either be the cause or the consequence of atrial fibrillation. The prognosis of atrial fibrillation is controversial, but studies indicate that atrial...... fibrillation is a risk factor in congestive heart failure patients. In the last 10-15 years, significant advances in the treatment of heart failure have improved survival, whereas effective management of atrial fibrillation in heart failure patients still awaits similar progress. Empirically, two strategies...

  9. Failure mode and effect analysis oriented to risk-reduction interventions in intraoperative electron radiation therapy: The specific impact of patient transportation, automation, and treatment planning availability

    International Nuclear Information System (INIS)

    López-Tarjuelo, Juan; Bouché-Babiloni, Ana; Santos-Serra, Agustín; Morillo-Macías, Virginia; Calvo, Felipe A.; Kubyshin, Yuri

    2014-01-01

    Background and purpose: Industrial companies use failure mode and effect analysis (FMEA) to improve quality. Our objective was to describe an FMEA and subsequent interventions for an automated intraoperative electron radiotherapy (IOERT) procedure with computed tomography simulation, pre-planning, and a fixed conventional linear accelerator. Material and methods: A process map, an FMEA, and a fault tree analysis are reported. The equipment considered was the radiance treatment planning system (TPS), the Elekta Precise linac, and TN-502RDM-H metal–oxide-semiconductor-field-effect transistor in vivo dosimeters. Computerized order-entry and treatment-automation were also analyzed. Results: Fifty-seven potential modes and effects were identified and classified into ‘treatment cancellation’ and ‘delivering an unintended dose’. They were graded from ‘inconvenience’ or ‘suboptimal treatment’ to ‘total cancellation’ or ‘potentially wrong’ or ‘very wrong administered dose’, although these latter effects were never experienced. Risk priority numbers (RPNs) ranged from 3 to 324 and totaled 4804. After interventions such as double checking, interlocking, automation, and structural changes the final total RPN was reduced to 1320. Conclusions: FMEA is crucial for prioritizing risk-reduction interventions. In a semi-surgical procedure like IOERT double checking has the potential to reduce risk and improve quality. Interlocks and automation should also be implemented to increase the safety of the procedure

  10. Characteristics and intraoperative treatments associated with head and neck free tissue transfer complications and failures.

    Science.gov (United States)

    Hand, William R; McSwain, Julie R; McEvoy, Matthew D; Wolf, Bethany; Algendy, Abdalrahman A; Parks, Matthew D; Murray, John L; Reeves, Scott T

    2015-03-01

    To investigate the association between perioperative patient characteristics and treatment modalities (eg, vasopressor use and volume of fluid administration) with complications and failure rates in patients undergoing head and neck free tissue transfer (FTT). A retrospective review of medical records. Perioperative hospitalization for head and neck FTT at 1 tertiary care medical center between January 1, 2009, and October 31, 2011. Consecutive patients (N=235) who underwent head and neck FTT. Demographic, patient characteristic, and intraoperative data were extracted from medical records. Complication and failure rates within the first 30 days were collected In a multivariate analysis controlling for age, sex, ethnicity, reason for receiving flap, and type and volume of fluid given, perioperative complication was significantly associated with surgical blood loss (P=.019; 95% confidence interval [CI], 1.01-1.16), while the rate of intraoperative fluid administration did not reach statistical significance (P=.06; 95% CI, 0.99-1.28). In a univariate analysis, FTT failure was significantly associated with reason for surgery (odds ratio, 5.40; P=.03; 95% CI, 1.69-17.3) and preoperative diagnosis of coronary artery disease (odds ratio, 3.60; P=.03; 95% CI, 1.16-11.2). Intraoperative vasopressor administration was not associated with either FTT complication or failure rate. FTT complications were associated with surgical blood loss but not the use of vasoactive drugs. For patients undergoing FTT, judicious monitoring of blood loss may help stratify the risk of complication and failure. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  11. Tumor-derived exosomes in cancer progression and treatment failure

    Science.gov (United States)

    Shen, Bo; Feng, Jifeng

    2015-01-01

    Exosomes have diameter within the range of 30-100nm and spherical to cup-shaped nanoparticles with specific surface molecular characteristics, such as CD9 and CD63. These vesicles are present in nearly all human body fluids, including blood plasma/serum, saliva, breast milk, cerebrospinal fluid, urine, semen, and particularly enriched in tumor microenvironment. Exosomes contain multiple proteins, DNA, mRNA, miRNA, long non-coding RNA, and even genetic materials of viruses/prions. These materials are biochemically and functionally distinct and can be transferred to a recipient cell where they regulate protein expression and signaling pathways. Recently, exosomes are demonstrated to have a close relationship with tumor development and metastasis. Exosomes influence therapeutic effect in cancer patients. In this review, we describe the biogenesis, composition, and function of exosomes. The mechanism on how tumor-derived exosomes contribute to cancer progression and clinical treatment failure is also described, with special focus on their potential applications in cancer therapy. PMID:26452221

  12. Tumor-derived exosomes in cancer progression and treatment failure.

    Science.gov (United States)

    Yu, Shaorong; Cao, Haixia; Shen, Bo; Feng, Jifeng

    2015-11-10

    Exosomes have diameter within the range of 30-100 nm and spherical to cup-shaped nanoparticles with specific surface molecular characteristics, such as CD9 and CD63. These vesicles are present in nearly all human body fluids, including blood plasma/serum, saliva, breast milk, cerebrospinal fluid, urine, semen, and particularly enriched in tumor microenvironment. Exosomes contain multiple proteins, DNA, mRNA, miRNA, long non-coding RNA, and even genetic materials of viruses/prions. These materials are biochemically and functionally distinct and can be transferred to a recipient cell where they regulate protein expression and signaling pathways. Recently, exosomes are demonstrated to have a close relationship with tumor development and metastasis. Exosomes influence therapeutic effect in cancer patients. In this review, we describe the biogenesis, composition, and function of exosomes. The mechanism on how tumor-derived exosomes contribute to cancer progression and clinical treatment failure is also described, with special focus on their potential applications in cancer therapy.

  13. Advancement Flap for Treatment of Complex Cryptoglandular Anal Fistula: Prediction of Therapy Success or Failure Using Anamnestic and Clinical Parameters.

    Science.gov (United States)

    Boenicke, Lars; Karsten, Eduard; Zirngibl, Hubert; Ambe, Peter

    2017-09-01

    Multiple new procedures for treatment of complex anal fistula have been described in the past decades, but an ideal single technique has yet not been identified. Factors that predict the outcome are required to identify the best procedure for each individual patient. The aim of this study was to find those predictors for advancement flap at midterm follow-up. From 2012 to 2015 in a tertiary university clinic, all patients who underwent advancement flap for treatment of complex cryptoglandular fistula were prospectively enrolled. Pre- and postoperatively standardized anamnestic and clinical examinations were performed. Predictive factors for therapy failure were identified using univariate and multivariate analysis. Out of 65 patients, 61 (93%) completed all examinations and were included in the study. Therapy failure after a mean follow-up period of 25 months occurred in total n = 11 patients (18%). There was no significant disturbance of continence among the entire study cohort as shown by the incontinence score (preop 0.34 ± 0.91 pts., postop 0.37 ± 0.97 pts.; p = 0.59). Univariate analysis for risk factors for therapy failure revealed age (p = 0.004), history of surgical abscess drainage (p = 0.04), BMI (p = 0.002), suprasphincteric fistula (p = 0.019) and horseshoe abscess (p = 0.036) as independent parameters for therapy failure. During multivariate analysis, only history of surgical abscess drainage (OR = 8.09, p = 0.048, 95% CI 0.98-64.96), suprasphincteric fistula (OR = 6.83, p = 0.032, 95% CI 1.17-6.83) and BMI (OR = 1.23, p = 0.017, 95% CI 1.03-1.46) were independent parameters for therapy failure. Advancement flap for treatment of complex fistula is effective and has low risk of disturbed continence. BMI, suprasphincteric fistula and history of surgical abscess drainage are predictors for therapy failure.

  14. Predominant Api m 10 sensitization as risk factor for treatment failure in honey bee venom immunotherapy.

    Science.gov (United States)

    Frick, Marcel; Fischer, Jörg; Helbling, Arthur; Ruëff, Franziska; Wieczorek, Dorothea; Ollert, Markus; Pfützner, Wolfgang; Müller, Sabine; Huss-Marp, Johannes; Dorn, Britta; Biedermann, Tilo; Lidholm, Jonas; Ruecker, Gerta; Bantleon, Frank; Miehe, Michaela; Spillner, Edzard; Jakob, Thilo

    2016-12-01

    Component resolution recently identified distinct sensitization profiles in honey bee venom (HBV) allergy, some of which were dominated by specific IgE to Api m 3 and/or Api m 10, which have been reported to be underrepresented in therapeutic HBV preparations. We performed a retrospective analysis of component-resolved sensitization profiles in HBV-allergic patients and association with treatment outcome. HBV-allergic patients who had undergone controlled honey bee sting challenge after at least 6 months of HBV immunotherapy (n = 115) were included and classified as responder (n = 79) or treatment failure (n = 36) on the basis of absence or presence of systemic allergic reactions upon sting challenge. IgE reactivity to a panel of HBV allergens was analyzed in sera obtained before immunotherapy and before sting challenge. No differences were observed between responders and nonresponders regarding levels of IgE sensitization to Api m 1, Api m 2, Api m 3, and Api m 5. In contrast, Api m 10 specific IgE was moderately but significantly increased in nonresponders. Predominant Api m 10 sensitization (>50% of specific IgE to HBV) was the best discriminator (specificity, 95%; sensitivity, 25%) with an odds ratio of 8.444 (2.127-33.53; P = .0013) for treatment failure. Some but not all therapeutic HBV preparations displayed a lack of Api m 10, whereas Api m 1 and Api m 3 immunoreactivity was comparable to that of crude HBV. In line with this, significant Api m 10 sIgG 4 induction was observed only in those patients who were treated with HBV in which Api m 10 was detectable. Component-resolved sensitization profiles in HBV allergy suggest predominant IgE sensitization to Api m 10 as a risk factor for treatment failure in HBV immunotherapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Retrospective Analysis on the Efficacy, Safety and Treatment Failure Group of Sitagliptin for Mean 10-Month Duration

    Directory of Open Access Journals (Sweden)

    Won Jun Kim

    2011-06-01

    Full Text Available BackgroundTo investigate the clinical results of sitagliptin (SITA and the characteristics of the treatment failure group or of low responders to SITA.MethodsA retrospective study of type 2 diabetic patients reviewed 99 cases, including 12 treatment failure cases, who stopped SITA because of worsening patients' condition, and 87 cases, who continued treatment over five visits (total 9.9±10.1 months after receiving the prescription of SITA from December 2008 to June 2009. Subjects were classified as five groups administered SITA as an initial combination with metformin (MET, add-on to metformin or sulfonylurea, and switching from sulfonylurea or thiazolidinedione. The changes in HbA1c level from the first to last visit (ΔHbA1c in treatment maintenance group were subanalyzed.ResultsThe HbA1c level was significantly reduced in four groups, including initial coadministration of SITA with metformin (ΔHbA1c=-1.1%, P<0.001, add-on to MET (ΔHbA1c=-0.6%, P=0.017, add-on to sulfonylurea (ΔHbA1c=-0.5%, P<0.001, and switching from thiazolidinedione (ΔHbA1c=-0.3%, P=0.013. SITA was noninferior to sulfonlyurea (ΔHbA1c=-0.2%, P=0.63. There was no significant adverse effect. The treatment failure group had a longer diabeties duration (P=0.008, higher HbA1c (P=0.001 and fasting plasma glucose (P=0.003 compared to the maintenance group. Subanalysis on the tertiles of ΔHbA1c showed that low-response to SITA (tertile 1 was associated with a longer diabetes duration (P=0.009 and lower HbA1c (P<0.001.ConclusionSITA was effective and safe for use in Korean type 2 diabetic patients. However, its clinical responses and long-term benefit-harm profile is yet to be established.

  16. Respiratory failure following anti-lung serum: study on mechanisms associated with surfactant system damage

    International Nuclear Information System (INIS)

    Lachmann, B.; Hallman, M.; Bergmann, K.C.

    1987-01-01

    Within 2 minutes intravenous anti-lung serum (ALS) into guinea pig induces a respiratory failure that is fatal within 30 min. The relationship between surfactant, alveolar-capillary permeability and respiratory failure was studied. Within two minutes ALS induced a leak in the alveolar-capillary barrier. Within 30 minutes 28.3% (controls, given normal rabbit serum: 0.7%) of iv 131 I-albumin, and 0.5% (controls 0.02%) of iv surfactant phospholipid tracer were recovered in bronchoalveolar lavage. Furthermore, 57% (controls 32%) of the endotracheally administered surfactant phospholipid became associated with lung tissue and only less than 0.5% left the lung. The distribution of proteins and phospholipids between the in vivo small volume bronchoalveolar lavages and the ex vivo bronchoalveolar lavages were dissimilar: 84% (controls 20%) of intravenously injected, lavageable 131 I-albumin and 23% (controls 18%) of total lavageable phospholipid were recovered in the in vivo small volume bronchoalveolar lavages. ALS also decreased lavageable surfactant phospholipid by 41%. After ALS the minimum surface tension increased. The supernatant of the lavage increased the minimum surface tension of normal surfactant. In addition, the sediment fraction of the lavage had slow surface adsorption, and a marked reduction in 35,000 and 10,000 MW peptides. Exogenous surfactant ameliorated the ALS-induced respiratory failure. We propose that inhibition, altered intrapulmonary distribution, and dissociation of protein and phospholipid components of surfactant are important in early pathogenesis of acute respiratory failure

  17. Quality aspects of ex vivo root canal treatments done by undergraduate dental students using four different endodontic treatment systems.

    Science.gov (United States)

    Jungnickel, Luise; Kruse, Casper; Vaeth, Michael; Kirkevang, Lise-Lotte

    2018-04-01

    To evaluate factors associated with treatment quality of ex vivo root canal treatments performed by undergraduate dental students using different endodontic treatment systems. Four students performed root canal treatment on 80 extracted human teeth using four endodontic treatment systems in designated treatment order following a Latin square design. Lateral seal and length of root canal fillings was radiographically assessed; for lateral seal, a graded visual scale was used. Treatment time was measured separately for access preparation, biomechanical root canal preparation, obturation and for the total procedure. Mishaps were registered. An ANOVA mirroring the Latin square design was performed. Use of machine-driven nickel-titanium systems resulted in overall better quality scores for lateral seal than use of the manual stainless-steel system. Among systems with machine-driven files, scores did not significantly differ. Use of machine-driven instruments resulted in shorter treatment time than manual instrumentation. Machine-driven systems with few files achieved shorter treatment times. With increasing number of treatments, root canal-filling quality increased, treatment time decreased; a learning curve was plotted. No root canal shaping file separated. The use of endodontic treatment systems with machine-driven files led to higher quality lateral seal compared to the manual system. The three contemporary machine-driven systems delivered comparable results regarding quality of root canal fillings; they were safe to use and provided a more efficient workflow than the manual technique. Increasing experience had a positive impact on the quality of root canal fillings while treatment time decreased.

  18. In vivo and ex vivo characterization of a novel Er fiber laser system for fractional treatment of soft oral tissues

    Science.gov (United States)

    Shatilova, Ksenia; Aloian, Georgii; Karabut, Maria; Ryabova, Valentina; Yaroslavsky, Ilya V.; Altshuler, Gregory

    2018-02-01

    In this work, we present the first histological in vivo and ex vivo study of effects of fractional Er fiber laser (wavelength 1550 nm, peak power 25 W) on keratinized gum and alveolar mucosa for gum regeneration. Biopsy with subsequent NBTC staining was used as primary evaluation technique. Ex vivo, porcine tissue model was used. Effects of pulse energy, beam diameter, and beam divergence were investigated in detail. It has been demonstrated that under optimal conditions columns up to 800 μm in depth could be reliably produced with 130 mJ pulses. Clinically, 2 subjects were treated and 4 punch biopsies were collected. The results were compared with ex vivo data. Both ex vivo and in vivo datasets suggest feasibility of a dental fractional system intended for gum regeneration.

  19. Characteristics of failure to thrive in a referral population: implications for treatment.

    Science.gov (United States)

    Atalay, Alev; McCord, Mary

    2012-03-01

    Failure to thrive (FTT) in children is an important pediatric problem. Environmental and behavioral causes predominate, and detrimental effects on neurocognitive development are well documented. Multidisciplinary clinics designed to identify and treat FTT are effective but have not been widely adopted. A retrospective chart review was conducted of all patients with FTT seen at the authors' large inner-city children's hospital over a 40-month period, including those referred to a new multidisciplinary clinic. Over 40 months, only 75 children were referred and only 20 had moderate or severe FTT (z-score <-2.0). Nutritional status improved with treatment, but the small number of referrals who were severely affected led to the closing of the clinic. Recommendations for evaluating and treating children with mild FTT in primary care settings and a standardized definition of FTT that warrants more intensive treatment would help ensure that children were referred and treated appropriately.

  20. Beneficial Effect of Paljeong-san Pharmacopuncture Treatment Combined with Peritoneal Injection on Glycerol-Induced Acute Renal Failure in Rabbits

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    Chi-Yeon Lim

    2010-09-01

    Full Text Available Purpose: The present study was carried out to determine if Paljeong-san extract (PJS treatment exerts beneficial effect against the glycerol-induced acute renal failure in rabbits. Material and Method: PJS was selected in the basis of invigorating kidney which can eliminate pathogens. Rabbits were treated with PJS pharmacopuncture on Shin-shu (BL23 point for 5 days right after the injection of 50% concentration of glycerol (5㎖/㎏ body weight. Results and Conclusions: Glycerol injection caused an increase in serum creatinine and BUN level and urine glucose secretion, which were accompanied by a reduction in GFR. PJS Pharmacopuncture treatment combined with peritoneal injection showed beneficial effect on glycerol-induced acute renal failure by inhibition of serum creatinine increase and GFR decrease.

  1. Study of in vitro toxicity and ex vivo and in vivo efficiency of calixarene galenic forms developed for the treatment of cutaneous contamination due to uranium compounds

    International Nuclear Information System (INIS)

    Grives, Sophie

    2015-01-01

    In case of radiological skin contamination by uranium compounds, the only treatments currently available consist in rinsing the contaminated skin area with water and detergent, or with a calcium salt of diethylene triamine pentaacetic acid (Ca-DTPA) solution. However, these procedures are not specific and no efficient treatment for cutaneous contamination due to uranium exists. In the absence of such treatments, uranium diffusion through the skin is fast, inducing an internal exposure after its distribution inside the body through the bloodstream. One part of the bioavailable uranium is up-taken in target organs which are the kidneys and the skeleton, where its toxic effects occur. Therefore a topical formulation consisting of an oil-in-water nano-emulsion incorporating a tricarboxylic calixarene molecule, as a specific chelating agent for uranium, was previously developed. The work achieved in this thesis aimed at evaluating the ex vivo and in vivo decontamination efficiency of this new emergency treatment on intact and superficially wounded skin. For this purpose, skin excoriation model was used. Reproducible models of superficial wounds consisting of micro-cuts and micro-punctures were also developed in order to evaluate the efficiency of the nano-emulsion on physical wounds such as incisions. These studies showed that the calixarene nano-emulsion could be an efficient decontaminating treatment, less aggressive than using the current treatment: soaped water. Its potential cutaneous toxicity was evaluated on in vitro reconstructed human epidermis using three different toxicity tests (MTT, LDH and IL-1-α). These studies demonstrated that the calixarene nano-emulsion did not induce skin toxicity even after 24 h of exposure time. (author)

  2. Effect of Shenkang injection combined with hemodialysis treatment on renal function, renal anemia and cytokine levels in patients with chronic renal failure

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    Rui Liu

    2016-10-01

    Full Text Available Objective: To study the effect of Shenkang injection combined with hemodialysis treatment on renal function, renal anemia and cytokine levels in patients with chronic renal failure. Methods: A total of 68 patients with chronic renal failure who received hemodialysis treatment in our hospital during between October 2013 and February 2016 were selected and randomly divided into two groups, the observation group received Shenkang injection treatment in the process of dialysis, and the control group only received conventional symptomatic and supportive treatment. 8 weeks after treatment, serum was collected to determine the levels of renal function indexes, nutritional status indexes, anemia indexes and cytokines, and urine was collected to determine renal function indexes. Results: β2-MG, UA, Cr, phosphorus, IL-17, IL-23, CTGF, TGF-β1, FGF-2 and FGF-23 levels in serum as well as NGAL, KIM-1 and RBP levels in urine of observation group were significantly lower than those of control group, and TP, Alb, PA, calcium, Hb, EPO, Fe, TRF and FER levels in serum were significantly higher than those of control group. Conclusion: Shenkang injection combined with hemodialysis treatment helps to improve renal function, nutritional status and renal anemia, and reduce the synthesis of inflammation and renal interstitial fibrosis-related cytokines in patients with chronic renal failure.

  3. Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology.

    Science.gov (United States)

    Gorter, Thomas M; van Veldhuisen, Dirk J; Bauersachs, Johann; Borlaug, Barry A; Celutkiene, Jelena; Coats, Andrew J S; Crespo-Leiro, Marisa G; Guazzi, Marco; Harjola, Veli-Pekka; Heymans, Stephane; Hill, Loreena; Lainscak, Mitja; Lam, Carolyn S P; Lund, Lars H; Lyon, Alexander R; Mebazaa, Alexandre; Mueller, Christian; Paulus, Walter J; Pieske, Burkert; Piepoli, Massimo F; Ruschitzka, Frank; Rutten, Frans H; Seferovic, Petar M; Solomon, Scott D; Shah, Sanjiv J; Triposkiadis, Filippos; Wachter, Rolf; Tschöpe, Carsten; de Boer, Rudolf A

    2018-01-01

    There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

  4. Focus on renal congestion in heart failure.

    Science.gov (United States)

    Afsar, Baris; Ortiz, Alberto; Covic, Adrian; Solak, Yalcin; Goldsmith, David; Kanbay, Mehmet

    2016-02-01

    Hospitalizations due to heart failure are increasing steadily despite advances in medicine. Patients hospitalized for worsening heart failure have high mortality in hospital and within the months following discharge. Kidney dysfunction is associated with adverse outcomes in heart failure patients. Recent evidence suggests that both deterioration in kidney function and renal congestion are important prognostic factors in heart failure. Kidney congestion in heart failure results from low cardiac output (forward failure), tubuloglomerular feedback, increased intra-abdominal pressure or increased venous pressure. Regardless of the cause, renal congestion is associated with increased morbidity and mortality in heart failure. The impact on outcomes of renal decongestion strategies that do not compromise renal function should be explored in heart failure. These studies require novel diagnostic markers that identify early renal damage and renal congestion and allow monitoring of treatment responses in order to avoid severe worsening of renal function. In addition, there is an unmet need regarding evidence-based therapeutic management of renal congestion and worsening renal function. In the present review, we summarize the mechanisms, diagnosis, outcomes, prognostic markers and treatment options of renal congestion in heart failure.

  5. Can growth hormone treatment improve growth in children with severe growth failure due to anorexia nervosa? A preliminary pilot study

    Directory of Open Access Journals (Sweden)

    Juliane Léger

    2017-11-01

    Full Text Available Background/Aims: Growth failure is a difficult but key aspect of care in children with anorexia nervosa (AN. The effects of hGH therapy have not been studied. The aim was to investigate the effect of hGH treatment on height velocity (HV in children with AN. Methods: We carried out a retrospective observational study. Ten girls diagnosed with AN at 10.0 ± 1.9 years, with prolonged severe growth failure (HV < 2.5 cm/year for at least 18 months at the age of 13.3 ± 1.1 years and delayed puberty after nutritional rehabilitation, were treated with hGH (0.040 mg/kg/day from a bone age of 10.9 ± 1.7 years until they reached adult height. Height and HV were measured before treatment and at 12-month intervals during treatment. Results: Mean body mass index SDS remained unchanged, but HV increased significantly, from a median of 1.0 (0.7–2.1 to 7.1 (6.0–9.5 cm/year after one year (P < 0.002 and 5.6 (4.8–6.2 cm/year after two years of treatment. Height SDS increased from −2.2 ± 1.3 to −1.6 ± 1.3 after one year (P < 0.002 and −1.1 ± 1.5 after two years of GH treatment. Adult height (−0.1 ± 1.0 SDS was close to target height after 3.6 ± 1.4 years of GH treatment. Serum IGF-I levels increased significantly during treatment (P < 0.01. The treatment was well tolerated. Conclusions: This proof-of-concept study shows that hGH treatment is associated with significant improvements in linear growth in adolescents with AN and severe growth failure. A randomized placebo-controlled trial is required to determine the ultimate impact of GH treatment in patients with this severe, rare condition.

  6. Can We Predict Oral Antibiotic Treatment Failure in Children with Fast-Breathing Pneumonia Managed at the Community Level? A Prospective Cohort Study in Malawi.

    Directory of Open Access Journals (Sweden)

    Carina King

    Full Text Available Pneumonia is the leading cause of infectious death amongst children globally, with the highest burden in Africa. Early identification of children at risk of treatment failure in the community and prompt referral could lower mortality. A number of clinical markers have been independently associated with oral antibiotic failure in childhood pneumonia. This study aimed to develop a prognostic model for fast-breathing pneumonia treatment failure in sub-Saharan Africa.We prospectively followed a cohort of children (2-59 months, diagnosed by community health workers with fast-breathing pneumonia using World Health Organisation (WHO integrated community case management guidelines. Cases were followed at days 5 and 14 by study data collectors, who assessed a range of pre-determined clinical features for treatment outcome. We built the prognostic model using eight pre-defined parameters, using multivariable logistic regression, validated through bootstrapping.We assessed 1,542 cases of which 769 were included (32% ineligible; 19% defaulted. The treatment failure rate was 15% at day 5 and relapse was 4% at day 14. Concurrent malaria diagnosis (OR: 1.62; 95% CI: 1.06, 2.47 and moderate malnutrition (OR: 1.88; 95% CI: 1.09, 3.26 were associated with treatment failure. The model demonstrated poor calibration and discrimination (c-statistic: 0.56.This study suggests that it may be difficult to create a pragmatic community-level prognostic child pneumonia tool based solely on clinical markers and pulse oximetry in an HIV and malaria endemic setting. Further work is needed to identify more accurate and reliable referral algorithms that remain feasible for use by community health workers.

  7. Development of transmission dose estimation algorithm for in vivo dosimetry in high energy radiation treatment

    International Nuclear Information System (INIS)

    Yun, Hyong Geun; Shin, Kyo Chul; Hun, Soon Nyung; Woo, Hong Gyun; Ha, Sung Whan; Lee, Hyoung Koo

    2004-01-01

    In vivo dosimetry is very important for quality assurance purpose in high energy radiation treatment. Measurement of transmission dose is a new method of in vivo dosimetry which is noninvasive and easy for daily performance. This study is to develop a tumor dose estimation algorithm using measured transmission dose for open radiation field. For basic beam data, transmission dose was measured with various field size (FS) of square radiation field, phantom thickness (Tp), and phantom chamber distance (PCD) with a acrylic phantom for 6 MV and 10 MV X-ray. Source to chamber distance (SCD) was set to 150 cm. Measurement was conducted with a 0.6 cc Farmer type ion chamber. By using regression analysis of measured basic beam data, a transmission dose estimation algorithm was developed. Accuracy of the algorithm was tested with flat solid phantom with various thickness in various settings of rectangular fields and various PCD. In our developed algorithm, transmission dose was equated to quadratic function of log(A/P) (where A/P is area-perimeter ratio) and the coefficients of the quadratic functions were equated to tertiary functions of PCD. Our developed algorithm could estimate the radiation dose with the errors within ±0.5% for open square field, and with the errors within ±1.0% for open elongated radiation field. Developed algorithm could accurately estimate the transmission dose in open radiation fields with various treatment settings of high energy radiation treatment. (author)

  8. Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple "sequential" or "concomitant" treatment to eradicate H. pylori infection.

    Science.gov (United States)

    Gisbert, Javier P; Molina-Infante, Javier; Marin, Alicia C; Vinagre, Gemma; Barrio, Jesus; McNicholl, Adrian Gerald

    2013-06-01

    Non-bismuth quadruple "sequential" and "concomitant" regimens, including a proton pump inhibitor (PPI), amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as first-line treatments for Helicobacter pylori infection. Eradication with rescue regimens may be challenging after failure of key antibiotics such as clarithromycin and nitroimidazoles. To evaluate the efficacy and tolerability of a second-line levofloxacin-containing triple regimen (PPI-amoxicillin-levofloxacin) in the eradication of H. pylori after non-bismuth quadruple-containing treatment failure. prospective multicenter study. in whom a non-bismuth quadruple regimen, administered either sequentially (PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for 5 more days) or concomitantly (PPI + amoxicillin + clarithromycin + metronidazole for 10 days) had previously failed. levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and PPI (standard dose b.i.d.) for 10 days. eradication was confirmed with (13)C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. 100 consecutive patients were included (mean age 50 years, 62% females, 12% peptic ulcer and 88% dyspepsia): 37 after "sequential", and 63 after "concomitant" treatment failure. All patients took all medications correctly. Overall, per-protocol and intention-to-treat H. pylori eradication rates were 75.5% (95% CI 66-85%) and 74% (65-83%). Respective intention-to-treat cure rates for "sequential" and "concomitant" failure regimens were 74.4% and 71.4%, respectively. Adverse effects were reported in six (6%) patients; all of them were mild. Ten-day levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous non-bismuth quadruple "sequential" or "concomitant" treatment failure.

  9. The fascial system and exercise intolerance in patients with chronic heart failure: hypothesis of osteopathic treatment

    Directory of Open Access Journals (Sweden)

    Bordoni B

    2015-10-01

    Full Text Available Bruno Bordoni,1–3 F Marelli2,3 1Don Carlo Gnocchi Foundation, Department of Cardiology, IRCCS Santa Maria Nascente, Milan, Italy; 2School CRESO, Osteopathic Centre for Research and Studies, Falconara Marittima, AN, Italy; 3School CRESO, Osteopathic Centre for Research and Studies, Castellanza, VA, Italy Abstract: Chronic heart failure is a progressive, debilitating disease, resulting in a decline in the quality of life of the patient and incurring very high social economic costs. Chronic heart failure is defined as the inability of the heart to meet the demands of oxygen from the peripheral area. It is a multi-aspect complex disease which impacts negatively on all of the body systems. Presently, there are no texts in the modern literature that associate the symptoms of exercise intolerance of the patient with a dysfunction of the fascial system. In the first part of this article, we will discuss the significance of the disease, its causes, and epidemiology. The second part will explain the pathological adaptations of the myofascial system. The last section will outline a possible osteopathic treatment for patients with heart failure in order to encourage research and improve the general curative approach for the patient. Keywords: manual therapy, fatigue, chronic heart failure, osteopathic

  10. Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure

    Science.gov (United States)

    Finosh, G.T.; Jayabalan, Muthu

    2012-01-01

    Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed. PMID:23507781

  11. Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo.

    Science.gov (United States)

    He, Shengwei; Zhao, Wenzhi; Zhang, Lu; Mi, Lidong; Du, Guangyu; Sun, Chuanxiu; Sun, Xuegang

    2017-01-01

    To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo . Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz) were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligan, and pre-collagen type 1 α were measured. Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligand, and pre-collagen type 1 α were also markedly higher following 25 and 50 Hz treatment. Low frequency (25-50 Hz) vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury.

  12. Clinical evaluation of the failure rates of metallic brackets

    Directory of Open Access Journals (Sweden)

    Fábio Lourenço Romano

    2012-04-01

    Full Text Available OBJECTIVES: The aim of this study was to evaluate in vivo the bonding of metallic orthodontic brackets with different adhesive systems. MATERIAL AND METHODS: Twenty patients (10.5-15.1 years old who had sought corrective orthodontic treatment at a University Orthodontic Clinic were evaluated. Brackets were bonded from the right second premolar to the left second premolar in the upper and lower arches using: Orthodontic Concise, conventional Transbond XT, Transbond XT without primer, and Transbond XT associated with Transbond Plus Self-etching Primer (TPSEP. The 4 adhesive systems were used in all patients using a split-mouth design; each adhesive system was used in one quadrant of each dental arch, so that each group of 5 patients received the same bonding sequence. Initial archwires were inserted 1 week after bracket bonding. The number of bracket failures for each adhesive system was quantified over a 6-month period. RESULTS: The number of debonded brackets was: 8- Orthodontic Concise, 2- conventional Transbond XT, 9- Transbond XT without primer, and 1- Transbond XT + TPSEP. By using the Kaplan-Meier methods, statistically significant differences were found between the materials (p=0.0198, and the Logrank test identified these differences. Conventional Transbond XT and Transbond XT + TPSEP adhesive systems were statistically superior to Orthodontic Concise and Transbond XT without primer (p<0.05. There was no statistically significant difference between the dental arches (upper and lower, between the dental arch sides (right and left, and among the quadrants. CONCLUSIONS: The largest number of bracket failures occurred with Orthodontic Concise and Transbond XT without primer systems and few bracket failures occurred with conventional Transbond XT and Transbond XT+TPSEP. More bracket failures were observed in the posterior region compared with the anterior region.

  13. Carvedilol Compared With Metoprolol Succinate in the Treatment and Prognosis of Patients With Stable Chronic Heart Failure: Carvedilol or Metoprolol Evaluation Study.

    Science.gov (United States)

    Fröhlich, Hanna; Zhao, Jingting; Täger, Tobias; Cebola, Rita; Schellberg, Dieter; Katus, Hugo A; Grundtvig, Morten; Hole, Torstein; Atar, Dan; Agewall, Stefan; Frankenstein, Lutz

    2015-09-01

    β-Blockers exert a prognostic benefit in the treatment of chronic heart failure. Their pharmacological properties vary. The only substantial comparative trial to date-the Carvedilol or Metoprolol European Trial-has compared carvedilol with short-acting metoprolol tartrate at different dose equivalents. We therefore addressed the relative efficacy of equal doses of carvedilol and metoprolol succinate on survival in multicenter hospital outpatients with chronic heart failure. Four thousand sixteen patients with stable systolic chronic heart failure who were using either carvedilol or metoprolol succinate were identified in the Norwegian Heart Failure Registry and The Heart Failure Registry of the University of Heidelberg, Germany. Patients were individually matched on both the dose equivalents and the respective propensity scores for β-blocker treatment. During a follow-up for 17 672 patient-years, it was found that 304 (27.2%) patients died in the carvedilol group and 1066 (36.8%) in the metoprolol group. In a univariable analysis of the general sample, metoprolol therapy was associated with higher mortality compared with carvedilol therapy (hazard ratio, 1.49; 95% confidence interval, 1.31-1.69; P<0.001). This difference was not seen after multivariable adjustment (hazard ratio, 0.93; 95% confidence interval, 0.57-1.50; P=0.75) and adjustment for propensity score and dose equivalents (hazard ratio, 1.06; 95% confidence interval, 0.94-1.20; P=0.36) or in the propensity and dose equivalent-matched sample (hazard ratio, 1.00; 95% confidence interval, 0.82-1.23; P=0.99). These results were essentially unchanged for all prespecified subgroups. In outpatients with chronic heart failure, no conclusive association between all-cause mortality and treatment with carvedilol or metoprolol succinate was observed after either multivariable adjustment or multilevel propensity score matching. © 2015 American Heart Association, Inc.

  14. Ivabradine: Current and Future Treatment of Heart Failure.

    Science.gov (United States)

    Thorup, Lene; Simonsen, Ulf; Grimm, Daniela; Hedegaard, Elise R

    2017-08-01

    In heart failure (HF), the heart cannot pump blood efficiently and is therefore unable to meet the body's demands of oxygen, and/or there is increased end-diastolic pressure. Current treatments for HF with reduced ejection fraction (HFrEF) include angiotensin-converting enzyme (ACE) inhibitors, angiotension receptor type 1 (AT 1 ) antagonists, β-adrenoceptor antagonists, aldosterone receptor antagonists, diuretics, digoxin and a combination drug with AT 1 receptor antagonist and neprilysin inhibitor. In HF, the risk of readmission for hospital and mortality is markedly higher with a heart rate (HR) above 70 bpm. Here, we review the evidence regarding the use of ivabradine for lowering HR in HF. Ivabradine is a blocker of an I funny current (I(f)) channel and causes rate-dependent inhibition of the pacemaker activity in the sinoatrial node. In clinical trials of HFrEF, treatment with ivabradine seems to improve clinical outcome, for example improved ejection fraction (EF) and less readmission for hospital, but the effect appears most pronounced in patients with HRs above 70 bpm, while the effect on cardiovascular death appears less consistent. The adverse effects of ivabradine include bradycardia, atrial fibrillation and visual disturbances, but ivabradine avoids the negative inotrope effects observed with β-adrenoceptor antagonists. In conclusion, in patients with stable HFrEF with EF<35% and HR above 70 bpm, ivabradine improves the outcome and might be a first choice of therapy, if beta-adrenoceptor antagonists are not tolerated. Further studies must show whether that can be extended to HF patients with preserved EF. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  15. Statin Treatment and Clinical Outcomes of Heart Failure Among Africans: An Inverse Probability Treatment Weighted Analysis.

    Science.gov (United States)

    Bonsu, Kwadwo Osei; Owusu, Isaac Kofi; Buabeng, Kwame Ohene; Reidpath, Daniel D; Kadirvelu, Amudha

    2017-04-01

    Randomized control trials of statins have not demonstrated significant benefits in outcomes of heart failure (HF). However, randomized control trials may not always be generalizable. The aim was to determine whether statin and statin type-lipophilic or -hydrophilic improve long-term outcomes in Africans with HF. This was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all-cause, cardiovascular, and HF mortality or end of study. Multivariable time-dependent Cox model and inverse-probability-of-treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person-years of observation. Using the time-dependent Cox model, the 5-year adjusted hazard ratios with 95% CI for statin treatment on all-cause, cardiovascular, and HF mortality were 0.68 (0.55-0.83), 0.67 (0.54-0.82), and 0.63 (0.51-0.79), respectively. Use of inverse-probability-of-treatment weighting resulted in estimates of 0.79 (0.65-0.96), 0.77 (0.63-0.96), and 0.77 (0.61-0.95) for statin treatment on all-cause, cardiovascular, and HF mortality, respectively, compared with no statin use. Among Africans with HF, statin treatment was associated with significant reduction in mortality. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  16. Long term outcome of treatment of end stage renal failure.

    Science.gov (United States)

    Henning, P; Tomlinson, L; Rigden, S P; Haycock, G B; Chantler, C

    1988-01-01

    The most common causes of end stage renal failure in 46 children (mean age 11 years, range 4-14) treated between January 1972 and June 1977 were: reflux nephropathy (n = 12), cystinosis (n = 7), focal and segmental glomerulosclerosis (n = 6), and Schönlein-Henoch disease (n = 5). The quality of life, degree of renal function, and height attainment of the 31 survivors were assessed in June 1985, when their mean age was 22 years (range 14-27), using hospital records and a questionnaire designed to highlight social and psychological problems. Twenty six patients had a functioning transplanted kidney. Average growth during treatment for all survivors was normal, but most were disappointed with their 'final height'. Though five patients had some form of disabling bone disease, all 31 could walk and 27 could run. Sixteen (67%) were in full or part time employment and nine were living independently. A group of 32 patients with juvenile onset diabetes treated at this hospital for at least five years were also asked to complete the questionnaire and of these, 17 responded. On average, their data could usefully be compared with those of cases of end stage renal failure. More of the diabetics had jobs, but most sexually mature patients with renal disease were concerned about their physical appearance and had not achieved any stable long term sexual relationships. We suggest that a poor body image resulting in low self esteem may be responsible for the deficiency and believe that further study in this group is warranted.

  17. An evaluation of culture results during treatment for tuberculosis as surrogate endpoints for treatment failure and relapse.

    Directory of Open Access Journals (Sweden)

    Patrick P J Phillips

    Full Text Available It is widely acknowledged that new regimens are urgently needed for the treatment of tuberculosis. The primary endpoint in the Phase III trials is a composite outcome of failure at the end of treatment or relapse after stopping treatment. Such trials are usually both long and expensive. Valid surrogate endpoints measured during or at the end of treatment could dramatically reduce both the time and cost of assessing the effectiveness of new regimens. The objective of this study was to evaluate sputum culture results on solid media during treatment as surrogate endpoints for poor outcome. Data were obtained from twelve randomised controlled trials conducted by the British Medical Research Council in the 1970s and 80s in East Africa and East Asia, consisting of 6974 participants and 49 different treatment regimens. The month two culture result was shown to be a poor surrogate in East Africa but a good surrogate in Hong Kong. In contrast, the month three culture was a good surrogate in trials conducted in East Africa but not in Hong Kong. As well as differences in location, ethnicity and probable strain of Mycobacteria tuberculosis, Hong Kong trials more often evaluated regimens with rifampicin throughout and intermittent regimens, and patients in East African trials more often presented with extensive cavitation and were slower to convert to culture negative during treatment. An endpoint that is a summary measure of the longitudinal profile of culture results over time or that is able to detect the presence of M. tuberculosis later in treatment is more likely to be a better endpoint for a phase II trial than a culture result at a single time point and may prove to be an acceptable surrogate. More data are needed before any endpoint can be used as a surrogate in a confirmatory phase III trial.

  18. Development of an Electronic Medical Record Based Alert for Risk of HIV Treatment Failure in a Low-Resource Setting

    Science.gov (United States)

    Puttkammer, Nancy; Zeliadt, Steven; Balan, Jean Gabriel; Baseman, Janet; Destiné, Rodney; Domerçant, Jean Wysler; France, Garilus; Hyppolite, Nathaelf; Pelletier, Valérie; Raphael, Nernst Atwood; Sherr, Kenneth; Yuhas, Krista; Barnhart, Scott

    2014-01-01

    Background The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART) and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk. Methods Among adult patients enrolled on ART from 2005–2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6–12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves. Results Among 923 patients with CD4 results available during the period 6–12 months after ART initiation, 196 (21.2%) met ART failure criteria. The pharmacy-based proportion of days covered (PDC) measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (pART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation. Conclusions Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs. PMID:25390044

  19. PASSIVE CAVITATION DETECTION DURING PULSED HIFU EXPOSURES OF EX VIVO TISSUES AND IN VIVO MOUSE PANCREATIC TUMORS

    Science.gov (United States)

    Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

    2014-01-01

    Pulsed high-intensity focused ultrasound (pHIFU) has been demonstrated to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rarefactional focal pressures (1–12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms, pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KPC mice and closely recapitulate human disease in their morphology. The cavitation threshold, defined at 50 % cavitation probability, was found to vary broadly among the investigated tissues (within 2.5–10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but ex vivo it decreased rapidly and stopped over the first few pulses

  20. Passive cavitation detection during pulsed HIFU exposures of ex vivo tissues and in vivo mouse pancreatic tumors.

    Science.gov (United States)

    Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

    2014-07-01

    Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1-12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5-10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped

  1. Immune biomarkers of treatment failure for a patient on a phase I clinical trial of pembrolizumab plus radiotherapy

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    Gregory S. Alexander

    2016-09-01

    Full Text Available Abstract Background Pembrolizumab is a monoclonal antibody that is designed against programmed cell death protein 1 (PD-1. Pembrolizumab and other immunocheckpoint-blocking monoclonal antibodies work by modulating a patient’s own immune system to increase anti-tumor activity. While immunocheckpoint blockade has shown promising results, only 20–40 % of patients experience objective clinical benefit. Differences in individual tumor biology and the presence multiple immune checkpoints present a challenge for treatment. Because radiotherapy has immunomodulatory effects on the tumor microenvironment, it has the potential to synergize with immunotherapy and augment tumor response. NCT02318771 is a phase 1 clinical trial designed to investigate the immunomodulatory effects of radiation therapy in combination with pembrolizumab. Case presentation The patient is a 64-year-old male with metastatic clear cell renal cell carcinoma, Fuhrman grade 4, pathologically staged as T3 N0. Metastatic disease was well controlled for several years with sunitinib. Following disease progression, he was switched to axitinib. When disease progression continued, the patient was enrolled in NCT02318771, a phase 1 clinical trial combining radiotherapy and pembrolizumab. The patient experienced unusually rapid disease progression during treatment, which was confirmed by repeated CT scans to rule out pseudoprogression. Tissue biopsies and peripheral blood draws were obtained before, during, and after treatment. Samples were analyzed to provide plausible rationale for rapid treatment failure. Conclusions Biomarker analysis demonstrated an absence of TILs, which may be a cause of treatment failure as pembrolizumab works through T cell-dependent mechanisms. Furthermore, the presence of other non-redundant immune checkpoints in the periphery and tumor microenvironment presents a treatment challenge. Additionally, the radiation dose and fractionation schedule may have played a

  2. Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b.

    Science.gov (United States)

    Kanda, Tatsuo; Nirei, Kazushige; Matsumoto, Naoki; Higuchi, Teruhisa; Nakamura, Hitomi; Yamagami, Hiroaki; Matsuoka, Shunichi; Moriyama, Mitsuhiko

    2017-12-14

    The recent development of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection could lead to higher sustained virological response (SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions (RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1b (GT1b) is founded in 70% of HCV-infected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1b-infected patients with treatment failure.

  3. [Management of heart failure in cardiology and primary care (MICCAP) program: Improving the management of patients with heart failure].

    Science.gov (United States)

    Barrios, V; Escobar, C; Pallares, V; Egocheaga, M I; Lobos, J M; Bover, R; Gómez Doblas, J J; Cosín, J

    2018-03-26

    Despite current treatments, morbidity and mortality of patients with heart failure remain high. The late diagnosis of heart failure, the insufficient heart failure treatment (i.e. not using the appropriate drugs, prescribing lower doses of drugs than recommended, etc.), and a poor coordination between different health care levels, may explain, at least in part, these figures. The Management of Heart Failure in Cardiology and Primary Care (MICCAP) program has been developed with the aim of optimising the integrated management of patients with heart failure between Primary Care and Cardiology, through the improvement of coordination between both health care levels. This includes continuous medical education to reinforce the diagnostic and therapeutic skills of general practitioners in the field of heart failure. The rationale and objectives of the MICCAP program are summarised in this article. Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  4. The Rapid Emergence of Tigecycline Resistance in blaKPC–2 Harboring Klebsiella pneumoniae, as Mediated in Vivo by Mutation in tetA During Tigecycline Treatment

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    Xiaoxing Du

    2018-04-01

    Full Text Available Tigecycline is one of the last resort treatments for carbapenem-resistant Klebsiella pneumoniae (CRKP infections. Tigecycline resistance often occurs during the clinical treatment of CRKP, yet its mechanism has still not been clearly elucidated. This study presents an analysis of a tigecycline resistance mechanism that developed in clinical isolates from a 56-year-old female patient infected with CRKP during tigecycline treatment. Consecutive clonal consistent K. pneumoniae isolates were obtained during tigecycline treatment. Whole genome sequencing of the isolates was performed, and putative single nucleotide polymorphisms and insertion and deletion mutations were analyzed in susceptible and resistant isolates. The identified gene of interest was examined through experiments involving transformations and conjugations. Four isolates, two of which were susceptible and two resistant, were collected from the patient. All of the isolates belonged to Sequence Type 11 (ST11 and were classified as extensively drug resistant (XDR. One amino acid substitution S251A in TetA was identified in the tigecycline-resistant isolates. Subsequent transformation experiments confirmed the contribution of the TetA variant (S251A to tigecycline resistance. The transfer capacity of tigecycline resistance via this mutation was confirmed by conjugation experiments. Using southern blot hybridization and PCR assays, we further proved that the tetA gene was located on a transferable plasmid of ca. 65 kb in an Escherichia coli EC600 transconjugant. Our results provide direct in vivo evidence that evolution in the tetA gene can lead to tigecycline treatment failure in CRKP clinical strains that carry tetA. Moreover, the transfer capacity of tigecycline resistance mediated by mutated tetA is a threat.

  5. In vivo verification of superficial dose for head and neck treatments using intensity-modulated techniques

    International Nuclear Information System (INIS)

    Qi Zhenyu; Deng Xiaowu; Huang Shaomin; Zhang Li; He Zhichun; Allen Li, X.; Kwan, Ian; Lerch, Michael; Cutajar, Dean; Metcalfe, Peter; Rosenfeld, Anatoly

    2009-01-01

    Skin dose is one of the key issues for clinical dosimetry in radiation therapy. Currently planning computer systems are unable to accurately predict dose in the buildup region, leaving ambiguity as to the dose levels actually received by the patient's skin during radiotherapy. This is one of the prime reasons why in vivo measurements are necessary to estimate the dose in the buildup region. A newly developed metal-oxide-semiconductor-field-effect-transistor (MOSFET) detector designed specifically for dose measurements in rapidly changing dose gradients was introduced for accurate in vivo skin dosimetry. The feasibility of this detector for skin dose measurements was verified in comparison with plane parallel ionization chamber and radiochromic films. The accuracy of a commercial treatment planning system (TPS) in skin dose calculations for intensity-modulated radiation therapy treatment of nasopharyngeal carcinoma was evaluated using MOSFET detectors in an anthropomorphic phantom as well as on the patients. Results show that this newly developed MOSFET detector can provide a minimal but highly reproducible intrinsic buildup of 7 mg cm -2 corresponding to the requirements of personal surface dose equivalent Hp (0.07). The reproducibility of the MOSFET response, in high sensitivity mode, is found to be better than 2% at the phantom surface for the doses normally delivered to the patients. The MOSFET detector agrees well with the Attix chamber and the EBT Gafchromic registered film in terms of surface and buildup region dose measurements, even for oblique incident beams. While the dose difference between MOSFET measurements and TPS calculations is within measurement uncertainty for the depths equal to or greater than 0.5 cm, an overestimation of up to 8.5% was found for the surface dose calculations in the anthropomorphic phantom study. In vivo skin dose measurements reveal that the dose difference between the MOSFET results and the TPS calculations was on average -7

  6. Provisional crown failures in dental school predoctoral clinics.

    Science.gov (United States)

    Hyde, Jeffrey D; Bader, James A; Shugars, Daniel A

    2007-11-01

    Following a preliminary study indicating that at least 10 percent of single-unit crown temporary restorations failed in patients who received treatment by predoctoral students, a comprehensive examination of provisional crown failure was initiated to identify strategies to reduce the failure rate. For all provisionalized, natural tooth, single-unit crown preparations in University of North Carolina School of Dentistry predoctoral clinics for one year (N=1008), we noted tooth type, type of crown, student level, faculty coverage experience, treatment clinic, temporary material and luting agent, and retreatment (failure) of the provisional restoration. For failures, we also noted the stage of crown preparation at failure and the time since initial placement of the temporary. We analyzed these data using simple cross-tabs and logistic regression on need for retreatment (alpha =0.05). The failure rate was 18.75 percent (N=189). The median time to failure was twelve days; the 25(th) and 75(th) percentiles were six and twenty-six days. Significant risk factors, in order of odds ratio estimates, were molar tooth, second- or third-year student, and inexperienced faculty. Most provisional failures occurred during the final preparation phase of treatment. Provisional restoration failure is more frequent than was initially suspected from preliminary studies. Strategies for institutional intervention to reduce provisional restoration failure include greater attention to evaluating provisional crowns placed by inexperienced students (sophomores and juniors) and placing more emphasis on the retentiveness of provisional restorations reused following the final impression. Review of provisional evaluation procedures is also indicated for faculty who do not routinely supervise these procedures.

  7. Treatment of Experimental Brain Tumors with Trombospondin-1 Derived Peptides: an In Vivo Imaging Study

    Directory of Open Access Journals (Sweden)

    A. Bogdanov, Jr.

    1999-11-01

    Full Text Available Antiangiogenic and antiproliferative effects of synthetic D-reverse peptides derived from the type 1 repeats of thrombospondin (TSP1 [1,2] were studied in rodent C6 glioma and 9L gliosarcomas. To directly measure tumor size and vascular parameters, we employed in vivo magnetic resonance (MR imaging and corroborated results by traditional morphometric tissue analysis. Rats bearing either C6 or 9L tumors were treated with TSP1-derived peptide (D-reverse amKRFKQDGGWSHWSPWSSac, n=13 or a control peptide (D-reverse am KRAKQAGGASHASPASSac, n=12 at 10 mg/kg, administered either intravenously or through subcutaneous miniosmotic pumps starting 10 days after tumor implantation. Eleven days later, the effect of peptide treatment was evaluated. TSP1 peptide-treated 9L tumors (50.7±44.2 mm3, n=7 and C6 tumors (41.3±34.2 mm3, n=6 were significantly smaller than tumors treated with control peptide (9L: 215.7±67.8 mm3, n=6; C6:184.2±105.2 mm3, n=6. In contrast, the in vivo vascular volume fraction, the mean vascular area (determined by microscopy, and the microvascular density of tumors were not significantly different in any of the experimental groups. In cell culture, TSP1, and the amKRFKQDGGWSHWSPWSSac peptide showed antiproliferative effects against C6 with an IC of 45 nM for TSP1. These results indicate that TSP1derived peptides retard brain tumor growth presumably as a result of slower de novo blood vessel formation and synergistic direct antiproliferative effects on tumor cells. We also show that in vivo MR imaging can be used to assess treatment efficacy of novel antiangiogenic drugs non-invasively, which has obvious implications for clinical trials.

  8. Hemodilution after Initial Treatment in Patients with Acute Decompensated Heart Failure.

    Science.gov (United States)

    Fujita, Teppei; Inomata, Takayuki; Yazaki, Mayu; Iida, Yuichiro; Kaida, Toyoji; Ikeda, Yuki; Nabeta, Takeru; Ishii, Shunsuke; Maekawa, Emi; Yanagisawa, Tomoyoshi; Koitabashi, Toshimi; Takeuchi, Ichiro; Ako, Junya

    2018-05-09

    Decongestion is an important goal of heart failure (HF) management. Blood cell concentration is a recognized indicator for guiding decongestive treatment for HF. We aimed to assess the clinical impact of hemodilution and hemoconcentration after initial treatment in acute decompensated HF (ADHF) patients. We retrospectively evaluated hemoglobin levels and body weight obtained before admission, on admission, 3 days after admission, and at discharge in 102 consecutive patients admitted with ADHF. Patients were then stratified into hemodilution (n = 55) and hemoconcentration (n = 47) groups based on whether their hemoglobin levels decreased or increased, respectively, during the first 3 days after admission. From before admission to admission, hemoglobin levels decreased less in the hemodilution group (-0.16 ± 0.98 g/dL) than in the hemoconcentration group (-0.88 ± 1.11 g/dL) (P < 0.001); however, there was no significant difference in body weight (P≥ 0.05). More patients in the hemodilution group (85%) had grade III/IV pulmonary edema (Turner's criteria) compared with the hemoconcentration group (63%) (P < 0.01). Rate of readmission for HF within 180 days of discharge was higher in the hemodilution group (34%) compared with the hemoconcentration group (9%) (P < 0.01). Hemodilution after initial treatment for ADHF was associated with severe pulmonary edema at admission and higher readmission rates.

  9. Merit of Ginseng in the Treatment of Heart Failure in Type 1-Like Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Cheng-Chia Tsai

    2014-01-01

    Full Text Available The present study investigated the merit of ginseng in the improvement of heart failure in diabetic rats and the role of peroxisome proliferator-activated receptors δ (PPARδ. We used streptozotocin-induced diabetic rat (STZ-rat to screen the effects of ginseng on cardiac performance and PPARδ expression. Changes of body weight, water intake, and food intake were compared in three groups of age-matched rats; the normal control (Wistar rats received vehicle, STZ-rats received vehicle and ginseng-treated STZ-rats. We also determined cardiac performances in addition to blood glucose level in these animals. The protein levels of PPARδ in hearts were identified using Western blotting analysis. In STZ-rats, cardiac performances were decreased but the food intake, water intake, and blood glucose were higher than the vehicle-treated control. After a 7-day treatment of ginseng in STZ-rats, cardiac output was markedly enhanced without changes in diabetic parameters. This treatment with ginseng also increased the PPARδ expression in hearts of STZ-rats. The related signal of cardiac contractility, troponin I phosphorylation, was also raised. Ginseng-induced increasing of cardiac output was reversed by the cotreatment with PPARδ antagonist GSK0660. Thus, we suggest that ginseng could improve heart failure through the increased PPARδ expression in STZ-rats.

  10. Investigation of in vivo toxicity of hydroxylamine sulfate and the efficiency of intoxication treatment by α-tocopherol acetate and methylene blue.

    Science.gov (United States)

    Prodanchuk, Mykola G; Tsatsakis, Aristidis M; Prodanchuk, Georgiy M; Tsakalof, Andreas K

    2013-11-01

    Investigation of hydroxylamine sulfate toxicity mechanism in vivo and estimation of α-tocopherol acetate and methylene blue efficiency in poisoning treatments. In vivo experiments were conducted on 102 Wistar Han rats. The experiments investigated the hematotoxic and oxidative stress effects of hydroxylamine sulfate in acute and subacute toxicity treatment of animals. Electron Spin Resonance was used for quantitative determination of blood and liver tissue parameters alterations after intoxication. The osmotic fragility of erythrocytes, lipid peroxidation intensity and level of SH-groups in liver of rats were determined by established biochemical assays. Hydroxylamine sulfate cause an acute hematotoxicity and oxidative stress in vivo as demonstrated by the appearance of free oxidized iron in blood, reduced glutathione content and increased lipid peroxidation in liver. The experimental studies showed the formation of Hb-NO, MetHb in erythrocytes and as well of stable complex of reduced iron (Fe(2+)) with hydroxylamine sulfate. Methylene blue treatment does not reduce the Hb-NO or MetHb levels in intoxicated animals while administration of α-tocopherol acetate reduces substantially lipid peroxidation. Oxidative stress is a key mechanism of acute hematotoxicity caused by hydroxylamine sulfate. Methylene blue is not suitable antidote in case of hydroxylamine intoxication. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. What Is New in Heart Failure Management in 2017? Update on ACC/AHA Heart Failure Guidelines.

    Science.gov (United States)

    Bozkurt, Biykem

    2018-04-17

    The goal of this paper is to provide a summary of the new recommendations in the most recent 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. The intent is to provide the background and the supporting evidence for the recommendations and to provide practical guidance for management strategies in treatment of heart failure patients. In the 2017 ACC/AHA/HFSA Focused Update of HF guidelines, important additions include new information on biomarkers, specifically on the topics of the diagnostic, prognostic role of natriuretic peptides in heart failure, and the role of natriuretic peptides in screening in patients high risk for HF and prevention of HF. There are important recommendations for treatment of patients with HF with reduced EF (HFrEF), including the beneficial role of angiotensin receptor blocker and neprilysin inhibition (ARNI) treatment in reducing outcomes including mortality, ivabradine in reducing heart failure hospitalizations in stable HFrEF patients with sinus rhythm and heart rate ≥ 70 bpm despite β-blockers. In patients with HF with preserved EF (HFpEF), though there are no studies demonstrating survival benefit, potential benefit with aldosterone antagonism in reducing HF hospitalizations is noted. In treatment of comorbidities, optimization of blood pressure control to less than 130 mmHg is recommended in hypertensive patients to prevent HF or in patients with hypertension and HFrEF or HFpEF. In addition to recognition on the potential role of treatment of iron deficiency anemia to improve symptoms and functional capacity, caution against use of adaptive servo-ventilation in patients with HFrEF and central sleep apnea and against use of erythropoietin stimulating agents in patients with HFrEF is provided. There are new treatment

  12. Impact of cognitive function on compliance with treatment in heart failure

    Directory of Open Access Journals (Sweden)

    Beata Jankowska-Polańska

    2017-02-01

    Full Text Available In heart failure (HF patients frailty syndrome and cognitive impairment (CI affect outcome by decreasing the capability for performing self-care, adhering to the prescribed treatment regimen, monitoring symptoms. The aim was to investigate whether CI affects the compliance to therapeutic regimens. Methods: 170 with HF were included. We employed the Mini Mental State Examination (MMSE, for dementia and the Revised Heart Failure Compliance Scale to assess compliance. Results: CI patients showed lower compliance in all domains: 2.8±1.0 vs 3.3±1.0 (keeping appointments, 2.8±0.9 vs. 3.4±0.9 (pharmaceutical compliance, 0.4±0.8 vs. 1.4±1.2 (regular body weight monitoring, 2.0±1.3 vs. 2.7±1.0 (reduced salt intake, 1.9±1.2vs. 2.9±1.0 (fluid intake restriction, and 0.5±0.8 vs. 1.7±1.1 (regular exercise. Multiple regression analysis showed cognitive function to be an independent predictor for regular body weight monitoring (β=1.223;p<0.001, fluid intake restriction (β=1.081;p<0.001, and regular exercise (β=1.237;p<0.001. In multivariate analysis, the stimulant variables for compliance with HF treatment were: education (β=1.124, being in a relationship (β=2.231, and lack of cognitive impairment (β=0.320; the number of hospitalizations due to HF was identified as a destimulant (β=-0.495. Conclusion: Non-compliance is a major problem in elderly with HF. The cognitive function is an independent contributor to total compliance and to compliance with non-pharmaceutical recommendations. Being in a relationship and education are independent predictors of better compliance, while the number of rehospitalizations due to HF exacerbations is an independent predictor of worse compliance. Early detection of CI may offer an opportunity for intervention and a key strategy for improving clinical outcomes in older adults with HF.

  13. [Improvement in functional capacity after levothyroxine treatment in patients with chronic heart failure and subclinical hypothyroidism].

    Science.gov (United States)

    Curotto Grasiosi, Jorge; Peressotti, Bruno; Machado, Rogelio A; Filipini, Eduardo C; Angel, Adriana; Delgado, Jorge; Cortez Quiroga, Gustavo A; Rus Mansilla, Carmen; Martínez Quesada, María del Mar; Degregorio, Alejandro; Cordero, Diego J; Dak, Marcelo; Izurieta, Carlos; Esper, Ricardo J

    2013-10-01

    To assess whether levothyroxine treatment improves functional capacity in patients with chronic heart failure (New York Heart Association class i-iii) and subclinical hypothyroidism. One hundred and sixty-three outpatients with stable chronic heart failure followed up for at least 6 months were enrolled. A physical examination was performed, and laboratory tests including thyroid hormone levels, Doppler echocardiogram, radionuclide ventriculography, and Holter monitoring were requested. Functional capacity was assessed by of the 6-min walk test. Patients with subclinical hypothyroidism were detected and, after undergoing the s6-min walk test, were given replacement therapy. When they reached normal thyrotropin (TSH) levels, the 6-min walk test was performed again. The distance walked in both tests was recorded, and the difference in meters covered by each patient was analyzed. Prevalence of subclinical hypothyroidism in patients with heart failure was 13%. These patients walked 292±63m while they were hypothyroid and 350±76m when TSH levels returned to normal, a difference of 58±11m (P<.011). Patients with normal baseline TSH levels showed no significant difference between the 2 6-min walk tests. Patients with chronic heart failure and subclinical hypothyroidism significantly improved their physical performance when normal TSH levels were reached. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  14. Severe right heart failure in a patient with Grave's disease.

    Science.gov (United States)

    Xenopoulos, N P; Braden, G A; Applegate, R J

    1996-11-01

    This brief report presents a patient with isolated right heart failure and two rare underlying causes, hyperthyroidism and dysplastic tricuspid valve. Repair of the tricuspid valve and treatment of the hyperthyroidism were both essential for successful treatment of the right heart failure. Most important, recrudescence of hyperthyroidism in this patient was associated with reappearance of florid right heart failure. This report provides further information about a potential linkage of hyperthyroidism and severe right heart failure.

  15. Predictors of treatment failure in young patients undergoing in vitro fertilization.

    Science.gov (United States)

    Jacobs, Marni B; Klonoff-Cohen, Hillary; Agarwal, Sanjay; Kritz-Silverstein, Donna; Lindsay, Suzanne; Garzo, V Gabriel

    2016-08-01

    The purpose of the study was to evaluate whether routinely collected clinical factors can predict in vitro fertilization (IVF) failure among young, "good prognosis" patients predominantly with secondary infertility who are less than 35 years of age. Using de-identified clinic records, 414 women model predicted probability of cycle failure. One hundred ninety-seven patients with both primary and secondary infertility had a failed IVF cycle, and 217 with secondary infertility had a successful live birth. None of the women with primary infertility had a successful live birth. The significant predictors for IVF cycle failure among young patients were fewer previous live births, history of biochemical pregnancies or spontaneous abortions, lower baseline antral follicle count, higher total gonadotropin dose, unknown infertility diagnosis, and lack of at least one fair to good quality embryo. The full model showed good predictive value (c = 0.885) for estimating risk of cycle failure; at ≥80 % predicted probability of failure, sensitivity = 55.4 %, specificity = 97.5 %, positive predictive value = 95.4 %, and negative predictive value = 69.8 %. If this predictive model is validated in future studies, it could be beneficial for predicting IVF failure in good prognosis women under the age of 35 years.

  16. Numerical study and ex vivo assessment of HIFU treatment time reduction through optimization of focal point trajectory

    Science.gov (United States)

    Grisey, A.; Yon, S.; Pechoux, T.; Letort, V.; Lafitte, P.

    2017-03-01

    Treatment time reduction is a key issue to expand the use of high intensity focused ultrasound (HIFU) surgery, especially for benign pathologies. This study aims at quantitatively assessing the potential reduction of the treatment time arising from moving the focal point during long pulses. In this context, the optimization of the focal point trajectory is crucial to achieve a uniform thermal dose repartition and avoid boiling. At first, a numerical optimization algorithm was used to generate efficient trajectories. Thermal conduction was simulated in 3D with a finite difference code and damages to the tissue were modeled using the thermal dose formula. Given an initial trajectory, the thermal dose field was first computed, then, making use of Pontryagin's maximum principle, the trajectory was iteratively refined. Several initial trajectories were tested. Then, an ex vivo study was conducted in order to validate the efficicency of the resulting optimized strategies. Single pulses were performed at 3MHz on fresh veal liver samples with an Echopulse and the size of each unitary lesion was assessed by cutting each sample along three orthogonal planes and measuring the dimension of the whitened area based on photographs. We propose a promising approach to significantly shorten HIFU treatment time: the numerical optimization algorithm was shown to provide a reliable insight on trajectories that can improve treatment strategies. The model must now be improved in order to take in vivo conditions into account and extensively validated.

  17. GX1-conjugated poly(lactic acid nanoparticles encapsulating Endostar for improved in vivo anticolorectal cancer treatment

    Directory of Open Access Journals (Sweden)

    Du Y

    2015-05-01

    Full Text Available Yang Du,1,* Qian Zhang,1,* Lijia Jing,2 Xiaolong Liang,2 Chongwei Chi,1 Yaqian Li,1 Xin Yang,1 Zhifei Dai,2 Jie Tian1 1Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Department of Biomedical Engineering, College of Engineering, Peking University, Beijing People’s Republic of China *These authors contributed equally to this work Abstract: Tumor angiogenesis plays a key role in tumor growth and metastasis; thus, targeting tumor-associated angiogenesis is an important goal in cancer therapy. However, the efficient delivery of drugs to tumors remains a key issue in antiangiogenesis therapy. GX1, a peptide identified by phage-display technology, is a novel tumor vasculature endothelium-specific ligand and possesses great potential as a targeted vector and antiangiogenic agent in the diagnosis and treatment of human cancers. Endostar, a novel recombinant human endostatin, has been shown to inhibit tumor angiogenesis. In this study, we developed a theranostic agent composed of GX1-conjugated poly(lactic acid nanoparticles encapsulating Endostar (GPENs and labeled with the near-infrared dye IRDye 800CW to improve colorectal tumor targeting and treatment efficacy in vivo. The in vivo fluorescence molecular imaging data showed that GPENs (IRDye 800CW more specifically targeted tumors than free IRDye 800CW in colorectal tumor-bearing mice. Moreover, the antitumor efficacy was evaluated by bioluminescence imaging and immunohistology, revealing that GPENs possessed improved antitumor efficacy on subcutaneous colorectal xenografts compared to other treatment groups. Thus, our study showed that GPENs, a novel GX1 peptide guided form of nanoscale Endostar, can be used as a theranostic agent to facilitate more efficient targeted therapy and enable real-time monitoring of therapeutic efficacy in vivo

  18. Embryonic kidney function in a chronic renal failure model in rodents.

    Science.gov (United States)

    Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

    2017-08-01

    Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

  19. Heart Failure: From Research to Clinical Practice.

    Science.gov (United States)

    Islam, Md Shahidul

    2018-01-01

    "Heart failure: from research to clinical practice", a collection of selected reviews, which comes out also as a book, covers essentially all important aspects of heart failure, including the pathogenesis, clinical features, biomarkers, imaging techniques, medical treatment and surgical treatments, use of pacemakers and implantable cardioverter defibrillators, and palliative care. The reviews include essential background information, state of the art, critical and in-depth analysis, and directions for future researches for elucidation of the unresolved issues. Everyone interested in heart failure is expected to find this compilation helpful for a deeper understanding of some of the complex issues.

  20. Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo

    Directory of Open Access Journals (Sweden)

    Shengwei He

    2017-01-01

    Full Text Available Objective(s:To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo. Materials and Methods:Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor k-B ligan, and pre-collagen type 1 a were measured. Results:Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor k-B ligand, and pre-collagen type 1 a were also markedly higher following 25 and 50 Hz treatment. Conclusion:Low frequency (25–50 Hz vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury.

  1. SU-F-T-328: Real-Time in Vivo Dosimetry of Prostate SBRT Boost Treatments Using MOSkin Detectors

    International Nuclear Information System (INIS)

    Legge, K; O’Connor, D J; Cutajar, D; Rozenfeld, A; Wilfert, A; Martin, J; Greer, P

    2016-01-01

    Purpose: To provide in vivo measurements of dose to the anterior rectal wall during prostate SBRT boost treatments using MOSFET detectors. Methods: Dual MOSkin detectors were attached to a Rectafix rectal sparing device and inserted into patients during SBRT boost treatments. Patients received two boost fractions, each of 9.5–10 Gy and delivered using 2 VMAT arcs. Measurements were acquired for 12 patients. MOSFET voltages were read out at 1 Hz during delivery and converted to dose. MV images were acquired at known frequency during treatment so that the position of the gantry at each point in time was known. The cumulative dose at the MOSFET location was extracted from the treatment planning system at in 5.2° increments (FF beams) or at 5 points during each delivered arc (FFF beams). The MOSFET dose and planning system dose throughout the entirety of each arc were then compared using root mean square error normalised to the final planned dose for each arc. Results: The average difference between MOSFET measured and planning system doses determined over the entire course of treatment was 9.7% with a standard deviation of 3.6%. MOSFETs measured below the planned dose in 66% of arcs measured. Uncertainty in the position of the MOSFET detector and verification point are major sources of discrepancy, as the detector is placed in a high dose gradient region during treatment. Conclusion: MOSkin detectors were able to provide real time in vivo measurements of anterior rectal wall dose during prostate SBRT boost treatments. This method could be used to verify Rectafix positioning and treatment delivery. Further developments could enable this method to be used during high dose treatments to monitor dose to the rectal wall to ensure it remains at safe levels. Funding has been provided by the University of Newcastle. Kimberley Legge is the recipient of an Australian Postgraduate Award.

  2. SU-F-T-328: Real-Time in Vivo Dosimetry of Prostate SBRT Boost Treatments Using MOSkin Detectors

    Energy Technology Data Exchange (ETDEWEB)

    Legge, K; O’Connor, D J [University of Newcastle (Australia); Cutajar, D; Rozenfeld, A [University of Wollongong (Australia); Wilfert, A; Martin, J [Calvary Mater Newcastle (Australia); Greer, P [University of Newcastle (Australia); Calvary Mater Newcastle (Australia)

    2016-06-15

    Purpose: To provide in vivo measurements of dose to the anterior rectal wall during prostate SBRT boost treatments using MOSFET detectors. Methods: Dual MOSkin detectors were attached to a Rectafix rectal sparing device and inserted into patients during SBRT boost treatments. Patients received two boost fractions, each of 9.5–10 Gy and delivered using 2 VMAT arcs. Measurements were acquired for 12 patients. MOSFET voltages were read out at 1 Hz during delivery and converted to dose. MV images were acquired at known frequency during treatment so that the position of the gantry at each point in time was known. The cumulative dose at the MOSFET location was extracted from the treatment planning system at in 5.2° increments (FF beams) or at 5 points during each delivered arc (FFF beams). The MOSFET dose and planning system dose throughout the entirety of each arc were then compared using root mean square error normalised to the final planned dose for each arc. Results: The average difference between MOSFET measured and planning system doses determined over the entire course of treatment was 9.7% with a standard deviation of 3.6%. MOSFETs measured below the planned dose in 66% of arcs measured. Uncertainty in the position of the MOSFET detector and verification point are major sources of discrepancy, as the detector is placed in a high dose gradient region during treatment. Conclusion: MOSkin detectors were able to provide real time in vivo measurements of anterior rectal wall dose during prostate SBRT boost treatments. This method could be used to verify Rectafix positioning and treatment delivery. Further developments could enable this method to be used during high dose treatments to monitor dose to the rectal wall to ensure it remains at safe levels. Funding has been provided by the University of Newcastle. Kimberley Legge is the recipient of an Australian Postgraduate Award.

  3. SU-F-P-07: Applying Failure Modes and Effects Analysis to Treatment Planning System QA

    International Nuclear Information System (INIS)

    Mathew, D; Alaei, P

    2016-01-01

    Purpose: A small-scale implementation of Failure Modes and Effects Analysis (FMEA) for treatment planning system QA by utilizing methodology of AAPM TG-100 report. Methods: FMEA requires numerical values for severity (S), occurrence (O) and detectability (D) of each mode of failure. The product of these three values gives a risk priority number (RPN). We have implemented FMEA for the treatment planning system (TPS) QA for two clinics which use Pinnacle and Eclipse TPS. Quantitative monthly QA data dating back to 4 years for Pinnacle and 1 year for Eclipse have been used to determine values for severity (deviations from predetermined doses at points or volumes), and occurrence of such deviations. The TPS QA protocol includes a phantom containing solid water and lung- and bone-equivalent heterogeneities. Photon and electron plans have been evaluated in both systems. The dose values at multiple distinct points of interest (POI) within the solid water, lung, and bone-equivalent slabs, as well as mean doses to several volumes of interest (VOI), have been re-calculated monthly using the available algorithms. Results: The computed doses vary slightly month-over-month. There have been more significant deviations following software upgrades, especially if the upgrade involved re-modeling of the beams. TG-100 guidance and the data presented here suggest an occurrence (O) of 2 depending on the frequency of re-commissioning the beams, severity (S) of 3, and detectability (D) of 2, giving an RPN of 12. Conclusion: Computerized treatment planning systems could pose a risk due to dosimetric errors and suboptimal treatment plans. The FMEA analysis presented here suggests that TPS QA should immediately follow software upgrades, but does not need to be performed every month.

  4. SU-F-P-07: Applying Failure Modes and Effects Analysis to Treatment Planning System QA

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, D; Alaei, P [University Minnesota, Minneapolis, MN (United States)

    2016-06-15

    Purpose: A small-scale implementation of Failure Modes and Effects Analysis (FMEA) for treatment planning system QA by utilizing methodology of AAPM TG-100 report. Methods: FMEA requires numerical values for severity (S), occurrence (O) and detectability (D) of each mode of failure. The product of these three values gives a risk priority number (RPN). We have implemented FMEA for the treatment planning system (TPS) QA for two clinics which use Pinnacle and Eclipse TPS. Quantitative monthly QA data dating back to 4 years for Pinnacle and 1 year for Eclipse have been used to determine values for severity (deviations from predetermined doses at points or volumes), and occurrence of such deviations. The TPS QA protocol includes a phantom containing solid water and lung- and bone-equivalent heterogeneities. Photon and electron plans have been evaluated in both systems. The dose values at multiple distinct points of interest (POI) within the solid water, lung, and bone-equivalent slabs, as well as mean doses to several volumes of interest (VOI), have been re-calculated monthly using the available algorithms. Results: The computed doses vary slightly month-over-month. There have been more significant deviations following software upgrades, especially if the upgrade involved re-modeling of the beams. TG-100 guidance and the data presented here suggest an occurrence (O) of 2 depending on the frequency of re-commissioning the beams, severity (S) of 3, and detectability (D) of 2, giving an RPN of 12. Conclusion: Computerized treatment planning systems could pose a risk due to dosimetric errors and suboptimal treatment plans. The FMEA analysis presented here suggests that TPS QA should immediately follow software upgrades, but does not need to be performed every month.

  5. Ovarian failure in long-term survivors of childhood malignancy

    International Nuclear Information System (INIS)

    Stillman, R.J.; Schinfeld, J.S.; Schiff, I.; Gelber, R.D.; Greenberger, J.; Larson, M.; Jaffe, N.; Li, F.P.

    1981-01-01

    The frequency and causes of ovarian failure among 182 long-term survivors of childhood cancer were examined. Twenty-two patients (12%) had ovarian failure. Ovarian failure was found in 17 of 25 patients (68%) who had both ovaries within abdominal radiotherapy fields, in five of 35 patients (14%) whose ovaries were at the edge of the treatment field, and in none of 122 patients with one or both ovaries outside of an abdominal treatment field. Covariate and multivariate analyses of tumor type, age at diagnosis, duration of follow-up, abdominal tumor surgery, abdominal radiotherapy, number of chemotherapeutic agents administered, and cumulative doses of several drugs revealed that the location of the ovaries relative to radiation treatment fields was the only risk factor for subsequent ovarian failure

  6. Management of failure after surgery for gastro-esophageal reflux disease.

    Science.gov (United States)

    Gronnier, C; Degrandi, O; Collet, D

    2018-04-01

    Surgical treatment of gastro-esophageal reflux disease (ST-GERD) is well-codified and offers an alternative to long-term medical treatment with a better efficacy for short and long-term outcomes. However, failure of ST-GERD is observed in 2-20% of patients; management is challenging and not standardized. The aim of this study is to analyze the causes of failure and to provide a treatment algorithm. The clinical aspects of ST-GERD failure are variable including persistent reflux, dysphagia or permanent discomfort leading to an important degradation of the quality of life. A morphological and functional pre-therapeutic evaluation is necessary to: (i) determine whether the symptoms are due to recurrence of reflux or to an error in initial indication and (ii) to understand the cause of the failure. The most frequent causes of failure of ST-GERD include errors in the initial indication, which often only need medical treatment, and surgical technical errors, for which surgical redo surgery can be difficult. Multidisciplinary management is necessary in order to offer the best-adapted treatment. Copyright © 2018. Published by Elsevier Masson SAS.

  7. Risk-Cost Estimation of On-Site Wastewater Treatment System Failures Using Extreme Value Analysis.

    Science.gov (United States)

    Kohler, Laura E; Silverstein, JoAnn; Rajagopalan, Balaji

    2017-05-01

      Owner resistance to increasing regulation of on-site wastewater treatment systems (OWTS), including obligatory inspections and upgrades, moratoriums and cease-and-desist orders in communities around the U.S. demonstrate the challenges associated with managing risks of inadequate performance of owner-operated wastewater treatment systems. As a result, determining appropriate and enforceable performance measures in an industry with little history of these requirements is challenging. To better support such measures, we develop a statistical method to predict lifetime failure risks, expressed as costs, in order to identify operational factors associated with costly repairs and replacement. A binomial logistic regression is used to fit data from public records of reported OWTS failures, in Boulder County, Colorado, which has 14 300 OWTS to determine the probability that an OWTS will be in a low- or high-risk category for lifetime repair and replacement costs. High-performing or low risk OWTS with repairs and replacements below the threshold of $9000 over a 40-year life are associated with more frequent inspections and upgrades following home additions. OWTS with a high risk of exceeding the repair cost threshold of $18 000 are further analyzed in a variation of extreme value analysis (EVA), Points Over Threshold (POT) where the distribution of risk-cost exceedance values are represented by a generalized Pareto distribution. The resulting threshold cost exceedance estimates for OWTS in the high-risk category over a 40-year expected life ranged from $18 000 to $44 000.

  8. Development of an electronic medical record based alert for risk of HIV treatment failure in a low-resource setting.

    Directory of Open Access Journals (Sweden)

    Nancy Puttkammer

    Full Text Available The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients' adherence to HIV antiretroviral therapy (ART and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk.Among adult patients enrolled on ART from 2005-2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6-12 months on treatment, based on the World Health Organization's immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves.Among 923 patients with CD4 results available during the period 6-12 months after ART initiation, 196 (21.2% met ART failure criteria. The pharmacy-based proportion of days covered (PDC measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (p<0.01. When additional information including sex, baseline CD4, and duration of enrollment in HIV care prior to ART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation.Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs.

  9. Outcomes of changing immunosuppressive therapy after treatment failure in patients with noninfectious uveitis.

    Science.gov (United States)

    Joshi, Lavnish; Talat, Lazha; Yaganti, Satish; Sandhu, Sartaj; Taylor, Simon R J; Wakefield, Denis; McCluskey, Peter; Lightman, Susan

    2014-05-01

    To evaluate the outcomes of changing immunosuppressive therapy for noninfectious uveitis after failure. Retrospective cohort study. Patients with noninfectious uveitis managed at 2 tertiary uveitis clinics in the United Kingdom and Australia. Participants with a history of using immunosuppressive therapy were identified in clinics, and notes were reviewed by doctors trained in uveitis therapy. Each treatment episode/course (starting or changing a therapy) was identified, and demographic details, clinical characteristics, drug used (second-line immunosuppressive agent [ISA] or biologicals), and drug doses were obtained. For each treatment episode, the reasons for changing therapy, corticosteroid-sparing effects, and control of inflammation were determined. A total of 147 patients were identified who underwent 309 different treatment episodes. Fifty-five percent of patients eventually required a change in treatment after their first treatment episode/course. Forty-five episodes involved switching from one ISA to another, with 50% to 100% of these patients achieving "success" (prednisolone ≤10 mg and sustained control) with the new ISA. A combination of ISAs were used in 53 episodes, with "success" being achieved in 50% to 71% of these patients. Biological agents were used in 45 episodes, the most common one being infliximab, which achieved success in 80% of patients. Our data suggest that control of inflammation can be achieved after switching or combining ISAs. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  10. The in vivo biofilm

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Maria; Alhede, Morten

    2013-01-01

    Bacteria can grow and proliferate either as single, independent cells or organized in aggregates commonly referred to as biofilms. When bacteria succeed in forming a biofilm within the human host, the infection often becomes very resistant to treatment and can develop into a chronic state. Biofilms...... have been studied for decades using various in vitro models, but it remains debatable whether such in vitro biofilms actually resemble in vivo biofilms in chronic infections. In vivo biofilms share several structural characteristics that differ from most in vitro biofilms. Additionally, the in vivo...... experimental time span and presence of host defenses differ from chronic infections and the chemical microenvironment of both in vivo and in vitro biofilms is seldom taken into account. In this review, we discuss why the current in vitro models of biofilms might be limited for describing infectious biofilms...

  11. Second date appendectomy: Operating for failure of nonoperative treatment in perforated appendicitis.

    Science.gov (United States)

    Lotti, Marco

    2017-06-01

    Nonoperative treatment of acute appendicitis is embraced by many surgical teams, driven by low to moderate quality randomized studies that support noninferiority of antibiotics versus appendectomy for treatment of acute uncomplicated appendicitis. Several flaws of these studies have emerged, especially in the recruitment strategy and in the diagnostic criteria that were used. The growing confidence given to antibiotics, together with the lack of reliable criteria to distinguish between uncomplicated and perforated appendicitis, exposes patients with perforated appendicitis to the likelihood to be treated with antibiotics instead of surgery. Among them, those patients who experience a temporary relief of symptoms due to antibiotics, followed by early recurrence of disease when antibiotics are discontinued, are likely to undergo appendectomy at their second date. Second date appendectomy, i.e. the removal of the appendix when acute inflammation relapses within the scar of a previously unhealed perforated appendicitis, is the unwanted child of the nonoperative treatment and a new challenge for both the surgeon and the patient. Between June and July 2016, two patients were readmitted and operated for failure of nonoperative treatment with antibiotics. A video is presented, which focuses on the different anatomic presentation and technical challenges between prompt and second date laparoscopic appendectomy. When proposing nonoperative treatment for acute appendicitis, surgeons should be aware and inform their patients that if the appendix is perforated and an incomplete healing and early recurrence occur, a second date appendectomy could be a more challenging operation compared to a prompt appendectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Increased treatment failure after 3-days’ courses of nitrofurantoin and trimethoprim for urinary tract infections in women: a population-based retrospective cohort study using the PHARMO database

    Science.gov (United States)

    Goettsch, Wim G; Janknegt, Rob; Herings, Ron M C

    2004-01-01

    Aim To assess determinants of treatment failure after antimicrobial therapy of urinary tract infections in women. Methods In primary care 16 703 Dutch women who received a first course (3, 5 or 7 days) of trimethoprim, nitrofurantoin or norfloxacin between 1 January 1992 through 31 December 1997 and who were between 15 and 65 years old at the day of first use were selected. Failure of the initial treatment was defined as a further prescription for one of these three antibiotics or for cotrimoxazole, amoxicillin, ciprofloxacin or ofloxacin, within 31 days after the end of the initial therapy. Results Treatment failure rate was 14.4% in patients treated with trimethoprim and nitrofurantoin and 9.6% in patients treated with norfloxacin. A multivariate analysis showed that 5 days’[RRNIT 0.67, 95% confidence interval (CI) 0.57, 0.82, RRTRI 0.82, 95% CI 0.73, 0.91] and 7 days’ (RRNIT 0.64, 95% CI 0.53, 0.77, RRTRI 0.85, 95% CI 0.71, 1.02) trimethoprim and nitrofurantoin treatment appeared to be more effective than a 3-day treatment (reference category). Other factors increasing treatment failure rates were the age of the patient, the year of therapy and previous hospitalization. Conclusions It may be concluded that 3-day courses of nitrofurantoin and trimethoprim are less effective than 5- and 7-day courses in the treatment of uncomplicated urinary tract infections in women. PMID:15255801

  13. [Complications and failures in dentoalveolar surgery

    NARCIS (Netherlands)

    Stoelinga, P.J.W.

    2009-01-01

    Complications and failures are unavoidable in dentoalveolar surgery, but can be reduced if treatment is carried out in the proper manner. Yet, one has to accept a certain percentage of complications and failures and the patient should be informed about that prior to surgery. Complications become

  14. Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya.

    Science.gov (United States)

    Brooks, Katherine; Diero, Lameck; DeLong, Allison; Balamane, Maya; Reitsma, Marissa; Kemboi, Emmanuel; Orido, Millicent; Emonyi, Wilfred; Coetzer, Mia; Hogan, Joseph; Kantor, Rami

    2016-01-01

    Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya. We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients' characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests. Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations. In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for

  15. Frequency of enterococcus faecalis in saliva and root canals with treatment failure

    International Nuclear Information System (INIS)

    Khan, I.; Shan, T.; Manzoor, M.A.

    2015-01-01

    To compare the frequency of E. faecalis in the saliva and root canals of teeth associated with apical periodontitis due to endodontic treatment failure in the same patient. Study Design: Cross-sectional comparative study. Place and Duration of Study: Samples were collected from Operative Dentistry Department, AFID, while laboratory processing was done at AFIP, Rawalpindi. Study duration was one year. Patients and Methods: Fifty patients, both males and females with failed endodontic treatment were selected. Saliva and root canal samples were collected from each patient, inoculated on MacKonkey agar plate and incubated at 35-37 degree C for 48 hrs. E. faecalis colonies were identified by colony morphology, gramstain, catalase, bile asculin test, arabinose fermentation and growth in 6% NaCl nutrient broth. Results: The frequency of E. faecalis in saliva was 34% and in root canal it was 58%. Frequency between the presence of E. faecalis in root canals and saliva was found to be statistically different (p = 0.001). Conclusion: The presence of E. faecalis in root canal was not associated with their presence in saliva. (author)

  16. Frequency of enterococcus faecalis in saliva and root canals with treatment failure

    International Nuclear Information System (INIS)

    Shan, T.; Manzoor, M.A.; Hussain, W.

    2014-01-01

    To compare the frequency of E.faecalis in the saliva and root canals of teeth associated with apical periodontitis due to endodontic treatment failure Study. Design: Cross-sectional comparative. Place and Duration of Study: Samples were collected from Operative Dentistry department, AFID, while laboratory processing was done at AFIP, Rawalpindi. Duration of this study was one year. Patients and Method: Fifty patients, both males and females with failed endodontic treatment were selected. Saliva and root canal samples were collected from each patient, inoculated on MacKonkey agar plate and incubated at 35-370 C for 48 hours. E.faecalis colonies were identified by colony morphology, Gram stain, catalase, bile asculin test, arabinose fermentation and growth in 6% NaCl nutrient broth. Results: The frequency of E.faecalis in saliva was 34% and 58% in root canal samples. Frequency of the presence of E.faecalis in root canals and saliva was found to be statistically different (p=0.000). Conclusion: The presence of E.faecalis in root canal was not associated with their presence in saliva. (author)

  17. Strength and failure analysis of composite-to-composite adhesive bonds with different surface treatments

    Science.gov (United States)

    Paranjpe, Nikhil; Alamir, Mohammed; Alonayni, Abdullah; Asmatulu, Eylem; Rahman, Muhammad M.; Asmatulu, Ramazan

    2018-03-01

    Adhesives are widely utilized materials in aviation, automotive, energy, defense, and marine industries. Adhesive joints are gradually supplanting mechanical fasteners because they are lightweight structures, thus making the assembly lighter and easier. They also act as a sealant to prevent a structural joint from galvanic corrosion and leakages. Adhesive bonds provide high joint strength because of the fact that the load is distributed uniformly on the joint surface, while in mechanical joints, the load is concentrated at one point, thus leading to stress at that point and in turn causing joint failures. This research concentrated on the analysis of bond strength and failure loads in adhesive joint of composite-to-composite surfaces. Different durations of plasma along with the detergent cleaning were conducted on the composite surfaces prior to the adhesive applications and curing processes. The joint strength of the composites increased about 34% when the surface was plasma treated for 12 minutes. It is concluded that the combination of different surface preparations, rather than only one type of surface treatment, provides an ideal joint quality for the composites.

  18. Operative shortening of the sling as a second-line treatment after TVT failure

    Science.gov (United States)

    Matuszewski, Marcin; Michajłowski, Jerzy; Krajka, Kazimierz

    2011-01-01

    Introduction Stress urinary incontinence (SUI) is defined as an involuntary loss of urine during physical exertion, sneezing, coughing, laughing, or other activities that put pressure on the bladder. In some cases, recurrent or persistent SUI after sling operations may be caused by too loose placement of the sling. In the current study, we describe our method of shortening of the sling as a second-line treatment of tension-free vaginal tape (TVT) failure. Materials and methods Four women, aged 46-61, after initial TVT operation were treated for persistent SUI. The severity of SUI was estimated by: physical examinations, cough tests, 24-h pad tests, and King's Health Questionnaire. The shortening procedure, based on excising the fragment of tape and suturing it back, was performed in all patients. Results All cases achieved a good result, which was defined as restoration of full continence. No complications occurred. The 12-month follow-up showed no side-effects. The postoperative control tests: the cough and 24-h pad tests were negative in all women. The general health perceptions increased after the shortening procedure by a mean value 44.25%. The incontinence impact decreased by a mean value 44.6%. In all patients, role and physical limitations significantly decreased (by 88.5% and 80.5%, respectively). The negative emotions connected with SUI significantly decreased after the second procedure. Conclusions The operative shortening of the implanted sling is a simple, cheap, and effective method of second-line treatment in cases of TVT failure and may be offered to the majority of patients with insufficient urethral support after the first procedure. PMID:24578885

  19. Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient meta-analysis

    NARCIS (Netherlands)

    Troughton, Richard W.; Frampton, Christopher M.; Brunner-La Rocca, Hans-Peter; Pfisterer, Matthias; Eurlings, Luc W. M.; Erntell, Hans; Persson, Hans; O'Connor, Christopher M.; Moertl, Deddo; Karlström, Patric; Dahlström, Ulf; Gaggin, Hanna K.; Januzzi, James L.; Berger, Rudolf; Richards, A. Mark; Pinto, Yigal M.; Nicholls, M. Gary

    2014-01-01

    Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of

  20. In vivo dosimetry in radiation therapy in Sweden

    International Nuclear Information System (INIS)

    Eriksson, Jacob; Blomquist, Michael

    2010-07-01

    A prerequisite for achieving high radiation safety for patients receiving external beam radiation therapy is that the hospitals have a quality assurance program. The program should include include monitoring of the radiation dose given to the patient. Control measurements are performed both at the system level and at the individual level. Control measurement is normally performed using in vivo dosimetry, e.g. a method to measure the radiation dose at the individual level during the actual radiation treatment time. In vivo dosimetry has proven to be an important tool to detect and prevent serious errors in patient treatment. The purpose of this research project was to identify the extent to which vivo dosimetry is used and the methods available for this at Swedish radiation therapy clinics. The authority also wanted to get an overall picture of how hospitals manage results of in vivo dosimetry, and how clinics control radiation dose when using modern treatment techniques. The report reflects the situation in Swedish radiotherapy clinics 2007. The report shows that all hospitals use some form of in vivo dosimetry. The instruments used are mainly diodes and termoluminiscence dosimeters

  1. Use of Inotropic Agents in Treatment of Systolic Heart Failure

    Directory of Open Access Journals (Sweden)

    Sohaib Tariq

    2015-12-01

    Full Text Available The most common use of inotropes is among hospitalized patients with acute decompensated heart failure, with reduced left ventricular ejection fraction and with signs of end-organ dysfunction in the setting of a low cardiac output. Inotropes can be used in patients with severe systolic heart failure awaiting heart transplant to maintain hemodynamic stability or as a bridge to decision. In cases where patients are unable to be weaned off inotropes, these agents can be used until a definite or escalated supportive therapy is planned, which can include coronary revascularization or mechanical circulatory support (intra-aortic balloon pump, extracorporeal membrane oxygenation, impella, left ventricular assist device, etc.. Use of inotropic drugs is associated with risks and adverse events. This review will discuss the use of the inotropes digoxin, dopamine, dobutamine, norepinephrine, milrinone, levosimendan, and omecamtiv mecarbil. Long-term inotropic therapy should be offered in selected patients. A detailed conversation with the patient and family shall be held, including a discussion on the risks and benefits of use of inotropes. Chronic heart failure patients awaiting heart transplants are candidates for intravenous inotropic support until the donor heart becomes available. This helps to maintain hemodynamic stability and keep the fluid status and pulmonary pressures optimized prior to the surgery. On the other hand, in patients with severe heart failure who are not candidates for advanced heart failure therapies, such as transplant and mechanical circulatory support, inotropic agents can be used for palliative therapy. Inotropes can help reduce frequency of hospitalizations and improve symptoms in these patients.

  2. Use of Inotropic Agents in Treatment of Systolic Heart Failure.

    Science.gov (United States)

    Tariq, Sohaib; Aronow, Wilbert S

    2015-12-04

    The most common use of inotropes is among hospitalized patients with acute decompensated heart failure, with reduced left ventricular ejection fraction and with signs of end-organ dysfunction in the setting of a low cardiac output. Inotropes can be used in patients with severe systolic heart failure awaiting heart transplant to maintain hemodynamic stability or as a bridge to decision. In cases where patients are unable to be weaned off inotropes, these agents can be used until a definite or escalated supportive therapy is planned, which can include coronary revascularization or mechanical circulatory support (intra-aortic balloon pump, extracorporeal membrane oxygenation, impella, left ventricular assist device, etc.). Use of inotropic drugs is associated with risks and adverse events. This review will discuss the use of the inotropes digoxin, dopamine, dobutamine, norepinephrine, milrinone, levosimendan, and omecamtiv mecarbil. Long-term inotropic therapy should be offered in selected patients. A detailed conversation with the patient and family shall be held, including a discussion on the risks and benefits of use of inotropes. Chronic heart failure patients awaiting heart transplants are candidates for intravenous inotropic support until the donor heart becomes available. This helps to maintain hemodynamic stability and keep the fluid status and pulmonary pressures optimized prior to the surgery. On the other hand, in patients with severe heart failure who are not candidates for advanced heart failure therapies, such as transplant and mechanical circulatory support, inotropic agents can be used for palliative therapy. Inotropes can help reduce frequency of hospitalizations and improve symptoms in these patients.

  3. Proportion of Patients Reporting Acceptable Symptoms or Treatment Failure and Their Associated KOOS Values at 6 to 24 Months After Anterior Cruciate Ligament Reconstruction

    DEFF Research Database (Denmark)

    Ingelsrud, Lina Holm; Granan, Lars-Petter; Terwee, Caroline B

    2015-01-01

    -34) to 71 (95% CI, 65-76) for patients with treatment failure. For both categories, the worst subscale values were seen in the sport and recreation and quality of life subscales and the best in the activities of daily living subscale. CONCLUSION: Only half of the patients at 6 months and about two......-thirds at 1 to 2 years perceived their symptoms as acceptable after ACLR. For these patients, KOOS values reflected no problems to mild problems on average, while for patients reporting treatment failure, KOOS values reflected moderate to severe problems....

  4. Geographic differences in heart failure trials.

    Science.gov (United States)

    Ferreira, João Pedro; Girerd, Nicolas; Rossignol, Patrick; Zannad, Faiez

    2015-09-01

    Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial-specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF-PEF), heart failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF-PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

  5. Comparison of in-vivo failure of single-thread and dual-thread temporary anchorage devices over 18 months: A split-mouth randomized controlled trial.

    Science.gov (United States)

    Durrani, Owais Khalid; Shaheed, Sohrab; Khan, Arsalan; Bashir, Ulfat

    2017-10-01

    The purpose of this study was to compare the in-vivo failure rates of single-thread and dual-thread temporary anchorage device (TAD) designs over 18 months. Thirty patients with skeletal Class II Division 1 malocclusion requiring anchorage from TADs for retraction of maxillary incisors into the extracted premolar space were recruited in this parallel group, split-mouth, randomized controlled trial. A block randomization sequence was generated with Random Allocation Software (version 2.0; Isfahan, Iran) with the allocations concealed in sequentially numbered, opaque, sealed envelopes. A total of 60 TADs (diameter, 2 mm; length, 10 mm) were placed in the maxillary arches of these patients with random allocation of the 2 types to the left and the right sides in a 1:1 ratio. All TADs were placed between the roots of the second premolar and the first molar and were immediately loaded. Patients were followed for a minimum of 12 months and a maximum of 18 months for the failure of the TADs. Data were analyzed blindly on an intention-to-treat basis. Four TADs (13.3%) failed in the single-thread group, and 6 TADs (20%) failed in the dual-thread group. The McNemar test showed an insignificant difference (P = 0.72) between the 2 groups. An odds ratio of 1.6 (95% confidence interval, 0.39-6.97) showed no significant associations among the variables. Most TADs failed in the first month after insertion (50%). The failure rate of dual-thread TADs compared with single-thread TADs is statistically insignificant when placed in the maxilla for retraction of the anterior segment. Registration: The trial was not registered before commencement. The protocol was not published before the trial. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  6. Trunnion Failure of the Recalled Low Friction Ion Treatment Cobalt Chromium Alloy Femoral Head.

    Science.gov (United States)

    Urish, Kenneth L; Hamlin, Brian R; Plakseychuk, Anton Y; Levison, Timothy J; Higgs, Genymphas B; Kurtz, Steven M; DiGioia, Anthony M

    2017-09-01

    Gross trunnion failure (GTF) is a rare complication in total hip arthroplasty (THA) reported across a range of manufacturers. Specific lots of the Stryker low friction ion treatment (LFIT) anatomic cobalt chromium alloy (CoCr) V40 femoral head were recalled in August 2016. In part, the recall was based out of concerns for disassociation of the femoral head from the stem and GTF. We report on 28 patients (30 implants) with either GTF (n = 18) or head-neck taper corrosion (n = 12) of the LFIT CoCr femoral head and the Accolade titanium-molybdenum-zirconium-iron alloy femoral stems. All these cases were associated with adverse local tissue reactions requiring revision of the THA. In our series, a conservative estimate of the incidence of failure was 4.7% (n = 636 total implanted) at 8.0 ± 1.4 years from the index procedure. Failures were associated with a high-offset 127° femoral stem neck angle and increased neck lengths; 43.3% (13 of 30) of the observed failures included implant sizes outside the voluntary recall (27.8% [5 of 18] of the GTF and 75.0% [8 of 12] of the taper corrosion cases). Serum cobalt and chromium levels were elevated (cobalt: 8.4 ± 7.0 μg/mL; chromium: 3.4 ± 3.3 μ/L; cobalt/chromium ratio: 3.7). The metal artifact reduction sequence magnetic resonance imaging demonstrated large cystic fluid collections typical with adverse local tissue reactions. During revision, a pseudotumor was observed in all cases. Pathology suggested a chronic inflammatory response. Impending GTF could be diagnosed based on aspiration of black synovial fluid and an oblique femoral head as compared with the neck taper on radiographs. In our series of the recalled LFIT CoCr femoral head, the risk of impending GTF or head-neck taper corrosion should be considered as a potential diagnosis in a painful LFIT femoral head and Accolade titanium-molybdenum-zirconium-iron alloy THA with unknown etiology. Almost half of the failures we observed included sizes outside of the

  7. In vivo photoacoustic monitoring of anti-obesity photothermal lipolysis

    Science.gov (United States)

    Lee, Donghyun; Lee, Jung Ho; Hahn, Sei Kwang; Kim, Chulhong

    2018-02-01

    Obesity with a body mass index is greater than 30 kg/m2 is one of the rapidly growing diseases in advanced societies and can lead to stroke, type 2 diabetes, and heart failure. Common methods of removing subcutaneous adipose tissues are liposuction and laser treatment. In this study, we used photoacoustic imaging to monitor the anti-obesity photothermal degradation process. To improve the photothermal lipid degradation efficiency without any invasive methods, we synthesized hyaluronic acid hollow hold nanosphere adipocyte targeting sequence peptide (HA-HAuNS-ATS) conjugates. The conjugate enhanced the skin penetration ability and biodegradability of the nanoparticles using hyaluronate and enhanced the targeting effect on adipose tissue with adipocyte targeting sequence peptide. Thus, the conjugate can be delivered to the adipose tissue by simply spreading the conjugate on the skin without any invasive method. Then, the photothermal lipolysis and delivery of the conjugate were photoacoustically monitored in vivo. These results demonstrate the potential for photoacoustic method to be applied for photothermal lipolysis monitoring.

  8. Failure to achieve immunological recovery in HIV-infected patients with clinical and virological success after 10 years of combined ART: role of treatment course.

    Science.gov (United States)

    Raffi, François; Le Moing, Vincent; Assuied, Alex; Habak, Sofiane; Spire, Bruno; Cazanave, Charles; Billaud, Eric; Dellamonica, Pierre; Ferry, Tristan; Fagard, Catherine; Leport, Catherine

    2017-01-01

    We assessed factors, including treatment course, associated with failure to obtain a 10 year immunological response after starting first-generation PI-containing combined ART (cART). In the prospective COPILOTE cohort of HIV-infected patients started on a first-generation PI-containing regimen in 1997-99, the impact of cART history on the failure to achieve immunological response measured at 10 years was assessed by multivariate logistic regression models in the 399 patients with clinical and virological success of cART. Failure of CD4 response (CD4 >500/mm 3 ) was associated with age ≥40 years at baseline (P failure to achieve complete immunological response (CD4 >500/mm 3 and CD4:CD8 ratio >1) were CD4:CD8 ratio ≤0.8 at month 8 (P success. Lack of treatment interruption may improve long-term immunological outcome in HIV infection. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Virtual Reality Treatment in Acrophobia : A Comparison with Exposure in Vivo

    NARCIS (Netherlands)

    Emmelkamp, P.M.G.; Bruynzeel, M.; Drost, L.; Van der Mast, C.A.P.G.

    2001-01-01

    The aim of the present study was to evaluate the effectiveness of low-budget virtual reality exposure versus exposure in vivo in a within-group design in 10 individuals suffering from acrophobia. Virtual reality exposure was found to be at least as effective as exposure in vivo on anxiety and

  10. Monitoring the efficacy of antimalarial medicines in India via sentinel sites: Outcomes and risk factors for treatment failure.

    Science.gov (United States)

    Mishra, Neelima; Srivastava, Bina; Bharti, Ram Suresh; Rana, Roma; Kaitholia, Kamlesh; Anvikar, Anupkumar R; Das, Manoj Kumar; Ghosh, Susanta K; Bhatt, Rajendra M; Tyagi, Prajesh K; Dev, Vas; Phookan, Sobhan; Wattal, Suman Lata; Sonal, Gagan Singh; Dhariwal, Akshay Chand; Valecha, Neena

    2016-01-01

    To combat the problem of antimalarial drug resistance, monitoring the changes in drug efficacy over time through periodic surveillance is essential. Since 2009, systematic and continuous monitoring is being done through nationwide sentinel site system. Potential early warning signs like partner drug resistance markers were also monitored in the clinical samples from the study areas. A total of 1864 patients with acute uncomplicated malaria were enrolled in therapeutic efficacy studies of artesunate plus sulphadoxine-pyrimethamine (AS+SP) for Plasmodium falciparum; those infected with P. vivax were given chloroquine (CQ). Polymerase chain reaction (PCR) was used to distinguish post-treatment reinfection from treatment failures. Isolates of P. falciparum were also analysed for dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) gene mutations. Overall, 1687 (91.7%) patients completed the follow-up. In most of the falciparum patients the parasitaemia was cleared within 24 h of treatment, except 12 patients who remained parasite positive after 72 h. Presence of dhfr and dhps quintuple mutation was observed predominantly in treatment failure samples. A daily dose of artesunate of 95% cases in all the sentinel sites except in Northeastern region (NE). Chloroquine remained 100% efficacious in case of P. vivax infections. Till 2012, India's national antimalarial drug resistance monitoring system proved highly efficacious and safe towards first-line antimalarials used in the country, except in Northeastern region where a decline in efficacy of AS+SP has been observed. This led to change in first-line treatment for P. falciparum to artemether-lumefantrine in Northeastern region.

  11. Iron deficiency and anemia in heart failure.

    Science.gov (United States)

    Çavuşoğlu, Yüksel; Altay, Hakan; Çetiner, Mustafa; Güvenç, Tolga Sinan; Temizhan, Ahmet; Ural, Dilek; Yeşilbursa, Dilek; Yıldırım, Nesligül; Yılmaz, Mehmet Birhan

    2017-03-01

    Heart failure is an important community health problem. Prevalence and incidence of heart failure have continued to rise over the years. Despite recent advances in heart failure therapy, prognosis is still poor, rehospitalization rate is very high, and quality of life is worse. Co-morbidities in heart failure have negative impact on clinical course of the disease, further impair prognosis, and add difficulties to treatment of clinical picture. Therefore, successful management of co-morbidities is strongly recommended in addition to conventional therapy for heart failure. One of the most common co-morbidities in heart failure is presence of iron deficiency and anemia. Current evidence suggests that iron deficiency and anemia are more prevalent in patients with heart failure and reduced ejection fraction, as well as those with heart failure and preserved ejection fraction. Moreover, iron deficiency and anemia are referred to as independent predictors for poor prognosis in heart failure. There is strong relationship between iron deficiency or anemia and severity of clinical status of heart failure. Over the last two decades, many clinical investigations have been conducted on clinical effectiveness of treatment of iron deficiency or anemia with oral iron, intravenous iron, and erythropoietin therapies. Studies with oral iron and erythropoietin therapies did not provide any clinical benefit and, in fact, these therapies have been shown to be associated with increase in adverse clinical outcomes. However, clinical trials in patients with iron deficiency in the presence or absence of anemia have demonstrated considerable clinical benefits of intravenous iron therapy, and based on these positive outcomes, iron deficiency has become target of therapy in management of heart failure. The present report assesses current approaches to iron deficiency and anemia in heart failure in light of recent evidence.

  12. Capacity for diagnosis and treatment of heart failure in sub-Saharan Africa.

    Science.gov (United States)

    Carlson, Selma; Duber, Herbert C; Achan, Jane; Ikilezi, Gloria; Mokdad, Ali H; Stergachis, Andy; Wollum, Alexandra; Bukhman, Gene; Roth, Gregory A

    2017-12-01

    Heart failure is a major cause of disease burden in sub-Saharan Africa (SSA). There is an urgent need for better strategies for heart failure management in this region. However, there is little information on the capacity to diagnose and treat heart failure in SSA. We aim to provide a better understanding of the capacity to diagnose and treat heart failure in Kenya and Uganda to inform policy planning and interventions. We analysed data from a nationally representative survey of health facilities in Kenya and Uganda (197 health facilities in Uganda and 143 in Kenya). We report on the availability of cardiac diagnostic technologies and select medications for heart failure (β-blockers, ACE inhibitors and furosemide). Facility-level data were analysed by country and platform type (hospital vs ambulatory facilities). Functional and staffed radiography, ultrasound and ECG were available in less than half of hospitals in Kenya and Uganda combined. Of the hospitals surveyed, 49% of Kenyan and 77% of Ugandan hospitals reported availability of the heart failure medication package. ACE inhibitors were only available in 51% of Kenyan and 79% of Ugandan hospitals. Almost one-third of the hospitals in each country had a stock-out of at least one of the medication classes in the prior quarter. Few facilities in Kenya and Uganda were prepared to diagnose and manage heart failure. Medication shortages and stock-outs were common. Our findings call for increased investment in cardiac care to reduce the growing burden of heart failure. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. Heart Failure in North America

    OpenAIRE

    Blair, John E. A; Huffman, Mark; Shah, Sanjiv J

    2013-01-01

    Heart failure is a major health problem that affects patients and healthcare systems worldwide. Within the continent of North America, differences in economic development, genetic susceptibility, cultural practices, and trends in risk factors and treatment all contribute to both inter-continental and within-continent differences in heart failure. The United States and Canada represent industrialized countries with similar culture, geography, and advanced economies and infrastructure. During t...

  14. Definition and Classification of Heart Failure

    Directory of Open Access Journals (Sweden)

    Mitja Lainscak

    2017-01-01

    Full Text Available A review of the definition and classification of heart failure, updated since the recent 2016 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure. Heart failure is defined by the European Society of Cardiology (ESC as a clinical syndrome characterised by symptoms such as shortness of breath, persistent coughing or wheezing, ankle swelling and fatigue, that may be accompanied by the following signs: jugular venous pressure, pulmonary crackles, increased heart rate and peripheral oedema. However, these signs may not be present in the early stages and in patients treated with diuretics. When apparent, they are due to a structural and/or functional cardiac abnormality, leading to systolic and/or diastolic ventricular dysfunction, resulting in a reduced cardiac output and/or elevated intra- cardiac pressures at rest or during stress. According to the most recent ESC guidelines the initial evaluation of patients with suspected heart failure should include a clinical history and physical examination, laboratory assessment, chest radiography, and electrocardiography. Echocardiography can confirm the diagnosis. Beyond detecting myocardial abnormality, other impairments such as abnormalities of the valves, pericardium, endocardium, heart rhythm, and conduction may be found. The identification of the underlying aetiology is pivotal for the diagnosis of heart failure and its treatment. The authors review the definitions and classifications of heart failure.

  15. Clipping in Awake Surgery as End-Stage in a Complex Internal Carotid Artery Aneurysm After Failure of Multimodal Endovascular and Extracranial-Intracranial Bypass Treatment.

    Science.gov (United States)

    Cannizzaro, Delia; Peschillo, Simone; Mancarella, Cristina; La Pira, Biagia; Rastelli, Emanuela; Passacantilli, Emiliano; Santoro, Antonio

    2017-06-01

    Intracranial carotid artery aneurysm can be treated via microsurgical or endovascular techniques. The optimal planning is the result of the careful patient selection through clinical, anatomic, and angiographic analysis. We present a case of ruptured internal carotid artery (ICA) aneurysm that became a complex aneurysm after failure of multi-endovascular and surgery treatment. We describe complete trapping in awake craniotomy after failure of coiling, stenting, and bypassing. ICA aneurysms could become complex aneurysms following multi-treatment failure. Endovascular approaches to treat ICA aneurysms include coiling, stenting, flow diverter stenting, and stenting-assisted coiling technique. The role of surgery remains relevant. To avoid severe neurologic deficits, recurrence, and the need of retreatment, a multidisciplinary discussion with experienced endovascular and vascular neurosurgeons is mandatory in such complex cases. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Study of the potential effect of selenium on gamma-radiation induced ovarian failure

    International Nuclear Information System (INIS)

    Said, R.S.M.

    2012-01-01

    Radiotherapy is a major factor contributing to female infertility by inducing premature ovarian failure (POF). Therefore, the need for an effective radioprotective agent is evident. The present study investigated the mechanism of potential radioprotective effect of sodium selenite on radiation-induced ovarian failure and whether sodium selenite can stimulate in vivo follicular development in experimental rats. Immature female Sprague-Dawely rats were either exposed to gamma radiation (3.2 Gy, LD 20 ), once and/or treated with sodium selenite (0.5 mg/kg), once daily for one week before irradiation. Follicular and oocyte development, apoptotic markers, proliferation marker as well as oxidative stress markers were assessed 24-h after irradiation. In addition, fertility assessment was performed after female rats became completely mature at two months of age. Sodium selenite significantly enhanced follicular development as compared to the irradiated group. Sodium selenite significantly reversed the oxidative stress effects of radiation that was evidenced by increasing in lipid peroxide level and decreasing in glutathione level, and glutathione peroxidase (GPx) activity. Assessment of apoptosis and cell proliferation markers revealed that caspase 3 and cytochrome c expressions markedly-increased, whereas, PCNA expression markedly-decreased in the irradiated group; in contrast, sodium selenite treatment prevented these alterations. Histopathological examination further confirmed the radioprotective efficacy of sodium selenite and its in-vivo effect on ovarian follicles’ maturation. In conclusion, sodium selenite showed a radioprotective effect and improved folliculogenesis through increasing ovarian granulosa cells proliferation, estradiol and FSH secretion, and GPx activity, whilst decreasing lipid peroxidation and oxidative stress, leading to inhibition of the apoptosis pathway through decreasing the expressions of caspase 3 and cytochrome c.

  17. Patterns of failure for glioblastoma multiforme following concurrent radiation and temozolomide

    International Nuclear Information System (INIS)

    Dobelbower, Michael C.; Burnett, Omer L. III; Haytt, Mark D.; Fiveash, John B.; Nordal, Robert A.; Nabors, Louis B.; Markert, James M.

    2011-01-01

    To analyse patterns of failure in patients with glioblastoma multiforme treated with concurrent radiation and temozolomide. A retrospective review of patients treated with concurrent radiation and temozolomide was performed. Twenty patients treated at the University of Alabama at Birmingham, with biopsy-proven disease, documented disease progression after treatment, and adequate radiation dosimetry and imaging records were included in the study. Patients generally received 46 Gy to the primary tumour and surrounding oedema plus 1 cm, and 60 Gy to the enhancing tumour plus 1 cm. MRIs documenting failure after therapy were fused to the original treatment plans. Contours of post-treatment tumour volumes were generated from MRIs showing tumour failure and were overlaid onto the original isodose curves. The recurrent tumours were classified as in-field, marginal or regional. Recurrences were also evaluated for distant failure. Of the 20 documented failures, all patients had some component of failure at the primary site. Eighteen patients (90%) failed in-field, 2 patients (10%) had marginal failures, and no regional failures occurred. Four patients (20%) had a component of distant failure in which an independent satellite lesion was located completely outside of the 95% isodose curve. Radiation concurrent with temozolomide appears to be associated with a moderate risk of distant brain failure in addition to the high rate of local failure. The risk of distant failure was consistent with that observed with radiation alone, suggesting that temozolomide does not act to reduce distant brain failure but to improve local control.

  18. Clinical characteristics and causes of heart failure adherence to treatment guidelines and mortality of patients with acute heart failure: Experience at Groote Schuur Hospital Cape Town South Africa

    Directory of Open Access Journals (Sweden)

    P Szymanski

    2018-02-01

    Full Text Available Background. There is limited information on acute heart failure (AHF and its treatment in sub-Saharan Africa.Objective. To describe the clinical characteristics and causes of heart failure (HF, adherence to HF treatment guidelines, and mortality of patients with AHF presenting to Groote Schuur Hospital (GSH, Cape Town, South Africa.Methods. This sub-study of The Sub-Saharan Africa Survey of Heart Failure (THESUS-HF was a prospective and observational survey that focused on the enrolment and follow-up of additional patients with AHF presenting to GSH and entered into the existing registry after publication of the primary THESUS-HF article in 2012. The patients were classified into prevalent (existing or incident (new cases of HF.Results. Of the 119 patients included, 69 (58.0% were female and the mean (standard deviation age was 49.9 (16.3 years. The majority of prevalent cases were patients of mixed ancestry (63.3%, and prevalent cases had more hypertension (70.0%, diabetes mellitus (36.7%, hyperlipidaemia (33.3% and ischaemic heart disease (IHD (36.7% than incident cases. The top five causes of HF were cardiomyopathy (20.2%, IHD (19.3%, rheumatic valvular heart disease (RHD (18.5%, cor pulmonale (11.8% and hypertension (10.1%, with the remaining 20.1% consisting of miscellaneous causes including pericarditis, toxins and congenital heart disease. Most patients received renin-angiotensin system blockers and loop diuretics on discharge. There was a low rate of beta-blocker, aldosterone antagonist and digoxin use. Rehospitalisation within 180 days occurred in 25.2% of cases. In-hospital mortality was 8.4% and the case fatality rate at 6 months was 26.1%.Conclusion. In Cape Town, the main causes of AHF are cardiomyopathy, IHD and RHD. AHF affects a young population and is associated with a high rate of rehospitalisation and mortality. There is serious under-use of beta-blockers, aldosterone antagonists and digoxin. Emphasis on the rigorous

  19. Management of Postoperative Respiratory Failure.

    Science.gov (United States)

    Mulligan, Michael S; Berfield, Kathleen S; Abbaszadeh, Ryan V

    2015-11-01

    Despite best efforts, postoperative complications such as postoperative respiratory failure may occur and prompt recognition of the process and management is required. Postoperative respiratory failure, such as postoperative pneumonia, postpneumonectomy pulmonary edema, acute respiratory distress-like syndromes, and pulmonary embolism, are associated with high morbidity and mortality. The causes of these complications are multifactorial and depend on preoperative, intraoperative, and postoperative factors, some of which are modifiable. The article identifies some of the risk factors, causes, and treatment strategies for successful management of the patient with postoperative respiratory failure. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Pill Properties that Cause Dysphagia and Treatment Failure

    Science.gov (United States)

    Fields, Jeremy; Go, Jorge T.; Schulze, Konrad S.

    2015-01-01

    texture; others cited sharp edges, odd shapes, or bad taste/smell. Extra-large pills were widely loathed, with 4 out of 5 participants preferring to take 3 or more medium-sized pills instead of a single jumbo pill. Conclusions Our survey results suggest that 4 out of 5 adult Americans take several pills daily, and do so without undue effort. It also suggests that half of today’s Americans encounter pills that are hard to swallow. Up to 4% of our participants gave up on treatments because they could not swallow the prescribed pills. Up to 7% categorically rejected taking pills that are hard to swallow. Specific material properties are widely blamed for making pills hard to swallow; extra-large capsules and tablets are universally feared, whereas medium-sized pills with a smooth coating are widely preferred. Our findings suggest that health care providers could minimize treatment failures and complications by prescribing and dispensing pills that are easy to swallow. Industry and regulatory bodies may facilitate this by making swallowability an essential criterion in the design and licensing of oral medications. Such policies could lessen the burden of pill taking for Americans and improve the adherence with prescribed treatments. PMID:26543509

  1. Milrinone for the Treatment of Acute Heart Failure After Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Tang, Xiuying; Liu, Peng; Li, Runjun; Jing, Quanmin; Lv, Junhao; Liu, Li; Liu, Yingfeng

    2015-09-01

    Despite advancements in modern medicine, the treatment of acute heart failure (AHF) after acute myocardial infarction (AMI) remains challenging. Milrinone is effective in the treatment of chronic congestive heart failure, but its safety and efficacy in patients with AHF after AMI have not been systematically evaluated. This meta-analysis was performed to assess the safety and efficacy of milrinone in patients with AHF after AMI. We used a pre-designed protocol to search electronic databases for randomized trials assessing milrinone for the treatment of AHF after AMI. Data were abstracted from relevant studies. Heterogeneity was assessed qualitatively using a Q test and quantified using the I(2) statistic. Pooled risk estimates with 95% confidence intervals (CIs) were obtained using fixed-effects models unless substantial heterogeneity was observed (I(2) ≥ 50% and heterogeneity p ≤ 0.1). Four randomized trials met the inclusion criteria. However, there were no significant differences in deaths, blood pressure, premature ventricular contractions, gastrointestinal reactions, or ventricular tachycardia or fibrillation (all p > 0.05) between control group and milrinone treatment group. Pooled estimates showed that milrinone significantly increased the left ventricular ejection fraction (MD 5.69; 95% CI 4.27 to 7.10; p milrinone may be safe and effective for patients with AHF after AMI. However, this meta-analysis did not show that milrinone could improve prognosis or the survival rate. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  2. FDG PET/CT patterns of treatment failure of malignant pleural mesothelioma: relationship to histologic type, treatment algorithm, and survival

    Energy Technology Data Exchange (ETDEWEB)

    Gerbaudo, Victor H.; Mamede, Marcelo [Brigham and Women' s Hospital, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Boston, MA (United States); Trotman-Dickenson, Beatrice; Hatabu, Hiroto [Brigham and Women' s Hospital, Harvard Medical School, Division of Thoracic Radiology, Boston, MA (United States); Sugarbaker, David J. [Brigham and Women' s Hospital, Harvard Medical School, Division of Thoracic Surgery, Boston, MA (United States)

    2011-05-15

    This study investigated the diagnostic performance and prognostic value of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in suspected malignant pleural mesothelioma (MPM) recurrence, in the context of patterns and intensity of FDG uptake, histologic type, and treatment algorithm. Fifty patients with MPM underwent FDG PET/CT for restaging 11 {+-} 6 months after therapy. Tumor relapse was confirmed by histopathology, and by clinical evolution and subsequent imaging. Progression-free survival was defined as the time between treatment and the earliest clinical evidence of recurrence. Survival after FDG PET/CT was defined as the time between the scan and death or last follow-up. Overall survival was defined as the time between initial treatment and death or last follow-up date. Treatment failure was confirmed in 42 patients (30 epithelial and 12 non-epithelial MPM). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for FDG PET/CT were 97.6, 75, 94, 86, and 95.3%, respectively. FDG PET/CT evidence of single site of recurrence was observed in the ipsilateral hemithorax in 18 patients (44%), contralaterally in 2 (5%), and in the abdomen in 1 patient (2%). Bilateral thoracic relapse was detected in three patients (7%). Simultaneous recurrence in the ipsilateral hemithorax and abdomen was observed in ten (24%) patients and in seven (17%) in all three cavities. Unsuspected distant metastases were detected in 11 patients (26%). Four patterns of uptake were observed in recurrent disease: focal, linear, mixed (focal/linear), and encasing, with a significant difference between the intensity of uptake in malignant lesions compared to benign post-therapeutic changes. Lesion uptake was lower in patients previously treated with more aggressive therapy and higher in intrathoracic lesions of patients with distant metastases. FDG PET/CT helped in the selection of 12 patients (29%) who benefited from additional previously

  3. FDG PET/CT patterns of treatment failure of malignant pleural mesothelioma: relationship to histologic type, treatment algorithm, and survival

    International Nuclear Information System (INIS)

    Gerbaudo, Victor H.; Mamede, Marcelo; Trotman-Dickenson, Beatrice; Hatabu, Hiroto; Sugarbaker, David J.

    2011-01-01

    This study investigated the diagnostic performance and prognostic value of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in suspected malignant pleural mesothelioma (MPM) recurrence, in the context of patterns and intensity of FDG uptake, histologic type, and treatment algorithm. Fifty patients with MPM underwent FDG PET/CT for restaging 11 ± 6 months after therapy. Tumor relapse was confirmed by histopathology, and by clinical evolution and subsequent imaging. Progression-free survival was defined as the time between treatment and the earliest clinical evidence of recurrence. Survival after FDG PET/CT was defined as the time between the scan and death or last follow-up. Overall survival was defined as the time between initial treatment and death or last follow-up date. Treatment failure was confirmed in 42 patients (30 epithelial and 12 non-epithelial MPM). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for FDG PET/CT were 97.6, 75, 94, 86, and 95.3%, respectively. FDG PET/CT evidence of single site of recurrence was observed in the ipsilateral hemithorax in 18 patients (44%), contralaterally in 2 (5%), and in the abdomen in 1 patient (2%). Bilateral thoracic relapse was detected in three patients (7%). Simultaneous recurrence in the ipsilateral hemithorax and abdomen was observed in ten (24%) patients and in seven (17%) in all three cavities. Unsuspected distant metastases were detected in 11 patients (26%). Four patterns of uptake were observed in recurrent disease: focal, linear, mixed (focal/linear), and encasing, with a significant difference between the intensity of uptake in malignant lesions compared to benign post-therapeutic changes. Lesion uptake was lower in patients previously treated with more aggressive therapy and higher in intrathoracic lesions of patients with distant metastases. FDG PET/CT helped in the selection of 12 patients (29%) who benefited from additional previously

  4. The internalization of Helicobacter pylori plays a role in the failure of H. pylori eradication.

    Science.gov (United States)

    Wang, You-Hua; Lv, Zhi-Fa; Zhong, Yao; Liu, Dong-Sheng; Chen, Shu-Ping; Xie, Yong

    2017-02-01

    Helicobacter pylori (H. pylori) internalization involves invasion of cells by the bacterium. Several studies have shown that H. pylori can invade human gastric epithelial cells, immune cells, and Candida yeast in vivo and in vitro. Whether bacterial invasion plays a role in eradication failure is unclear. To investigate the relationship between H. pylori invasion of GES-1 cells and H. pylori eradication failure. Forty-two clinical strains isolated from H. pylori-positive patients with different outcomes after treatment with furazolidone-based therapy were examined (17 failures and 25 successes). The H. pylori strains were shown to be susceptible to amoxicillin and furazolidone, and the patients also exhibited good compliance. Genotyping was performed for cagA and vacA (s and m). The antibiotic susceptibility of the strains to amoxicillin, furazolidone, clarithromycin, metronidazole, and levofloxacin was determined by E-tests. The levels of H. pylori invasion of GES-1 cells were detected by gentamicin colony-forming unit assays. The internalization level in the eradication success group was 5.40±5.78 × 10 -3  cfu/cell, and the median was 6.194 × 10 -3  cfu/cell; the internalization level in the eradication failure group was 8.98±5.40 × 10 -3  cfu/cell, and the median was 10.28 × 10 -3  cfu/cell. The eradication failure group showed a greater invasion level than the eradication success group (Pinternalization levels were compared (P>.05). The results showed that H. pylori invasion of the gastric epithelia might play a role in eradication failure. © 2016 John Wiley & Sons Ltd.

  5. Diabetes Mellitus and Heart Failure.

    Science.gov (United States)

    Lehrke, Michael; Marx, Nikolaus

    2017-06-01

    Epidemiologic and clinical data from the last 2 decades have shown that the prevalence of heart failure in diabetes is very high, and the prognosis for patients with heart failure is worse in those with diabetes than in those without diabetes. Experimental data suggest that various mechanisms contribute to the impairment in systolic and diastolic function in patients with diabetes, and there is an increased recognition that these patients develop heart failure independent of the presence of coronary artery disease or its associated risk factors. In addition, current clinical data demonstrated that treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin reduced hospitalization for heart failure in patients with type 2 diabetes mellitus and high cardiovascular risk. This review article summarizes recent data on the prevalence, prognosis, pathophysiology, and therapeutic strategies to treat patients with diabetes and heart failure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Pediatric Hydrocephalus in Ethiopia: Treatment Failures and Infections: A Hospital-Based, Retrospective Study.

    Science.gov (United States)

    Laeke, Tsegazeab; Tirsit, Abenezer; Biluts, Hagos; Murali, Deeptha; Wester, Knut

    2017-04-01

    Treatment of pediatric hydrocephalus in sub-Saharan countries is associated with significant complication rates. The objective of this study is to analyze the management of hydrocephalus and complication rates of surgical intervention in the Ethiopian setting to improve future quality. A retrospective cohort study was conducted in a neurosurgical teaching hospital. Two cohorts separated by 2.5 years were analyzed. A total of 128 (58.6% male and 41.4% female) children with isolated hydrocephalus, meningomyelocele (MMC)-related hydrocephalus, or MMC without hydrocephalus were included. Their age ranged from 1 day to 5 years, for a mean age of 7.2 months (median age 2 months). One hundred thirteen patients had hydrocephalus, of whom 57 (44.5.3%) had isolated hydrocephalus and 56 (43.8%) had hydrocephalus associated with MMC. Seventy-seven (74.7%) patients underwent ventriculoperitoneal (VP) shunting, whereas 24 (23.3%) underwent endoscopic third ventriculostomy (ETV). The incidence of shunt infection was 23.4%. Reoperation was needed in 54 (52.4%) patients, with the most common indication being shunt failure. ETV failed in 14 (58.3%) of the 24 patients undergoing ETV. VP shunt insertions had unacceptably high infection rate despite the presence of a protocol for the procedure. Intraoperative guidelines should be developed further and followed strictly to reduce infections. Such measures should include restricting the number of surgeons performing the procedure. In our opinion, one should avoid insertion of a VP shunt as the primary treatment. ETV has proved to be a good alternative in other studies and the decreasing pattern of ETV failure in our study also suggest ETV as a better alternative to VP shunt. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Influence of diabetes mellitus on heart failure risk and outcome

    Directory of Open Access Journals (Sweden)

    Van Belle Eric

    2003-01-01

    Full Text Available Abstract Our aim is to summarize and discuss the recent literature linking diabetes mellitus with heart failure, and to address the issue of the optimal treatment for diabetic patients with heart failure. The studies linking diabetes mellitus (DM with heart failure (HF The prevalence of diabetes mellitus in heart failure populations is close to 20% compared with 4 to 6% in control populations. Epidemiological studies have demonstrated an increased risk of heart failure in diabetics; moreover, in diabetic populations, poor glycemic control has been associated with an increased risk of heart failure. Various mechanisms may link diabetes mellitus to heart failure: firstly, associated comorbidities such as hypertension may play a role; secondly, diabetes accelerates the development of coronary atherosclerosis; thirdly, experimental and clinical studies support the existence of a specific diabetic cardiomyopathy related to microangiopathy, metabolic factors or myocardial fibrosis. Subgroup analyses of randomized trials demonstrate that diabetes is also an important prognostic factor in heart failure. In addition, it has been suggested that the deleterious impact of diabetes may be especially marked in patients with ischemic cardiomyopathy. Treatment of heart failure in diabetic patients The knowledge of the diabetic status may help to define the optimal therapeutic strategy for heart failure patients. Cornerstone treatments such as ACE inhibitors or beta-blockers appear to be uniformly beneficial in diabetic and non diabetic populations. However, in ischemic cardiomyopathy, the choice of the revascularization technique may differ according to diabetic status. Finally, clinical studies are needed to determine whether improved metabolic control might favorably influence the outcome of diabetic heart failure patients.

  8. Family Partner Intervention Influences Self-Care Confidence and Treatment Self-Regulation in Patients with Heart Failure

    Science.gov (United States)

    Stamp, Kelly D.; Dunbar, Sandra B.; Clark, Patricia C.; Reilly, Carolyn M.; Gary, Rebecca A.; Higgins, Melinda; Ryan, Richard M

    2015-01-01

    Background Heart failure self-care requires confidence in one’s ability and motivation to perform a recommended behavior. Most self-care occurs within a family context, yet little is known about the influence of family on heart failure self-care or motivating factors. Aims To examine the association of family functioning and the self-care antecedents of confidence and motivation among heart failure participants and determine if a family partnership intervention would promote higher levels of perceived confidence and treatment self-regulation (motivation) at four and eight months compared to patient-family education or usual care groups. Methods Heart failure patients (N = 117) and a family member were randomized to a family partnership intervention, patient-family education or usual care groups. Measures of patient’s perceived family functioning, confidence, motivation for medications and following a low-sodium diet were analyzed. Data were collected at baseline, four and eight months. Results Family functioning was related to self-care confidence for diet (p=.02) and autonomous motivation for adhering to their medications (p=.05 and diet p=0.2). The family partnership intervention group significantly improved confidence (p=.05) and motivation (medications (p=.004; diet p=.012) at four months whereas patient-family education group and usual care did not change. Conclusion Perceived confidence and motivation for self-care was enhanced by family partnership intervention, regardless of family functioning. Poor family functioning at baseline contributed to lower confidence. Family functioning should be assessed to guide tailored family-patient interventions for better outcomes. PMID:25673525

  9. Fatal Acute Liver Failure as a Consequence of Regorafenib Treatment in a Metastatic Colon Cancer

    Directory of Open Access Journals (Sweden)

    Dominique Béchade

    2017-08-01

    Full Text Available Regorafenib is a multikinase inhibitor which showed benefits in pretreated metastatic colorectal cancer patients. Hepatotoxicity has been described as a frequent side effect. We report the case of a 65-year-old patient presenting with jaundice, fever, and hepatocellular insufficiency which led to death of the patient. She had previously been treated with several lines of chemotherapy for sub- and diaphragmatic ganglionic metastases of a colon adenocarcinoma. There were no liver metastases. The fatal liver failure occurred at the beginning of treatment with regorafenib at a dosage of 3 tablets per day. No concomitant treatment was given, and other causes of liver damage were eliminated. The liver biopsy showed hepatocyte necrosis with lymphocyte infiltration. This observation illustrates the risk of severe hepatic involvement typically occurring within the first 2 months of treatment. Monitoring liver biology every 2 weeks is essential during the first 2 months to detect any hepatotoxicity.

  10. Solid Lipid Nanoparticles Carrying Temozolomide for Melanoma Treatment. Preliminary In Vitro and In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Nausicaa Clemente

    2018-01-01

    Full Text Available Aim: To develop an innovative delivery system for temozolomide (TMZ in solid lipid nanoparticles (SLN, which has been preliminarily investigated for the treatment of melanoma. Materials and Methods: SLN-TMZ was obtained through fatty acid coacervation. Its pharmacological effects were assessed and compared with free TMZ in in vitro and in vivo models of melanoma and glioblastoma. Results: Compared to the standard free TMZ, SLN-TMZ exerted larger effects, when cell proliferation of melanoma cells, and neoangiogeneis were evaluated. SLN-TMZ also inhibited growth and vascularization of B16-F10 melanoma in C57/BL6 mice, without apparent toxic effects. Conclusion: SLN could be a promising strategy for the delivery of TMZ, allowing an increased stability of the drug and thereby its employment in the treatment of aggressive malignacies.

  11. Solid Lipid Nanoparticles Carrying Temozolomide for Melanoma Treatment. Preliminary In Vitro and In Vivo Studies

    Science.gov (United States)

    Ferrara, Benedetta; Biasibetti, Elena; Schiffer, Davide; Mellai, Marta; Annovazzi, Laura; Cangemi, Luigi; Muntoni, Elisabetta; Dianzani, Umberto

    2018-01-01

    Aim: To develop an innovative delivery system for temozolomide (TMZ) in solid lipid nanoparticles (SLN), which has been preliminarily investigated for the treatment of melanoma. Materials and Methods: SLN-TMZ was obtained through fatty acid coacervation. Its pharmacological effects were assessed and compared with free TMZ in in vitro and in vivo models of melanoma and glioblastoma. Results: Compared to the standard free TMZ, SLN-TMZ exerted larger effects, when cell proliferation of melanoma cells, and neoangiogeneis were evaluated. SLN-TMZ also inhibited growth and vascularization of B16-F10 melanoma in C57/BL6 mice, without apparent toxic effects. Conclusion: SLN could be a promising strategy for the delivery of TMZ, allowing an increased stability of the drug and thereby its employment in the treatment of aggressive malignacies. PMID:29364157

  12. New approaches to the treatments of short bowel syndrome-associated intestinal failure

    DEFF Research Database (Denmark)

    Jeppesen, Palle B

    2014-01-01

    PURPOSE OF REVIEW: Teduglutide, a recombinant analog of human glucagon-like peptide 2, has recently been approved in the US and Europe (Gattex and Revestive, respectively) as the first targeted treatment of short bowel syndrome-associated intestinal failure (SBS-IF). Glucagon-like peptide 2...... improves structural and functional intestinal adaptation following intestinal resection by decelerating a rapid gastric emptying, by decreasing gastric hypersecretion, by increasing intestinal blood flow and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 studies...... energy losses by approximately 0.8 MJ/day (∼200 kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Teduglutide had an acceptable tolerability profile, where adverse events generally were of gastrointestinal origin consistent...

  13. Rational use of inotropic therapy in heart failure.

    Science.gov (United States)

    Felker, G M; O'Connor, C M

    2001-03-01

    Despite their theoretic appeal, agents that increase cardiac contractility (positive inotropes) have consistently been shown to increase mortality when given chronically to patients with heart failure. The routine use of inotropes as heart failure therapy in either the acute or the chronic setting is not supported by the available data. Some appropriate uses of inotropes are as temporary treatment of diuretic-refractory acute heart failure decompensations, or as a bridge to definitive treatment such as revascularization or cardiac transplantation. Although controversial, the use of inotropes as a palliative measure in the small subset of patients with truly end-stage heart failure may be appropriate. An understanding of the appropriate goals of therapy is important for both patients and physicians if rational decisions about the use of inotropes are to be made.

  14. Ex vivo piperaquine resistance developed rapidly in Plasmodium falciparum isolates in northern Cambodia compared to Thailand

    Directory of Open Access Journals (Sweden)

    Suwanna Chaorattanakawee

    2016-10-01

    Full Text Available Abstract Background The recent dramatic decline in dihydroartemisinin-piperaquine (DHA-PPQ efficacy in northwestern Cambodia has raised concerns about the rapid spread of piperaquine resistance just as DHA-PPQ is being introduced as first-line therapy in neighbouring countries. Methods Ex vivo parasite susceptibilities were tracked to determine the rate of progression of DHA, PPQ and mefloquine (MQ resistance from sentinel sites on the Thai–Cambodian and Thai–Myanmar borders from 2010 to 2015. Immediate ex vivo (IEV histidine-rich protein 2 (HRP-2 assays were used on fresh patient Plasmodium falciparum isolates to determine drug susceptibility profiles. Results IEV HRP-2 assays detected the precipitous emergence of PPQ resistance in Cambodia beginning in 2013 when 40 % of isolates had an IC90 greater than the upper limit of prior years, and this rate doubled to 80 % by 2015. In contrast, Thai–Myanmar isolates from 2013 to 14 remained PPQ-sensitive, while northeastern Thai isolates appeared to have an intermediate resistance profile. The opposite trend was observed for MQ where Cambodian isolates appeared to have a modest increase in overall sensitivity during the same period, with IC50 declining to median levels comparable to those found in Thailand. A significant association between increased PPQ IC50 and IC90 among Cambodian isolates with DHA-PPQ treatment failure was observed. Nearly all Cambodian and Thai isolates were deemed artemisinin resistant with a >1 % survival rate for DHA in the ring-stage assay (RSA, though there was no correlation among isolates to indicate cross-resistance between PPQ and artemisinins. Conclusions Clinical DHA-PPQ failures appear to be associated with declines in the long-acting partner drug PPQ, though sensitivity appears to remain largely intact for now in western Thailand. Rapid progression of PPQ resistance associated with DHA-PPQ treatment failures in northern Cambodia limits drugs of choice in

  15. Effects of unplanned treatment interruptions on HIV treatment failure– results from TAHOD

    Science.gov (United States)

    Jiamsakul, Awachana; Kerr, Stephen J.; Ng, Oon Tek; Lee, Man Po; Chaiwarith, Romanee; Yunihastuti, Evy; Van Nguyen, Kinh; Pham, Thuy Thanh; Kiertiburanakul, Sasisopin; Ditangco, Rossana; Saphonn, Vonthanak; Sim, Benedict L. H.; Merati, Tuti Parwati; Wong, Wingwai; Kantipong, Pacharee; Zhang, Fujie; Choi, Jun Yong; Pujari, Sanjay; Kamarulzaman, Adeeba; Oka, Shinichi; Mustafa, Mahiran; Ratanasuwan, Winai; Petersen, Boondarika; Law, Matthew; Kumarasamy, Nagalingeswaran

    2016-01-01

    Objectives Treatment interruptions (TI) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia. Methods Patients initiating cART between 2006-2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Co-variables with p30 days were associated with failure (31-180 days HR=2.66, 95%CI (1.70-4.16); 181-365 days HR=6.22, 95%CI (3.26-11.86); and >365 days HR=9.10, 95% CI (4.27-19.38), all pfailure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption. PMID:26950901

  16. Radiotherapy in desmoid tumors. Treatment response, local control, and analysis of local failures

    Energy Technology Data Exchange (ETDEWEB)

    Santti, Kirsi; Beule, Annette; Tuomikoski, Laura; Jaeaeskelaeinen, Anna-Stina; Saarilahti, Kauko; Tarkkanen, Maija; Blomqvist, Carl [Helsinki University Hospital and University of Helsinki, Comprehensive Cancer Center, Helsinki (Finland); Roenty, Mikko [HUSLAB and University of Helsinki, Department of Pathology, Helsinki (Finland); Ihalainen, Hanna [Helsinki University Hospital and University of Helsinki, Department of Plastic Surgery, Helsinki (Finland)

    2017-04-15

    Desmoid tumors (aggressive fibromatosis) are rare soft tissue tumors which frequently recur after surgery. Desmoid tumors arise from musculoaponeurotic tissue in the extremities, head and neck, abdominal wall, or intra-abdominally. Our aim was to examine the outcome of radiotherapy of desmoid tumors in a single institution series. We evaluated 41 patients with desmoid tumors treated with 49 radiotherapies between 1987 and 2012. Radiologic images for response evaluation were reassessed and responses to treatment registered according to RECIST criteria 1.1. For patients with local failures radiation dose distribution was determined in each local failure volume using image co-registration. Recurrences were classified as in-target, marginal, or out-of-target. Prognostic factors for radiotherapy treatment failure were evaluated. Radiotherapy doses varied from 20-63 Gy (median 50 Gy) with a median fraction size of 2 Gy. The objective response rate to definitive radiotherapy was 55% (12/22 patients). Median time to response was 14 months. A statistically significant dose-response relation for definitive and postoperative radiotherapy was observed both in univariate (p-value 0.002) and in multivariate analysis (p-value 0.02) adjusted for potential confounding factors. Surgery before radiotherapy or surgical margin had no significant effect on time to progression. Nine of 11 (82%) local failures were classified as marginal and two of 11 (18%) in-target. None of the recurrences occurred totally out-of-target. Radiotherapy is a valuable option for treating desmoid tumors. Radiotherapy dose appears to be significantly associated to local control. (orig.) [German] Desmoide (aggressive Fibromatosen) sind seltene Weichteiltumore der muskulaeren Membranen von Kopf, Hals, Extremitaeten und Bauchwand. Ziel war es, die Wirksamkeit der Strahlentherapie bei aggressiver Fibromatose an einer einzelnen Klinik zu untersuchen. Ausgewertet wurden 41 Patienten mit aggressiver Fibromatose, die

  17. Efficacy of carvedilol in pediatric heart failure

    DEFF Research Database (Denmark)

    Christensen, Alex Hørby; Fatkin, Diane

    2013-01-01

    Evaluation of: Huang M, Zhang X, Chen S et al. The effect of carvedilol treatment on chronic heart failure in pediatric patients with dilated cardiomyopathy: a prospective, randomized-controlled study. Pediatr. Cardiol. 34, 680-685 (2013). A role for β-blockers in children with heart failure has...

  18. Rationale, design and baseline results of the Treatment Optimisation in Primary care of Heart failure in the Utrecht region (TOPHU) study : a cluster randomised controlled trial

    NARCIS (Netherlands)

    Valk, Mark J.; Hoes, Arno W.; Mosterd, Arend; Landman, Marcel A.; Broekhuizen, Berna D L; Rutten, Frans H.

    2015-01-01

    BACKGROUND: Heart failure (HF) is mainly detected and managed in primary care, but the care is considered suboptimal. We present the rationale, design and baseline results of the Treatment Optimisation in Primary care of Heart failure in the Utrecht region (TOPHU) study. In this study we assess the

  19. German disease management guidelines: surgical therapies for chronic heart failure.

    Science.gov (United States)

    Sindermann, J R; Klotz, S; Rahbar, K; Hoffmeier, A; Drees, G

    2010-02-01

    The German Disease Management Guideline "Chronic Heart Failure" intends to guide physicians working in the field of diagnosis and treatment of heart failure. The guideline provides a tool on the background of evidence based medicine. The following short review wants to give insights into the role of some surgical treatment options to improve heart failure, such as revascularization, ventricular reconstruction and aneurysmectomy, mitral valve reconstruction, ventricular assist devices and heart transplantation. (c) Georg Thieme Verlag KG Stuttgart-New York.

  20. Nelfinavir is effective against human cervical cancer cells in vivo: a potential treatment modality in resource-limited settings

    Directory of Open Access Journals (Sweden)

    Davis MA

    2016-06-01

    Full Text Available Mitzie-Ann Davis,* Joe R Delaney,* Chandni B Patel, Ryan Storgard, Dwayne G Stupack Division of Gynecologic Oncology, Department of Reproductive Medicine, Rebecca and John UCSD Moores Cancer Center, La Jolla, CA, USA *These authors contributed equally to this work Objective: The standard treatment for cervical cancer in developed countries includes surgery and chemoradiation, with standard of care lagging in developing countries. Even in the former case, treatment frequently yields recalcitrant tumors and women succumb to disease. Here we examine the impact of nelfinavir, an off-patent viral protease inhibitor, which has shown promise as an antineoplastic agent. Methods: We evaluated the morphological and proliferative effects of the autophagy-stressing drug nelfinavir in normal and cisplatin-resistant cervical cancer cells. Immunofluorescent validation of autophagy markers was performed and the impact of nelfinavir in an in vivo model of tumor growth was determined. Results: Nelfinavir exhibits cytotoxicity against both cisplatin-sensitive and -resistant ME-180 human cervical cancer cells in vitro and in vivo. Immunoblotting and immunofluorescence showed an expression of the autophagy marker LC3-II in response to nelfinavir treatment. Conclusion: Nelfinavir, now available as an inexpensive generic orally dosed agent (Nelvir, is cytotoxic against cervical cancer cells. It acts by burdening the autophagy pathway to impair tumor cell survival and a modest induction of apoptosis. While further studies are needed to elucidate the optimal method of application of nelfinavir, it may represent an appealing global option for the treatment of cervical cancer. Keywords: cervical cancer, nelfinavir, cisplatin resistance, autophagy, responsible medicine

  1. rpsftm: An R package for rank preserving structural failure time models

    OpenAIRE

    Allison, A.; White, I. R.; Bond, S.

    2017-01-01

    Treatment switching in a randomised controlled trial occurs when participants change from their randomised treatment to the other trial treatment during the study. Failure to account for treatment switching in the analysis (i.e. by performing a standard intention-to-treat analysis) can lead to biased estimates of treatment efficacy. The rank preserving structural failure time model (RPSFTM) is a method used to adjust for treatment switching in trials with survival outcomes. The RPSFTM is due ...

  2. Effect of Bacterial Endotoxins on Superovulated Mouse Embryos In Vivo: Is CSF-1 Involved in Endotoxin-Induced Pregnancy Loss?

    Directory of Open Access Journals (Sweden)

    Yogesh Kumar Jaiswal

    2006-01-01

    Full Text Available Mammalian embryonic development is regulated by several cytokines and growth factors from embryonic or maternal origins. Since CSF-1 plays important role in embryonic development and implantation, we investigated its role in gram-negative bacterial LPS-induced implantation failure. The effect of LPS on normal (nonsuperovulated and superovulated in vivo-produced embryos was assessed by signs of morphological degeneration. A significantly similar number of morphologically degenerated embryos recovered from both nonsuperovulated and superovulated LPS treated animals on day 2.5 of pregnancy onwards were morphologically and developmentally abnormal as compared to their respective controls (P < .001. Normal CSF-1 expression level and pattern were also altered through the preimplantation period in the mouse embryos and uterine horns after LPS treatment. This deviation from the normal pattern and level of CSF-1 expression in the preimplantation embryos and uterine tissues suggest a role for CSF-1 in LPS-induced implantation failure.

  3. 20 CFR 416.1725 - Effect of your failure to comply with treatment requirements for your drug addiction or alcoholism.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Effect of your failure to comply with treatment requirements for your drug addiction or alcoholism. 416.1725 Section 416.1725 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Referral of Persons Eligible for Supplemental Security...

  4. Comparative study of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma indicate macrophage infiltration contribute to tumor ablation in vivo.

    Directory of Open Access Journals (Sweden)

    Xinhua Chen

    Full Text Available BACKGROUND AND AIM: Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. MATERIALS AND METHODS: Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. RESULTS: In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. CONCLUSION: The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo.

  5. Albuminuria in heart failure : what do we really know?

    NARCIS (Netherlands)

    Dobre, Daniela; Nimade, Sandeep; de Zeeuw, Dick

    Purpose of the review To describe the role of albuminuria as a risk marker for heart failure and a predictor for treatment effect on heart failure prognosis. Recent findings The level of albumin in the urine is a predictor of heart failure in the general population and in patients with

  6. Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment: in vitro and in vivo studies.

    Science.gov (United States)

    Gunetti, Monica; Noghero, Alessio; Molla, Fabiola; Staszewsky, Lidia Irene; de Angelis, Noeleen; Soldo, Annarita; Russo, Ilaria; Errichiello, Edoardo; Frasson, Chiara; Rustichelli, Deborah; Ferrero, Ivana; Gualandris, Anna; Berger, Massimo; Geuna, Massimo; Scacciatella, Paolo; Basso, Giuseppe; Marra, Sebastiano; Bussolino, Federico; Latini, Roberto; Fagioli, Franca

    2011-10-01

    Bone marrow (BM)-derived cells appear to be a promising therapeutic source for the treatment of acute myocardial infarction (AMI). However, the quantity and quality of the cells to be used, along with the appropriate time of administration, still need to be defined. We thus investigated the use of BM CD34(+)-derived cells as cells suitable for a cell therapy protocol (CTP) in the treatment of experimental AMI. The need for a large number of cells was satisfied by the use of a previously established protocol allowing the expansion of human CD34(+) cells isolated from neonatal and adult hematopoietic tissues. We evaluated gene expression, endothelial differentiation potential and cytokine release by BM-derived cells during in vitro culture. Basal and expanded CD34(+) cells were used as a delivery product in a murine AMI model consisting of a coronary artery ligation (CAL). Cardiac function recovery was evaluated after injecting basal or expanded cells. Gene expression analysis of in vitro-expanded cells revealed that endothelial markers were up-regulated during culture. Moreover, expanded cells generated a CD14(+) subpopulation able to differentiate efficiently into VE-cadherin-expressing cells. In vivo, we observed a cardiac function recovery in mice sequentially treated with basal and expanded cells injected 4 h and 7 days after CAL, respectively. Our data suggest that combining basal and expanded BM-derived CD34(+) cells in a specific temporal pattern of administration might represent a promising strategy for a successful cell-based therapy.

  7. Cost-Effectiveness of Sacubitril-Valsartan Combination Therapy Compared With Enalapril for the Treatment of Heart Failure With Reduced Ejection Fraction.

    Science.gov (United States)

    King, Jordan B; Shah, Rashmee U; Bress, Adam P; Nelson, Richard E; Bellows, Brandon K

    2016-05-01

    The objective of this study was to determine the cost-effectiveness and cost per quality-adjusted life year (QALY) gained of sacubitril-valsartan relative to enalapril for treatment of heart failure with reduced ejection fraction (HFrEF). Compared with enalapril, combination angiotensin receptor-neprilysin inhibition (ARNI), as is found in sacubitril-valsartan, reduces cardiovascular death and heart failure hospitalization rates in patients with HFrEF. Using a Markov model, costs, effects, and cost-effectiveness were estimated for sacubitril-valsartan and enalapril therapies for the treatment of HFrEF. Patients were 60 years of age at model entry and were modeled over a lifetime (40 years) from a third-party payer perspective. Clinical probabilities were derived predominantly from PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). All costs and effects were discounted at a 3% rate annually and are presented in 2015 U.S. dollars. In the base case, sacubitril-valsartan, compared with enalapril, was more costly ($60,391 vs. $21,758) and more effective (6.49 vs. 5.74 QALYs) over a lifetime. The cost-effectiveness of sacubitril-valsartan was highly dependent on duration of treatment, ranging from $249,411 per QALY at 3 years to $50,959 per QALY gained over a lifetime. Sacubitril-valsartan may be a cost-effective treatment option depending on the willingness-to-pay threshold. Future investigations should incorporate real-world evidence with sacubitril-valsartan to further inform decision making. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder.

    Science.gov (United States)

    Bispo, Miguel; Valente, Ana; Maldonado, Rosário; Palma, Rui; Glória, Helena; Nóbrega, João; Alexandrino, Paula

    2009-06-21

    Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.

  9. The usefulness of twenty-four molecular markers in predicting treatment outcome with combination therapy of amodiaquine plus sulphadoxine-pyrimethamine against falciparum malaria in Papua New Guinea

    Directory of Open Access Journals (Sweden)

    Reeder John C

    2008-04-01

    Full Text Available Abstract Background In Papua New Guinea (PNG, combination therapy with amodiaquine (AQ or chloroquine (CQ plus sulphadoxine-pyrimethamine (SP was introduced as first-line treatment against uncomplicated malaria in 2000. Methods We assessed in vivo treatment failure rates with AQ+SP in two different areas in PNG and twenty-four molecular drug resistance markers of Plasmodium falciparum were characterized in pre-treatment samples. The aim of the study was to investigate the association between infecting genotype and treatment response in order to identify useful predictors of treatment failure with AQ+SP. Results In 2004, Day-28 treatment failure rates for AQ+SP were 29% in the Karimui and 19% in the South Wosera area, respectively. The strongest independent predictors for treatment failure with AQ+SP were pfmdr1 N86Y (OR = 7.87, p pfdhps A437G (OR = 3.44, p pfcrt K76T, A220S, N326D, and I356L did not help to increase the predictive value, the most likely reason being that these mutations reached almost fixed levels. Though mutations in SP related markers pfdhfr S108N and C59R were not associated with treatment failure, they increased the predictive value of pfdhps A437G. The difference in treatment failure rate in the two sites was reflected in the corresponding genetic profile of the parasite populations, with significant differences seen in the allele frequencies of mutant pfmdr1 N86Y, pfmdr1 Y184F, pfcrt A220S, and pfdhps A437G. Conclusion The study provides evidence for high levels of resistance to the combination regimen of AQ+SP in PNG and indicates which of the many molecular markers analysed are useful for the monitoring of parasite resistance to combinations with AQ+SP.

  10. Histological study of subcutaneous fat at NIR laser treatment of the rat skin in vivo

    Science.gov (United States)

    Yanina, I. Y.; Svenskaya, Yu. I.; Navolokin, N. A.; Matveeva, O. V.; Bucharskaya, A. B.; Maslyakova, G. N.; Gorin, D. A.; Sukhorukov, G. B.; Tuchin, V. V.

    2015-07-01

    The goal of this work is to quantify impact of in vivo photochemical treatment using indocyanine green (ICG) or encapsulated ICG and NIR laser irradiation through skin of rat with obesity by the follow up tissue sampling and histochemistry. After 1 hour elapsed since 1-min light exposure samples of rat skin with subcutaneous tissue of thickness of 1.5-2.5 mm were taken by surgery from rats within marked 4-zones of the skin site. For hematoxylin-eosin histological examination of excised tissue samples, fixation was carried out by 10%-formaldehyde solution. For ICG and encapsulated ICG subcutaneous injection and subsequent 1-min diode laser irradiation with power density of 8 W/cm2, different necrotic regions with lipolysis of subcutaneous fat were observed. The obtained data can be used for safe layer-by-layer laser treatment of obesity and cellulite.

  11. PATIENT WITH CHRONIC HEART FAILURE. RATIONAL CHOICE OF THERAPY

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2017-01-01

    Full Text Available The theory of chronic hyperactivation of neurohormonal systems, in particular, sympathoadrenal and renin-angiotensin-aldosterone, is the basis of modern concepts of the pathogenesis of heart failure. The medicinal blocking of these two systems has proved to be effective in the treatment of heart failure with reduced ejection fraction (<40%. Antagonists of mineralocorticoid receptors, along with angiotensin-converting enzyme inhibitors and beta-blockers, are neurohumoral modulators. They are used to treat patients with heart failure with reduced ejection fraction. The prescription of mineralocorticoid receptor antagonists in clinical practice remains insufficient despite their high efficacy. Demonstration of the site of mineralocorticoid receptor antagonists in the complex treatment of a patient with chronic heart failure and diabetes type 2 is the goal of this article.

  12. Metronomic capecitabine as second-line treatment in hepatocellular carcinoma after sorafenib failure.

    Science.gov (United States)

    Granito, Alessandro; Marinelli, Sara; Terzi, Eleonora; Piscaglia, Fabio; Renzulli, Matteo; Venerandi, Laura; Benevento, Francesca; Bolondi, Luigi

    2015-06-01

    No standard second-line treatments are available for hepatocellular carcinoma patients who fail sorafenib therapy. We assessed the safety and efficacy of metronomic capecitabine after first-line sorafenib failure. Retrospective analysis of consecutive hepatocellular carcinoma patients receiving metronomic capecitabine between January 2012 and November 2014. The primary end-point was safety, secondary end-point was efficacy, including time-to-progression and overall survival. Twenty-six patients (80% Child-Pugh A, 80% Barcelona Clinic Liver Cancer stage C) received metronomic capecitabine (500 mg/bid). Median treatment duration was 3.2 months (range 0.6-31). Fourteen (53%) patients experienced at least one adverse event. The most frequent drug-related adverse events were bilirubin elevation (23%), fatigue (15%), anaemia (11%), lymphoedema (11%), and hand-foot syndrome (7.6%). Treatment was interrupted in 19 (73%) for disease progression, in 4 (15%) for liver deterioration, and in 1 (3.8%) for adverse event. Disease control was achieved in 6 (23%) patients. Median time-to-progression was 4 months (95% confidence interval 3.2-4.7). Median overall survival was 8 months (95% confidence interval 3.7-12.3). Metronomic capecitabine was well tolerated in hepatocellular carcinoma patients who had been treated with sorafenib. Preliminary data show potential anti-tumour activity with long-lasting disease control in a subgroup of patients that warrants further evaluation in a phase III study. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Combined treatment with D-allose, docetaxel and radiation inhibits the tumor growth in an in vivo model of head and neck cancer

    Science.gov (United States)

    Hoshikawa, Hiroshi; Kamitori, Kazuyo; Indo, Kanako; Mori, Terushige; Kamata, Mizuna; Takahashi, Tomoko; Tokuda, Masaaki

    2018-01-01

    The present study was designed to evaluate the effect of one rare sugar, D-allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D-allose in an in vivo model of head and neck cancer. Results indicated that D-allose did not inhibit the growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were observed after D-allose and D-glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-allose treatment increased by 2-fold (50.4 to 106.5). Conversely, the mRNA expression levels of TXNIP in HSC3 cancer cells increased by 74-fold (1.5 to 110.6), and the thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D-allose treatment. Combined multiple treatments with docetaxel, radiation and D-allose resulted in the greatest antitumor response in the in vivo model. Hyperkeratosis, epidermal thickening and tumor necrosis factor-α immunostaining were observed following irradiation treatment, but these pathophysiological reactions were reduced following D-allose administration. Thus, the present findings suggest that D-allose may enhance the antitumor effects of chemoradiotherapy whilst sparing normal tissues. PMID:29456721

  14. Treatment efficacy, treatment failures and selection of macrolide resistance in patients with high load of Mycoplasma genitalium during treatment of male urethritis with josamycin.

    Science.gov (United States)

    Guschin, Alexander; Ryzhikh, Pavel; Rumyantseva, Tatiana; Gomberg, Mikhail; Unemo, Magnus

    2015-02-03

    additional antimicrobials) and selection of macrolide resistance. Additional in vivo and in vitro data are crucial to support the recommendation of using josamycin as first-line treatment for M. genitalium infections in Russia. It would be valuable to develop international M. genitalium management guidelines, and quantitative diagnostic PCRs determining also M. genitalium load and resistance mutations (for macrolides and ideally also moxifloxacin) should ideally be recommended.

  15. [Acute renal failure in the transretinoic syndrome].

    Science.gov (United States)

    Sastre, A; Gago, E; Baños, M; Gómez, E

    2007-01-01

    The all-trans retinoic acid (ATRA) is the treatment of first line of acute promyelocytic leukemia (APL). ATRA is usually well tolerated, but a few major side effects can be observed, ATRA syndrome (RAS) being the most important of them, potentially fatal. The manifestations of this Syndrome are fever, weight gain, pulmonary infiltrates, pleural or pericardial effusions, hypotension, liver dysfunction and renal failure. We studied to the 29 patients diagnosed in (January of 2002 - December of 2004) of acute promyelocytic leukemia (APL), which were treated with ATRA, all received the 45 dose of mg/m(2)/d . The diagnosis of the leukemia was made by citomorphologist analysis. The criterion of renal insufficiency, it was an increase of the creatinina superior to 20% of the basal level. The definition of the transretinoico acid Syndrome was based on the clinical criteria of Frankel. Fourteen patients presented the Transretinoico Syndrome (48.3%), 11 of which (37.9%) died. The fundamental differences between the patients with or without ATRA were: fever (14 vs. 9, p=0,017), gain of weight (14 vs 0, p=0,000), pleural effusion (14 vs 2, p=0.000), pulmonary infiltrates (13 vs 1, p=0,000), cardiac failure (12 versus 2, p=0,000), respiratory distress (12 versus 4, p=0,003), presence of renal failure (10 vs 4, p=0,02), necessity of substitute renal treatment (6 vs 0, p=0,006) and arterial hypotension (12 vs. 3, p=0,001). The acute renal failure appeared in 10 of the 14 patients with SAR (71.4%), to 12+/-5 (1-25) days of the beginning of the treatment and their duration it was of 14+/-5 (1-46) days. Six (60%) needed substitute renal treatment and 5 (50%) died. Of the patients who survived, only a patient continues in dialysis. In both patient in that renal biopsy was made, the study showed signs of cortical necrosis. The appearance of acute renal failure in the course of the SAR is frequent, being observed deterioration of the renal function that needs substitute renal treatment

  16. Fasting cycles potentiate the efficacy of gemcitabine treatment in in vitro and in vivo pancreatic cancer models

    Science.gov (United States)

    Mazza, Tommaso; Panebianco, Concetta; Saracino, Chiara; Pereira, Stephen P.; Graziano, Paolo; Pazienza, Valerio

    2015-01-01

    Background/aims Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. Short-term fasting cycles have been shown to potentiate the efficacy of chemotherapy against glioma. The aim of this study was to assess the effect of fasting cycles on the efficacy of gemcitabine, a standard treatment for PC patients, in vitro and in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in standard and fasting mimicking culturing condition to evaluate the effects of gemcitabine. Pancreatic cancer xenograft mice were subjected to 24h starvation prior to gemcitabine injection to assess the tumor volume and weight as compared to mice fed ad libitum. Results Fasted pancreatic cancer cells showed increased levels of equilibrative nucleoside transporter (hENT1), the transporter of gemcitabine across the cell membrane, and decreased ribonucleotide reductase M1 (RRM1) levels as compared to those cultured in standard medium. Gemcitabine was more effective in inducing cell death on fasted cells as compared to controls. Consistently, xenograft pancreatic cancer mice subjected to fasting cycles prior to gemcitabine injection displayed a decrease of more than 40% in tumor growth. Conclusion Fasting cycles enhance gemcitabine effect in vitro and in the in vivo PC xenograft mouse model. These results suggest that restrictive dietary interventions could enhance the efficacy of existing cancer treatments in pancreatic cancer patients. PMID:26176887

  17. Effective treatment of chemoresistant breast cancer in vitro and in vivo by a factor VII-targeted photodynamic therapy.

    Science.gov (United States)

    Duanmu, J; Cheng, J; Xu, J; Booth, C J; Hu, Z

    2011-04-26

    The purpose of this study was to test a novel, dual tumour vascular endothelial cell (VEC)- and tumour cell-targeting factor VII-targeted Sn(IV) chlorin e6 photodynamic therapy (fVII-tPDT) by targeting a receptor tissue factor (TF) as an alternative treatment for chemoresistant breast cancer using a multidrug resistant (MDR) breast cancer line MCF-7/MDR. The TF expression by the MCF-7/MDR breast cancer cells and tumour VECs in MCF-7/MDR tumours from mice was determined separately by flow cytometry and immunohistochemistry using anti-human or anti-murine TF antibodies. The efficacy of fVII-tPDT was tested in vitro and in vivo and was compared with non-targeted PDT for treatment of chemoresistant breast cancer. The in vitro efficacy was determined by a non-clonogenic assay using crystal violet staining for monolayers, and apoptosis and necrosis were assayed to elucidate the underlying mechanisms. The in vivo efficacy of fVII-tPDT was determined in a nude mouse model of subcutaneous MCF-7/MDR tumour xenograft by measuring tumour volume. To our knowledge, this is the first presentation showing that TF was expressed on tumour VECs in chemoresistant breast tumours from mice. The in vitro efficacy of fVII-tPDT was 12-fold stronger than that of ntPDT for MCF-7/MDR cancer cells, and the mechanism of action involved induction of apoptosis and necrosis. Moreover, fVII-tPDT was effective and safe for the treatment of chemoresistant breast tumours in the nude mouse model. We conclude that fVII-tPDT is effective and safe for the treatment of chemoresistant breast cancer, presumably by simultaneously targeting both the tumour neovasculature and chemoresistant cancer cells. Thus, this dual-targeting fVII-tPDT could also have therapeutic potential for the treatment of other chemoresistant cancers.

  18. The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: a systematic review of the literature

    NARCIS (Netherlands)

    Berg, J. van den; Gordon, B.B.; Snijders, M.P.M.L.; Vandenbussche, F.P.H.A.; Coppus, S.F.P.J.

    2015-01-01

    OBJECTIVE(S): Early pregnancy failure (EPF) is a common complication of pregnancy. Surgical intervention carries a risk of complications and, therefore, medical treatment appears to be a safe alternative. Unfortunately, the current medical treatment with misoprostol alone has complete evacuation

  19. Functional imaging of the multidrug resistance in vivo

    International Nuclear Information System (INIS)

    Lee, Jae Tae

    2001-01-01

    Although diverse mechanisms are involved in multidrug resistance for chemotherapeutic drugs, the development of cellular P-glycoprotein(Pgp) and multidrug-resistance associated protein (MRP) are improtant factors in the chemotherapy failure to cancer. Various detection assays provide information about the presence of drug efflux pumps at the mRNA and protein levels. However these methods do not yield information about dynamic function of Pgp and MRP in vivo. Single photon emission tomograpy (SPECT) and positron emission tomograpy (PET) are available for the detection of Pgp and MRP-mediated transport. 99m Tc-sestaMIBI and other 99m Tc-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies of tumor imaging, and to visualize blockade of Pgp-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with 11 C have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and N- (11 C]acetyl-leukotriene E4 provides an opportunity to study MRP function non-invasively in vivo. Results obtained from recent publications are reviewed to confirm the feasibility of using SPECT and PET to study the functionality of MDR transportes in vivo

  20. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumor after failure with imatinib and sunitinib treatment: A meta-analysis.

    Science.gov (United States)

    Zhang, Zhenan; Jiang, Tao; Wang, Wensheng; Piao, Daxun

    2017-12-01

    This meta-analysis aimed to evaluate the safety and efficacy of regorafenib as a treatment for patients with advanced (metastatic and/or unresectable) gastrointestinal stromal tumor (AGIST) after developing resistance to imatinib and sunitinib. A literature search of databases such as PubMed, Embase, and Cochrane library was conducted up to February 2017. The pooled percentages and the corresponding 95% confidence intervals (CIs) were calculated using the Stata 11.0 software. Four studies involving 243 patients with AGIST were included. Results revealed that approximately 49% (95% CI 30-67), 14% (95% CI 5-23), and 41% (95% CI 21-61) of patients with AGIST showed clinical benefit (including complete response), partial response, and stable disease, respectively, after regorafenib treatment, which was given after failure with imatinib and sunitinib treatments. No complete response was found in the included studies. Pooled progression-free survival was 6.58 months (95% CI 4.62-8.54). Hypertension (20%; 95% CI 7-33), hand-foot skin reaction (22%; 95% CI 17-27), and hypophosphatemia (18%; 95% CI 5-41) were common grade ≥3 regorafenib-related adverse events in patients treated with regorafenib after failure with imatinib and sunitinib treatments. Forty-nine per cent of patients with AGIST benefited after regorafenib treatment after the development of resistance to imatinib and sunitinib. More studies should be performed to improve the clinical survival of patients with AGIST. Close monitoring and appropriate management of grade ≥3 regorafenib-related adverse events should be considered during treatment.

  1. Coordination failure caused by sunspots

    DEFF Research Database (Denmark)

    Beugnot, Julie; Gürgüç, Zeynep; Øvlisen, Frederik Roose

    2012-01-01

    on the efficient equilibrium, we consider sunspots as a potential reason for coordination failure. We conduct an experiment with a three player 2x2x2 game in which coordination on the efficient equilibrium is easy and should normally occur. In the control session, we find almost perfect coordination on the payoff......-dominant equilibrium, but in the sunspot treatment, dis-coordination is frequent. Sunspots lead to significant inefficiency, and we conclude that sunspots can indeed cause coordination failure....

  2. Effectivity of advanced wastewater treatment: reduction of in vitro endocrine activity and mutagenicity but not of in vivo reproductive toxicity.

    Science.gov (United States)

    Giebner, Sabrina; Ostermann, Sina; Straskraba, Susanne; Oetken, Matthias; Oehlmann, Jörg; Wagner, Martin

    2018-02-01

    Conventional wastewater treatment plants (WWTPs) have a limited capacity to eliminate micropollutants. One option to improve this is tertiary treatment. Accordingly, the WWTP Eriskirch at the German river Schussen has been upgraded with different combinations of ozonation, sand, and granulated activated carbon filtration. In this study, the removal of endocrine and genotoxic effects in vitro and reproductive toxicity in vivo was assessed in a 2-year long-term monitoring. All experiments were performed with aqueous and solid-phase extracted water samples. Untreated wastewater affected several endocrine endpoints in reporter gene assays. The conventional treatment removed the estrogenic and androgenic activity by 77 and 95 %, respectively. Nevertheless, high anti-estrogenic activities and reproductive toxicity persisted. All advanced treatment technologies further reduced the estrogenic activities by additional 69-86 % compared to conventional treatment, resulting in a complete removal of up to 97 %. In the Ames assay, we detected an ozone-induced mutagenicity, which was removed by subsequent filtration. This demonstrates that a post treatment to ozonation is needed to minimize toxic oxidative transformation products. In the reproduction test with the mudsnail Potamopyrgus antipodarum, a decreased number of embryos was observed for all wastewater samples. This indicates that reproductive toxicants were eliminated by neither the conventional nor the advanced treatment. Furthermore, aqueous samples showed higher anti-estrogenic and reproductive toxicity than extracted samples, indicating that the causative compounds are not extractable or were lost during extraction. This underlines the importance of the adequate handling of wastewater samples. Taken together, this study demonstrates that combinations of multiple advanced technologies reduce endocrine effects in vitro. However, they did not remove in vitro anti-estrogenicity and in vivo reproductive toxicity. This

  3. In vitro and in vivo evaluations of glass-ionomer cement containing chlorhexidine for Atraumatic Restorative Treatment

    Science.gov (United States)

    Duque, Cristiane; Aida, Kelly Limi; Pereira, Jesse Augusto; Teixeira, Gláucia Schuindt; Caldo-Teixeira, Angela Scarparo; Perrone, Luciana Rodrigues; Caiaffa, Karina Sampaio; Negrini, Thais de Cássia; de Castilho, Aline Rogéria Freire; Costa, Carlos Alberto de Souza

    2017-01-01

    Abstract Objectives: Addition of chlorhexidine has enhanced the antimicrobial effect of glass ionomer cement (GIC) indicated to Atraumatic Restorative Treatment (ART); however, the impact of this mixture on the properties of these materials and on the longevity of restorations must be investigated. The aim of this study was to evaluate the effects of incorporating chlorhexidine (CHX) in the in vitro biological and chemical-mechanical properties of GIC and in vivo clinical/ microbiological follow-up of the ART with GIC containing or not CHX. Material and Methods: For in vitro studies, groups were divided into GIC, GIC with 1.25% CHX, and GIC with 2.5% CHX. Antimicrobial activity of GIC was analyzed using agar diffusion and anti-biofilm assays. Cytotoxic effects, compressive tensile strength, microhardness and fluoride (F) release were also evaluated. A randomized controlled trial was conducted on 36 children that received ART either with GIC or GIC with CHX. Saliva and biofilm were collected for mutans streptococci (MS) counts and the survival rate of restorations was checked after 7 days, 3 months and one year after ART. ANOVA/Tukey or Kruskal-Wallis/ Mann-Whitney tests were performed for in vitro tests and in vivo microbiological analysis. The Kaplan-Meier method and Log rank tests were applied to estimate survival percentages of restorations (p<0.05). Results: Incorporation of 1.25% and 2.5% CHX improved the antimicrobial/anti-biofilm activity of GIC, without affecting F release and mechanical characteristics, but 2.5% CHX was cytotoxic. Survival rate of restorations using GIC with 1.25% CHX was similar to GIC. A significant reduction of MS levels was observed for KM+CHX group in children saliva and biofilm 7 days after treatment. Conclusions: The incorporation of 1.25% CHX increased the in vitro antimicrobial activity, without changing chemical-mechanical properties of GIC and odontoblast-like cell viability. This combination improved the in vivo short

  4. Non-invasive airway health assessment: Synchrotron imaging reveals effects of rehydrating treatments on mucociliary transit in-vivo

    Science.gov (United States)

    Donnelley, Martin; Morgan, Kaye S.; Siu, Karen K. W.; Farrow, Nigel R.; Stahr, Charlene S.; Boucher, Richard C.; Fouras, Andreas; Parsons, David W.

    2014-01-01

    To determine the efficacy of potential cystic fibrosis (CF) therapies we have developed a novel mucociliary transit (MCT) measurement that uses synchrotron phase contrast X-ray imaging (PCXI) to non-invasively measure the transit rate of individual micron-sized particles deposited into the airways of live mice. The aim of this study was to image changes in MCT produced by a rehydrating treatment based on hypertonic saline (HS), a current CF clinical treatment. Live mice received HS containing a long acting epithelial sodium channel blocker (P308); isotonic saline; or no treatment, using a nebuliser integrated within a small-animal ventilator circuit. Marker particle motion was tracked for 20 minutes using PCXI. There were statistically significant increases in MCT in the isotonic and HS-P308 groups. The ability to quantify in vivo changes in MCT may have utility in pre-clinical research studies designed to bring new genetic and pharmaceutical treatments for respiratory diseases into clinical trials.

  5. β-Arrestin2 Improves Post-Myocardial Infarction Heart Failure via Sarco(endo)plasmic Reticulum Ca2+-ATPase-Dependent Positive Inotropy in Cardiomyocytes.

    Science.gov (United States)

    McCrink, Katie A; Maning, Jennifer; Vu, Angela; Jafferjee, Malika; Marrero, Christine; Brill, Ava; Bathgate-Siryk, Ashley; Dabul, Samalia; Koch, Walter J; Lymperopoulos, Anastasios

    2017-11-01

    Heart failure is the leading cause of death in the Western world, and new and innovative treatments are needed. The GPCR (G protein-coupled receptor) adapter proteins βarr (β-arrestin)-1 and βarr-2 are functionally distinct in the heart. βarr1 is cardiotoxic, decreasing contractility by opposing β 1 AR (adrenergic receptor) signaling and promoting apoptosis/inflammation post-myocardial infarction (MI). Conversely, βarr2 inhibits apoptosis/inflammation post-MI but its effects on cardiac function are not well understood. Herein, we sought to investigate whether βarr2 actually increases cardiac contractility. Via proteomic investigations in transgenic mouse hearts and in H9c2 rat cardiomyocytes, we have uncovered that βarr2 directly interacts with SERCA2a (sarco[endo]plasmic reticulum Ca 2+ -ATPase) in vivo and in vitro in a β 1 AR-dependent manner. This interaction causes acute SERCA2a SUMO (small ubiquitin-like modifier)-ylation, increasing SERCA2a activity and thus, cardiac contractility. βarr1 lacks this effect. Moreover, βarr2 does not desensitize β 1 AR cAMP-dependent procontractile signaling in cardiomyocytes, again contrary to βarr1. In vivo, post-MI heart failure mice overexpressing cardiac βarr2 have markedly improved cardiac function, apoptosis, inflammation, and adverse remodeling markers, as well as increased SERCA2a SUMOylation, levels, and activity, compared with control animals. Notably, βarr2 is capable of ameliorating cardiac function and remodeling post-MI despite not increasing cardiac βAR number or cAMP levels in vivo. In conclusion, enhancement of cardiac βarr2 levels/signaling via cardiac-specific gene transfer augments cardiac function safely, that is, while attenuating post-MI remodeling. Thus, cardiac βarr2 gene transfer might be a novel, safe positive inotropic therapy for both acute and chronic post-MI heart failure. © 2017 American Heart Association, Inc.

  6. Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study

    OpenAIRE

    Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

    2017-01-01

    Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, People’s Republic of China Background: Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who resp...

  7. Ventilator-associated pneumonia in patients assisted by veno-arterial extracorporeal membrane oxygenation support: Epidemiology and risk factors of treatment failure.

    Science.gov (United States)

    Bouglé, Adrien; Bombled, Camille; Margetis, Dimitri; Lebreton, Guillaume; Vidal, Charles; Coroir, Marine; Hajage, David; Amour, Julien

    2018-01-01

    Ventilator-associated pneumonia (VAP) is frequent in Intensive Care Unit (ICU) patients. In the specific case of patients treated with Veno-Arterial Extracorporeal Membrane Oxygenation Support (VA-ECMO), VAP treatment failures (VAP-TF) have been incompletely investigated. To investigate the risk factors of treatment failure (VAP-TF) in a large cohort of ICU patients treated with VA-ECMO, we conducted a retrospective study in a Surgical ICU about patients assisted with VA-ECMO between January 1, 2013, and December 31, 2014. Diagnosis of VAP was confirmed by a positive quantitative culture of a respiratory sample. VAP-TF was defined as composite of death attributable to pneumonia and relapse within 28 days of the first episode. In total, 152 patients underwent ECMO support for > 48h. During the VA-ECMO support, 85 (55.9%) patients developed a VAP, for a rate of 60.6 per 1000 ECMO days. The main pathogens identified were Pseudomonas aeruginosa and Enterobacteriaceae. VAP-TF occurred in 37.2% of patients and was associated with an increased 28-day mortality (Hazard Ratio 3.05 [1.66; 5.63], P<0.001), and VA-ECMO assistance duration (HR 1.47 [1.05-2.05], P = 0.025). Risk factors for VAP-TF were renal replacement therapy (HR 13.05 [1.73; 98.56], P = 0.013) and documentation of Pseudomonas aeruginosa (HR 2.36 [1.04; 5.35], P = 0.04). VAP in patients treated with VA-ECMO is associated with an increased morbidity and mortality. RRT and infection by Pseudomonas aeruginosa appear as strong risks factors of treatment failure. Further studies seem necessary to precise the best antibiotic management in these patients.

  8. Heart failure and atrial fibrillation: current concepts and controversies.

    Science.gov (United States)

    Van den Berg, M. P.; Tuinenburg, A. E.; Crijns, H. J.; Van Gelder, I. C.; Gosselink, A. T.; Lie, K. I.

    1997-01-01

    Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases. PMID:9155607

  9. Antisense-MDM2 Sensitizes LNCaP Prostate Cancer Cells to Androgen Deprivation, Radiation, and the Combination In Vivo

    International Nuclear Information System (INIS)

    Stoyanova, Radka; Hachem, Paul; Hensley, Harvey; Khor, L.-Y.; Mu Zhaomei; Hammond, M. Elizabeth H.; Agrawal, Sudhir; Pollack, Alan

    2007-01-01

    Purpose: To test the effects of antisense (AS)-MDM2 alone and with androgen deprivation (AD), radiotherapy (RT), and AD + RT on wild-type LNCaP cells in an orthotopic in vivo model. Methods: Androgen-sensitive LNCaP cells were grown in the prostates of nude mice. Magnetic resonance imaging-based tumor volume and serum prostate-specific antigen (PSA) measurements were used to assess effects on tumor response. Tumor response was measured by biochemical and tumor volume failure definitions and doubling time estimates from fitted PSA and tumor volume growth curves. Expression of MDM2, p53, p21, and Ki-67 was quantified using immunohistochemical staining and image analysis of formalin-fixed tissue, analogous to methods used clinically. Results: Antisense-MDM2 significantly inhibited the growth of LNCaP tumors over the mismatch controls. The most significant increase in tumor growth delay and tumor doubling time was from AS-MDM2 + AD + RT, although the effect of AS-MDM2 + AD was substantial. Expression of MDM2 was significantly reduced by AS-MDM2 in the setting of RT. Conclusions: This is the first in vivo investigation of the effects of AS-MDM2 in an orthotopic model and the first to demonstrate incremental sensitization when added to AD and AD + RT. The results with AD underscore the potential to affect micrometastatic disease, which is probably responsible for treatment failure in 30-40% of men with high-risk disease

  10. Extracorporeal perfusion for the treatment of acute liver failure

    NARCIS (Netherlands)

    H.B.A.C. Stockmann; C.A. Hiemstra; R.L. Marquet (Richard); J.N.M. IJzermans (Jan)

    2000-01-01

    textabstractOBJECTIVE AND SUMMARY BACKGROUND DATA: Because of the shortage of available donor organs, death rates from liver failure remain high. Therefore, several temporary liver-assisting therapies have been developed. This article reviews various approaches to

  11. Atrial natriuretic factor binding sites in experimental congestive heart failure

    International Nuclear Information System (INIS)

    Bianchi, C.; Thibault, G.; Wrobel-Konrad, E.; De Lean, A.; Genest, J.; Cantin, M.

    1989-01-01

    A quantitative in vitro autoradiographic study was performed on the aorta, renal glomeruli, and adrenal cortex of cardiomyopathic hamsters in various stages of heart failure and correlated, in some instances, with in vivo autoradiography. The results indicate virtually no correlation between the degree of congestive heart failure and the density of 125I-labeled atrial natriuretic factor [(Ser99, Tyr126)ANF] binding sites (Bmax) in the tissues examined. Whereas the Bmax was increased in the thoracic aorta in moderate and severe heart failure, there were no significant changes in the zona glomerulosa. The renal glomeruli Bmax was lower in mild and moderate heart failure compared with control and severe heart failure. The proportion of ANF B- and C-receptors was also evaluated in sections of the aorta, adrenal, and kidney of control and cardiomyopathic hamsters with severe heart failure. (Arg102, Cys121)ANF [des-(Gln113, Ser114, Gly115, Leu116, Gly117) NH2] (C-ANF) at 10(-6) M displaced approximately 505 of (Ser99, Tyr126)125I-ANF bound in the aorta and renal glomeruli and approximately 20% in the adrenal zona glomerulosa in both series of animals. These results suggest that ANF may exert a buffering effect on the vasoconstriction of heart failure and to a certain extent may inhibit aldosterone secretion. The impairment of renal sodium excretion does not appear to be related to glomerular ANF binding sites at any stage of the disease

  12. Observation unit management of acute decompensated heart failure.

    Science.gov (United States)

    Schrock, Jon W; Emerman, Charles L

    2009-01-01

    Acute decompensated heart failure (ADHF) is a common illness presenting to the emergency department (ED) that is amenable to observation unit (OU) treatment. As the number of baby boomers continues to grow and the incidence of heart failure increases, the financial implications of ADHF treatment will become more prominent. Obtaining institutional support and developing a good working relationship with cardiology colleagues is vital to creating workable ADHF protocols for whichever type of OU an institution decides to use.

  13. EFFECTIVE TREATMENT OF PATIENTS WITH CHRONIC HEART FAILURE AND DEPRESSIVE DISORDERS WITH NOOTROPICS DRUG PANTOGAM ACTIV

    Directory of Open Access Journals (Sweden)

    A. P. Baranov

    2016-01-01

    Full Text Available We investigate the efficiency of the inclusion nootropic drug Pantogam Activ in the complex therapy of 82 patients with heart failure, ischemic heart diseases, anxiety and depressive disorders. It was shown that an 8-week treatment with Pantogam Activ in most patients is accompanied by a significant reduction of anxiety and depressive disorders, increase exercise tolerance, improved autonomic regulation of heart function and decrease the frequency of supraventricular and ventricular arrhythmias, which is accompanied by a marked improvement in the quality of life. 

  14. Impact of daily anatomical changes on EPID-based in vivo dosimetry of VMAT treatments of head-and-neck cancer

    International Nuclear Information System (INIS)

    Rozendaal, Roel A.; Mijnheer, Ben J.; Hamming-Vrieze, Olga; Mans, Anton; Herk, Marcel van

    2015-01-01

    Background and purpose: Target dose verification for VMAT treatments of head-and-neck (H&N) cancer using 3D in vivo EPID dosimetry is expected to be affected by daily anatomical changes. By including these anatomical changes through cone-beam CT (CBCT) information, the magnitude of this effect is investigated. Materials and methods: For 20 VMAT-treated H&N cancer patients, all plan-CTs (pCTs), 633 CBCTs and 1266 EPID movies were used to compare four dose distributions per fraction: treatment planning system (TPS) calculated dose and EPID reconstructed in vivo dose, both determined using the pCT and using the CBCT. D2, D50 and D98 of the planning target volume (PTV) were determined per dose distribution. Results: When including daily anatomical information, D2, D50 and D98 of the PTV change on average by 0.0 ± 0.4% according to TPS calculations; the standard deviation of the difference between EPID and TPS target dose changes from 2.5% (pCT) to 2.1% (CBCT). Small time trends are seen for both TPS and EPID dose distributions when using the pCT, which disappear when including CBCT information. Conclusions: Daily anatomical changes hardly influence the target dose distribution for H&N VMAT treatments according to TPS recalculations. Including CBCT information in EPID dose reconstructions slightly improves the agreement with TPS calculations

  15. Ex vivo inhibited cytokine profiling may explain inferior treatment response to golimumab after adalimumab failure in rheumatoid arthritis

    NARCIS (Netherlands)

    Tweehuysen, L; Schraa, K.; Netea, M.G.; Hoogen, F.H.J. van den; Joosten, L.A.B.; Broeder, A.A. den

    2018-01-01

    OBJECTIVES: Clinical data suggest that the response of rheumatoid arthritis patients to treatment with golimumab is much lower among those who switched from adalimumab than among those who switched from etanercept. To elucidate the mechanism behind this difference in response to sequential biologic

  16. Patterns of Failure After MammoSite Brachytherapy Partial Breast Irradiation: A Detailed Analysis

    International Nuclear Information System (INIS)

    Chen, Sea; Dickler, Adam; Kirk, Michael; Shah, Anand; Jokich, Peter; Solmos, Gene; Strauss, Jonathan; Dowlatshahi, Kambiz; Nguyen, Cam; Griem, Katherine

    2007-01-01

    Purpose: To report the results of a detailed analysis of treatment failures after MammoSite breast brachytherapy for partial breast irradiation from our single-institution experience. Methods and Materials: Between October 14, 2002 and October 23, 2006, 78 patients with early-stage breast cancer were treated with breast-conserving surgery and accelerated partial breast irradiation using the MammoSite brachytherapy applicator. We identified five treatment failures in the 70 patients with >6 months' follow-up. Pathologic data, breast imaging, and radiation treatment plans were reviewed. For in-breast failures more than 2 cm away from the original surgical bed, the doses delivered to the areas of recurrence by partial breast irradiation were calculated. Results: At a median follow-up time of 26.1 months, five treatment failures were identified. There were three in-breast failures more than 2 cm away from the original surgical bed, one failure directly adjacent to the original surgical bed, and one failure in the axilla with synchronous distant metastases. The crude failure rate was 7.1% (5 of 70), and the crude local failure rate was 5.7% (4 of 70). Estimated progression-free survival at 48 months was 89.8% (standard error 4.5%). Conclusions: Our case series of 70 patients with >6 months' follow-up and a median follow-up of 26 months is the largest single-institution report to date with detailed failure analysis associated with MammoSite brachytherapy. Our failure data emphasize the importance of patient selection when offering partial breast irradiation

  17. In vivo dosimetry in external beam radiotherapy

    International Nuclear Information System (INIS)

    Mijnheer, Ben; Beddar, Sam; Izewska, Joanna; Reft, Chester

    2013-01-01

    In vivo dosimetry (IVD) is in use in external beam radiotherapy (EBRT) to detect major errors, to assess clinically relevant differences between planned and delivered dose, to record dose received by individual patients, and to fulfill legal requirements. After discussing briefly the main characteristics of the most commonly applied IVD systems, the clinical experience of IVD during EBRT will be summarized. Advancement of the traditional aspects of in vivo dosimetry as well as the development of currently available and newly emerging noninterventional technologies are required for large-scale implementation of IVD in EBRT. These new technologies include the development of electronic portal imaging devices for 2D and 3D patient dosimetry during advanced treatment techniques, such as IMRT and VMAT, and the use of IVD in proton and ion radiotherapy by measuring the decay of radiation-induced radionuclides. In the final analysis, we will show in this Vision 20/20 paper that in addition to regulatory compliance and reimbursement issues, the rationale for in vivo measurements is to provide an accurate and independent verification of the overall treatment procedure. It will enable the identification of potential errors in dose calculation, data transfer, dose delivery, patient setup, and changes in patient anatomy. It is the authors’ opinion that all treatments with curative intent should be verified through in vivo dose measurements in combination with pretreatment checks

  18. In vivo dosimetry in external beam radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mijnheer, Ben [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam 1066 CX (Netherlands); Beddar, Sam [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Izewska, Joanna [Division of Human Health, International Atomic Energy Agency, Vienna 1400 (Austria); Reft, Chester [Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, Illinois 60637 (United States)

    2013-07-15

    In vivo dosimetry (IVD) is in use in external beam radiotherapy (EBRT) to detect major errors, to assess clinically relevant differences between planned and delivered dose, to record dose received by individual patients, and to fulfill legal requirements. After discussing briefly the main characteristics of the most commonly applied IVD systems, the clinical experience of IVD during EBRT will be summarized. Advancement of the traditional aspects of in vivo dosimetry as well as the development of currently available and newly emerging noninterventional technologies are required for large-scale implementation of IVD in EBRT. These new technologies include the development of electronic portal imaging devices for 2D and 3D patient dosimetry during advanced treatment techniques, such as IMRT and VMAT, and the use of IVD in proton and ion radiotherapy by measuring the decay of radiation-induced radionuclides. In the final analysis, we will show in this Vision 20/20 paper that in addition to regulatory compliance and reimbursement issues, the rationale for in vivo measurements is to provide an accurate and independent verification of the overall treatment procedure. It will enable the identification of potential errors in dose calculation, data transfer, dose delivery, patient setup, and changes in patient anatomy. It is the authors' opinion that all treatments with curative intent should be verified through in vivo dose measurements in combination with pretreatment checks.

  19. Predictive factors for renal failure and a control and treatment algorithm

    Directory of Open Access Journals (Sweden)

    Denise de Paula Cerqueira

    2014-04-01

    Full Text Available OBJECTIVES: to evaluate the renal function of patients in an intensive care unit, to identify the predisposing factors for the development of renal failure, and to develop an algorithm to help in the control of the disease.METHOD: exploratory, descriptive, prospective study with a quantitative approach.RESULTS: a total of 30 patients (75.0% were diagnosed with kidney failure and the main factors associated with this disease were: advanced age, systemic arterial hypertension, diabetes mellitus, lung diseases, and antibiotic use. Of these, 23 patients (76.6% showed a reduction in creatinine clearance in the first 24 hours of hospitalization.CONCLUSION: a decline in renal function was observed in a significant number of subjects, therefore, an algorithm was developed with the aim of helping in the control of renal failure in a practical and functional way.

  20. Safety Improvement in Radiotherapy Treatment Plan. Planning vs Redundant Check vs in vivo Dosimetry

    International Nuclear Information System (INIS)

    Torres Diaz, J.; Ascencion Ybarra, Y.; La Fuentes Rosales, L. de; Lara Mas, E.; Larrinaga Cortinas, E.

    2013-01-01

    In Cuba it is mandatory to have an independent monitor units check before any radiotherapy treatment is started. The main objective of this paper is to enhance the safety of the radiotherapy planning by developing and testing a practical tool to double check the monitor units calculation for external beam high energy photon therapy. A software for monitor units (MUs) verification was designed and coded. It considers the common in clinical practice isocentric set-ups. The in vivo dosimetry measurements were done with a silicon diode system for 6 MV photon beams to support the validation of the software. The results show a discrepancy within 5% between the 3 methods which is in accordance with international recommendations. (Author)

  1. Clinical application of in vivo treatment delivery verification based on PET/CT imaging of positron activity induced at high energy photon therapy

    Science.gov (United States)

    Janek Strååt, Sara; Andreassen, Björn; Jonsson, Cathrine; Noz, Marilyn E.; Maguire, Gerald Q., Jr.; Näfstadius, Peder; Näslund, Ingemar; Schoenahl, Frederic; Brahme, Anders

    2013-08-01

    The purpose of this study was to investigate in vivo verification of radiation treatment with high energy photon beams using PET/CT to image the induced positron activity. The measurements of the positron activation induced in a preoperative rectal cancer patient and a prostate cancer patient following 50 MV photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were delivered to the tumors. Imaging was performed with a 64-slice PET/CT scanner for 30 min, starting 7 min after the end of the treatment. The CT volume from the PET/CT and the treatment planning CT were coregistered by matching anatomical reference points in the patient. The treatment delivery was imaged in vivo based on the distribution of the induced positron emitters produced by photonuclear reactions in tissue mapped on to the associated dose distribution of the treatment plan. The results showed that spatial distribution of induced activity in both patients agreed well with the delivered beam portals of the treatment plans in the entrance subcutaneous fat regions but less so in blood and oxygen rich soft tissues. For the preoperative rectal cancer patient however, a 2 ± (0.5) cm misalignment was observed in the cranial-caud