WorldWideScience

Sample records for repeated intravenous dose

  1. Single and 2-week repeated intravenous dose toxicity studies of disodium mercaptoundecahydro-closo-dodecaborate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, Fumio; Yabuuchi, Kazuya; Ohno, Kouji; Muraoka, Yoshihiro [Shionogi and Co. Ltd., Toyonaka, Osaka (Japan). Developmental Research Lab.; Ikeuchi, Isao

    1998-10-01

    Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day. (author)

  2. Repeated intravenous doxapram induces phrenic motor facilitation.

    Science.gov (United States)

    Sandhu, M S; Lee, K Z; Gonzalez-Rothi, E J; Fuller, D D

    2013-12-01

    Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6mg/kg) or as a series of 3 injections (2mg/kg) at 5min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2mg/kg. At 60min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (Pphrenic response to doxapram (2mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury. © 2013.

  3. [Toxicity studies of landiolol hydrochloride (ONO-1101) (2). 4-week repeated dose intravenous toxicity study in rats with 4-week recovery test].

    Science.gov (United States)

    Yamaguchi, K; Yanagi, H; Shimizu, K; Sakai, M; Nishibata, K; Oida, H; Shinomiya, K; Suzuki, Y; Yonezawa, H; Fujita, T

    1997-12-01

    4-week repeated dose toxicity study with 4-week recovery test of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in Sprague-Dawley (SD) rats. ONO-1101 was administered intravenously to rats of both sexes at a dose level of 0 (control), 12.5, 25, 50 or 100 mg/kg/day. In the 100 mg/kg/day group, bradypnea or dyspnea was seen in all animals, pale in ear, eye and foot, tremor, reddish lacrimation and loss of righting reflex were also observed in some animals right after administration, and then those signs disappeared within 1 min after administration. During the treatment period, 3/20 animals of each sex in the 100 mg/kg/day showed clonic convulsion and died within 2 min after administration. No clinical changes were seen in the 50 mg/kg/day group or lower. Histopathological findings showed atrophy of the submaxillary gland in females and vessel-wall thickening and perivascular fibrosis of the injection site (tail) in both sexes at 100 mg/kg/day, however those changes were reversible. ONO-1101 did not effect on body weight, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weights or necropsy at any doses. These results indicate that the no-adverse-effect level of ONO-1101 in rats is 50 mg/kg/day for both sexes in this study.

  4. Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study.

    Science.gov (United States)

    Zhang, Ting; Tang, Meng; Zhang, Shanshan; Hu, Yuanyuan; Li, Han; Zhang, Tao; Xue, Yuying; Pu, Yuepu

    2017-01-01

    The numerous increasing use of carbon nanotubes (CNTs) derived from nanotechnology has raised concerns about their biosafety and potential toxicity. CNTs cause immunologic dysfunction and limit the application of CNTs in biomedicine. The immunological responses induced by pristine multi-walled carbon nanotubes (p-MWCNTs) and PEGylated multi-walled carbon nanotubes (MWCNTs-PEG) on BALB/c mice via an intravenous administration were investigated. The results reflect that the p-MWCNTs induced significant increases in spleen, thymus, and lung weight. Mice treated with p-MWCNTs showed altered lymphocyte populations (CD3 + , CD4 + , CD8 + , and CD19 + ) in peripheral blood and increased serum IgM and IgG levels, and splenic macrophage ultrastructure indicated mitochondria swelling. p-MWCNTs inhibited humoral and cellular immunity function and were associated with decreased immune responses against sheep erythrocytes and serum hemolysis level. Natural killer (NK) activity was not modified by two types of MWCNTs. In comparison with two types of MWCNTs, for a same dose, p-MWCNTs caused higher levels of inflammation and immunosuppression than MWCNTs-PEG. The results of immunological function suggested that after intravenous administration with p-MWCNTs caused more damage to systemic immunity than MWCNTs-PEG. Here, we demonstrated that a surface functional modification on MWCNTs reduces their immune perturbations in vivo. The chemistry-modified MWCNTs change their preferred immune response in vivo and reduce the immunotoxicity of p-MWCNTs.

  5. Radiation dose measurements in intravenous pyelography

    International Nuclear Information System (INIS)

    Egeblad, M.; Gottlieb, E.

    1975-01-01

    Intravenous pyelography (IVP) and micturition cystourethrography (MCU) are the standard procedures in the radiological examination of children with urinary tract infections and in the control of these children. Gonad protection against radiation is not possible in MCU, but concerning the girls partly possible in IVP. It is of major importance to know the radiation dose in these procedures, especially since the examination is often repeated in the same patients. All IVP were done by means of the usual technique including possible gonad protection. The thermoluminescence dosimeter was placed rectally in the girls and fixed on the scrota in the boys. A total of 50 children was studied. Gonad dose ranged from 140 to 200mR in the girls and from 20 to 70mR in the boys (mean values). The radiation dose in IVP is very low compared to that of MCU, and from this point of view IVP is a dose saving examination in the control of children with urinary tract infections [fr

  6. Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

    Directory of Open Access Journals (Sweden)

    Zhang T

    2017-02-01

    Full Text Available Ting Zhang,1–3 Meng Tang,1–3 Shanshan Zhang,1–3 Yuanyuan Hu,1–3 Han Li,4 Tao Zhang,4 Yuying Xue,1–3 Yuepu Pu1–3 1Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China; 2Jiangsu key Laboratory for Biomaterials and Devices, Southeast University, Nanjing, China; 3Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou, China; 4Department of Material Science and Engineering, National Key Laboratory of Solid State Microstructures, Nanjing University, Nanjing, China Abstract: The numerous increasing use of carbon nanotubes (CNTs derived from nanotechnology has raised concerns about their biosafety and potential toxicity. CNTs cause immunologic dysfunction and limit the application of CNTs in biomedicine. The immunological responses induced by pristine multi-walled carbon nanotubes (p-MWCNTs and PEGylated multi-walled carbon nanotubes (MWCNTs-PEG on BALB/c mice via an intravenous administration were investigated. The results reflect that the p-MWCNTs induced significant increases in spleen, thymus, and lung weight. Mice treated with p-MWCNTs showed altered lymphocyte populations (CD3+, CD4+, CD8+, and CD19+ in peripheral blood and increased serum IgM and IgG levels, and splenic macrophage ultrastructure indicated mitochondria swelling. p-MWCNTs inhibited humoral and cellular immunity function and were associated with decreased immune responses against sheep erythrocytes and serum hemolysis level. Natural killer (NK activity was not modified by two types of MWCNTs. In comparison with two types of MWCNTs, for a same dose, p-MWCNTs caused higher levels of inflammation and immunosuppression than MWCNTs-PEG. The results of immunological function suggested that after intravenous administration with p-MWCNTs caused more damage to systemic immunity than MWCNTs- PEG. Here, we demonstrated that a surface functional modification on MWCNTs reduces

  7. Low-dose intravenous lidocaine as treatment for proctalgia fugax.

    Science.gov (United States)

    Peleg, Roni; Shvartzman, Pesach

    2002-01-01

    Proctalgia fugax is characterized by a sudden internal anal sphincter and anorectic ring attack of pain of a short duration. Description of the influence of intravenous lidocaine treatment for proctalgia fugax. A 28-year-old patient suffering of proctalgia fugax for 8 months. Conventional treatment efforts did not improve his condition. A single dose of an intravenous lidocaine infusion completely stopped his pain attacks. Based on the experience reported in this case and the potential benefit of this treatment for proctalgia fugax, controlled studies comparing intravenous lidocaine with placebo should be conducted to confirm the observation and to provide a more concrete basis for the use of intravenous lidocaine for this indication.

  8. Influence of intravenous opioid dose on postoperative ileus.

    Science.gov (United States)

    Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J

    2011-07-01

    Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain management options when this occurs.

  9. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie

    2016-01-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

  10. Radiation Doses in Intravenous Urography And Potentials For Optimization

    International Nuclear Information System (INIS)

    Halato, M.A.; Badawi, A.; Gassom, G.A.; Barsham, M.A.; Ibrahim, A.F.; Suliman, I.I.; Sulieman, A.A.

    2011-01-01

    In this study radiation doses in IVU clinical examinations were measured in three public hospitals and a sample of 44 patients. In each room the machine output was measured for different peak tube voltages. Patient's data such as (age and weight) and exposure parameters (kVp) and mAs) were recorded. Entrance Surface Air Kerma (ESAK) for patients was determined by using the tube output and the patient exposure parameters. The ESAK ranged from 0.76 to 6.75 mGy. The cumulative ESAK ranged from 3.5 to 34.6 mGy. In conclusion, the obtained results are in agreement with the standard reference ESAK levels. The study showed that the cumulative ESAK can approach a level known to increase the probability of stochastic effect. Keywords: Patient dose, intravenous Urography, radiation protection

  11. Antithrombotic effect of repeated doses of the ethanolic extract of ...

    African Journals Online (AJOL)

    Antithrombotic effect of repeated doses of the ethanolic extract of local olive ( Olea europaea L.) leaves in rabbits. ... The incidence of thromboembolic diseases is increasing, and they are a major cause of mortality and morbidity worldwide. Mediterranean diet is known for its high content of olive products, especially olive oil, ...

  12. Impact of repeated intravenous cocaine administration on incentive motivation depends on mode of drug delivery.

    Science.gov (United States)

    LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

    2014-11-01

    The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug's long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking. © 2013 Society for the Study of Addiction.

  13. Inversion-based propofol dosing for intravenous induction of hypnosis

    Science.gov (United States)

    Padula, F.; Ionescu, C.; Latronico, N.; Paltenghi, M.; Visioli, A.; Vivacqua, G.

    2016-10-01

    In this paper we propose an inversion-based methodology for the computation of a feedforward action for the propofol intravenous administration during the induction of hypnosis in general anesthesia. In particular, the typical initial bolus is substituted with a command signal that is obtained by predefining a desired output and by applying an input-output inversion procedure. The robustness of the method has been tested by considering a set of patients with different model parameters, which is representative of a large population.

  14. Treatment of early AIDS dementia in intravenous drug users : High versus low dose peptide T

    NARCIS (Netherlands)

    Kosten, TR; Rosen, MI; McMahon, TL; Bridge, TP; OMalley, SS; Pearsall, R; OConnor, PG

    1997-01-01

    This placebo-controlled, double blind, cross-over study tested the efficacy of two different doses of Peptide T in the treatment of nine intravenous drug users with early AIDS dementia who were also receiving methadone and AZT. Subjects received Peptide T doses of either 15 or 1.5 mg daily for four

  15. Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, C; Thomsen, L L; Norgaard, A

    2017-01-01

    BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, ran......BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open...

  16. Pharmacology of ayahuasca administered in two repeated doses.

    Science.gov (United States)

    Dos Santos, Rafael G; Grasa, Eva; Valle, Marta; Ballester, Maria Rosa; Bouso, José Carlos; Nomdedéu, Josep F; Homs, Rosa; Barbanoj, Manel J; Riba, Jordi

    2012-02-01

    Ayahuasca is an Amazonian tea containing the natural psychedelic 5-HT(2A/2C/1A) agonist N,N-dimethyltryptamine (DMT). It is used in ceremonial contexts for its visionary properties. The human pharmacology of ayahuasca has been well characterized following its administration in single doses. To evaluate the human pharmacology of ayahuasca in repeated doses and assess the potential occurrence of acute tolerance or sensitization. In a double-blind, crossover, placebo-controlled clinical trial, nine experienced psychedelic drug users received PO the two following treatment combinations at least 1 week apart: (a) a lactose placebo and then, 4 h later, an ayahuasca dose; and (b) two ayahuasca doses 4 h apart. All ayahuasca doses were freeze-dried Amazonian-sourced tea encapsulated to a standardized 0.75 mg DMT/kg bodyweight. Subjective, neurophysiological, cardiovascular, autonomic, neuroendocrine, and cell immunity measures were obtained before and at regular time intervals until 12 h after first dose administration. DMT plasma concentrations, scores in subjective and neurophysiological variables, and serum prolactin and cortisol were significantly higher after two consecutive doses. When effects were standardized by plasma DMT concentrations, no differences were observed for subjective, neurophysiological, autonomic, or immunological effects. However, we observed a trend to reduced systolic blood pressure and heart rate, and a significant decrease for growth hormone (GH) after the second ayahuasca dose. Whereas there was no clear-cut tolerance or sensitization in the psychological sphere or most physiological variables, a trend to lower cardiovascular activation was observed, together with significant tolerance to GH secretion.

  17. Quantitative MR changes in Gd-DTPA enhancement after high dose intravenous methylprednisolone in multiple sclerosis

    International Nuclear Information System (INIS)

    Barkhof, F.; Valk, J.; Hommes, O.R.; Scheltens, P.

    1991-01-01

    The purpose of this study was to investigate the effect of high dose intravenous methylprednisolone (MP) on gadolinium-DTPA enhancement in MS-lesions. By means of this the influence of MP on the permeability of the blood-brain barrier can be studied. (author). 19 refs.; 1 fig

  18. Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Christiansen, I; Harbo, Thomas

    2014-01-01

    High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...

  19. Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

    OpenAIRE

    Motov, Sergey; Drapkin, Jefferson; Likourezos, Antonios; Beals, Tyler; Monfort, Ralph; Fromm, Christian; Marshall, John

    2018-01-01

    Introduction: Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK) infusion for managing a variety of painful conditions in the emergency department (ED).  Methods: We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a pe...

  20. Intravenous high-dose immunotherapy: practical recommendations for use in the treatment of neurological disimmune diseases

    Directory of Open Access Journals (Sweden)

    N. A. Suponeva

    2015-01-01

    Full Text Available Current publication summarizes main indications and benefits of intravenous high-dose immunotherapy (IHI in the treatment of various autoimmune diseases of the peripheral nervous system. Available products of intravenous immunoglobulin (IVIG on the Russian market are reviewed. Tactics for choosing optimal medication for IHI based on its effectiveness and safety are analyzed. Dosage calculation and way of administration of IVIG are described, beeing of a high practical value in neurologist’s daily work.

  1. Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants.

    Science.gov (United States)

    Tekgündüz, Kadir Şerafettin; Ceviz, Naci; Caner, İbrahim; Olgun, Haşim; Demirelli, Yaşar; Yolcu, Canan; Şahin, İrfan Oğuz; Kara, Mustafa

    2015-08-01

    Haemodynamically significant patent ductus arteriosus is a significant cause of morbidity and mortality in pre-term infants. This retrospective study was conducted to investigate the usefulness of lower-dose paracetamol for the treatment of patent ductus arteriosus in pre-term infants. A total of 13 pre-term infants who received intravenous paracetamol because of contrindications or side effects to oral ibuprofen were retrospectively enrolled. In the first patient, the dose regimen was 15 mg/kg/dose, every 6 hours. As the patient developed significant elevation in transaminase levels, the dose was decreased to 10 mg/kg/dose, every 8 hours in the following 12 patients. Echocardiographic examination was conducted daily. In case of closure, it was repeated after 2 days and when needed thereafter in terms of reopening. A total of 13 patients received intravenous paracetamol. Median gestational age was 29 weeks ranging from 24 to 31 weeks and birth weight was 950 g ranging from 470 to 1390 g. The median postnatal age at the first intravenous paracetamol dose was 3 days ranging from 2 to 9 days. In 10 of the 13 patients (76.9%), patent ductus arteriosus was closed at the median 2nd day of intravenous paracetamol ranging from 1 to 4 days. When the patient who developed hepatotoxicity was eliminated, the closure rate was found to be 83.3% (10/12). Intravenous paracetamol may be a useful treatment option for the treatment of patent ductus arteriosus in pre-term infants with contrindication to ibuprofen. In our experience, lower-dose paracetamol is effective in closing the patent ductus arteriosus in 83.3% of the cases.

  2. Dose-ranging pharmacokinetics of colistin methanesulphonate (CMS) and colistin in rats following single intravenous CMS doses.

    Science.gov (United States)

    Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William

    2010-08-01

    The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.

  3. Repeated Intra-Arterial Thrombectomy within 72 Hours in a Patient with a Clear Contraindication for Intravenous Thrombolysis

    Directory of Open Access Journals (Sweden)

    Mona Laible

    2015-01-01

    Full Text Available Introduction. Treating patients with acute ischemic stroke, proximal arterial vessel occlusion, and absolute contraindication for administering intravenous recombinant tissue plasminogen activator (rtPA poses a therapeutic challenge. Intra-arterial thrombectomy constitutes an alternative treatment option. Materials and Methods. We report a case of a 57-year-old patient with concomitant gastric adenocarcinoma, who received three intra-arterial thrombectomies in 72 hours due to repeated occlusion of the left medial cerebral artery (MCA. Findings. Intra-arterial recanalization of the left medial cerebral artery was performed three times with initially good success. However, two days later, the right medial cerebral artery became occluded. Owing to the overall poor prognosis at that time and knowing the wishes of the patient, we decided not to perform another intra-arterial recanalization procedure. Conclusion. To our knowledge, this is the first case illustrating the use of repeated intra-arterial recanalization in early reocclusion of intracranial vessels.

  4. Prophylactic CNS therapy in childhood leukemia. Randomized controlled study of high-dose intravenous methotrexate and cranial irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Takashi; Hiyoshi, Yasuhiko [Kurume Univ., Fukuoka (Japan). School of Medicine; Fujimoto, Takeo

    1982-12-01

    This study was designed to evaluate the efficacy of CNS-prophylaxis with high-dose methotrexate (MTX). Seventy children with previously untreated acute lymphoblastic leukemia (ALL) entered to this study between July 1978 and December 1980. According to initial white blood count (WBC), they were stratified to induce remission with; vincristine and prednine in low initial WBC ( lt 25,000/mm/sup 3/) group and these two agents plus adriamycin in high initial WBC ( gt 25,000/mm/sup 3/) group. After inducing remission, 62 children who achieved CR, received different CNS-prophlaxis; using a regimen of three doses of weekly high-dose MTX (1,000 mg/m/sup 2/) 6-hour infusion, which was repeated every 12 weeks-Group A (n = 14); high-dose MTX followed by 2400 rad cranial irradiation plus three doses of i.t. MT X-Group B (n = 15), 2400 rad cranial irradiation plus three doses of i.t. MTX-Group C (n = 16), and in 17 patients with high initial WBC, same as in Group A-Group D (n = 17). During an intravenous 6-h infusion of MTX at a dose of 1,000 mg/m/sup 2/, the CSF concentration of MTX rose to 2.3 +- 2.4 x 10/sup -6/M after initiation of infusion and remained in 10/sup -7/ M level for 48 hours. CNS-leukemia terminated complete remission in one of 14 children in Group A, two of 15 in Group B, two of 16 in Group C and two of 17 in Group D. The cumulative incidence of CNS-leukemia at 20 months calculated by the technique of Kaplan and Meier was 0% in Group A, 18.1% in Group B, 7.1% in Group C and 50.8% in Group D. There was no statistical difference among Groups A, B and C. These data suggested that CNS-prophylaxis with high-dose intravenous MTX was effective as well as 2400 rad cranial irradiation plus three doses of i.t. MTX in childhood ALL with low initial WBC.

  5. Absorbed Doses to Embryo from Intravenous Urography at Selected Radiological Departments in Slovakia

    International Nuclear Information System (INIS)

    Karkus, R.; Nikodemova, D.; Horvathova, M.

    2003-01-01

    Actual legislation used in radiological protection requires quality assurance program for decreasing radiation load of patients from radiological examinations. The information about irradiation of pregnant women is very important, because the embryo is more radiosensitive as adult organism. On the basis of absence of unified calculations or measurements of absorbed doses to embryo from various radiological examinations in Slovakia we present in this study the values of absorbed doses to embryo from intravenous urography at selected radiological departments in Slovakia. Absorbed doses to embryo were obtained by measurement and calculation using the simulation of irradiation of pregnant woman by intravenous urography. The results of our study indicate, that absorbed doses to embryo were at various radiological departments considerably different, depending on type of X-ray machine and different settings of technical parameters of X-ray machine. In accordance with worldwide trend it is necessary to decrease radiation load of patients as low as possible level. Differences in radiation load between radiological departments indicate, that it is necessary to continue in solving of this problem and perform measurements and calculations of absorbed doses to embryo at different types of X-ray machines and at different examinations, where the embryo is in direct beam of X-ray. (author)

  6. The effects of repeated low-dose sarin exposure

    International Nuclear Information System (INIS)

    Shih, T.-M.; Hulet, S.W.; McDonough, J.H.

    2006-01-01

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD 5 dose of sarin (42 μg/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection. No guinea pig receiving 0.3, 0.4 or 0.5 x LD 5 of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD 5 of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD 5 sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD 5 sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD 5 sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD 5 sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving the 0.4 and 0.5 x LD 5 doses of sarin failed to

  7. Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.

    Science.gov (United States)

    Mermelstein, Fred; Hamilton, Douglas A; Wright, Curtis; Lacouture, Peter G; Ramaiya, Atulkumar; Carr, Daniel B

    2013-10-01

    To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. Clinical research center. Healthy adult volunteers. Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HP

  8. Randomized controlled trial comparing different single doses of intravenous paracetamol for placement of peripherally inserted central catheters in preterm infants

    NARCIS (Netherlands)

    D.W.E. Roofthooft (Daniella); S.H. Simons (Sinno); R.A. Lingen (Richard); D. Tibboel (Dick); J.N. van den Anker (John); I.K.M. Reiss (Irwin); M. van Dijk (Monique)

    2017-01-01

    markdownabstract__Background:__ The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different

  9. Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Jefferson Drapkin

    2018-03-01

    Full Text Available Introduction: Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK infusion for managing a variety of painful conditions in the emergency department (ED. Methods: We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a period over six years (2010–2016. Primary data analyses included dosing and duration of infusion, rates of pre- and post-infusion analgesic administration, and final diagnoses. Secondary data included pre- and post-infusion pain scores and rates of side effects. Results: A total of 104 patients were enrolled in the study. Average dosing of SDK infusion was 11.26 mg/hr, and the mean duration of infusion was 135.87 minutes. There was a 38% increase in patients not requiring post-infusion analgesia. The average decrease in pain score was 5.04. There were 12 reported adverse effects, with nausea being the most prevalent. Conclusion: Continuous intravenous SDK infusion has a role in controlling pain of various etiologies in the ED with a potential to reduce the need for co-analgesics or rescue analgesic administration. There is a need for more robust, prospective, randomized trials that will further evaluate the analgesic efficacy and safety of this modality across a wide range of pain syndromes and different age groups in the ED.

  10. Saving radiation dose and contrast media in intravenous digital subtraction angiography by use of bolus chasing

    International Nuclear Information System (INIS)

    Rueckforth, J.; Schuermann, K.; Vorwerk, D.; Guenther, R.W.

    1998-01-01

    Purpose: This study evaluates the dose area product, the amount of contrast media and the examination quality of the bolus chasing technique compared to the single-step technique in intravenous digital subtraction angiography. Material and Methods: 15 examinations each with bolus chasing and single-step technique were compared. The dose area product and the volume of contrast media were recorded. The examination quality was scored by two examiners. Results: With bolus chasing the volume of the administered contrast media could be decreased on average by 114 ml (43%). The difference between the dose area product of bolus chasing (722 dGy/cm 2 ) and single-step technique (1910 dGy/cm 2 ) was significant. No significant difference in examination quality was found. Conclusions: The intravenous bolus chasing technique is a practicable method. Compared to the single-step technique it allows a remarkable dose reduction and a low consumption of contrast media without restriction of examination quality. (orig.) [de

  11. Evaluating the potential of gold, silver, and silica nanoparticles to saturate mononuclear phagocytic system tissues under repeat dosing conditions.

    Science.gov (United States)

    Weaver, James L; Tobin, Grainne A; Ingle, Taylor; Bancos, Simona; Stevens, David; Rouse, Rodney; Howard, Kristina E; Goodwin, David; Knapton, Alan; Li, Xiaohong; Shea, Katherine; Stewart, Sharron; Xu, Lin; Goering, Peter L; Zhang, Qin; Howard, Paul C; Collins, Jessie; Khan, Saeed; Sung, Kidon; Tyner, Katherine M

    2017-07-17

    As nanoparticles (NPs) become more prevalent in the pharmaceutical industry, questions have arisen from both industry and regulatory stakeholders about the long term effects of these materials. This study was designed to evaluate whether gold (10 nm), silver (50 nm), or silica (10 nm) nanoparticles administered intravenously to mice for up to 8 weeks at doses known to be sub-toxic (non-toxic at single acute or repeat dosing levels) and clinically relevant could produce significant bioaccumulation in liver and spleen macrophages. Repeated dosing with gold, silver, and silica nanoparticles did not saturate bioaccumulation in liver or spleen macrophages. While no toxicity was observed with gold and silver nanoparticles throughout the 8 week experiment, some effects including histopathological and serum chemistry changes were observed with silica nanoparticles starting at week 3. No major changes in the splenocyte population were observed during the study for any of the nanoparticles tested. The clinical impact of these changes is unclear but suggests that the mononuclear phagocytic system is able to handle repeated doses of nanoparticles.

  12. The incidence of phlebitis with intravenous amiodarone at guideline dose recommendations.

    Science.gov (United States)

    Slim, Ahmad M; Roth, Jason E; Duffy, Benjamin; Boyd, Sheri Y N; Rubal, Bernard J

    2007-12-01

    Postoperative atrial fibrillation following cardiothoracic surgery is common and frequently managed with intravenous (IV) amiodarone. Phlebitis is the most common complication with peripheral infusion of this agent. Current practice guidelines for peripheral IV administration of phlebitis. The present study examines the incidence of phlebitis in a postoperative patient population given current dose recommendations. A total of 273 patient charts were reviewed. The incidence of phlebitis in patients given IV amiodarone (n = 36) was 13.9% (95% confidence interval, 2.6-25.2%; p = 0.001). Logistic regression analysis with backward elimination of other therapeutic risk factors suggests that the odds ratio for phlebitis using current dose regimens without IV filters is 19-fold greater than baseline risk in this population. Phlebitis remains a significant complication associated with peripheral infusion of amiodarone within recommended dosing limits.

  13. Distribution and excretion after intravenous dosing of [{sup 14}C]micafungin to rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamato, Yasuhiro; Kaneko, Hayato; Yamasaki, Sachiko; Fujiwara, Tomoichi; Katashima, Masataka; Kawamura, Akio; Terakawa, Masato; Kagayama, Akira [Fujisawa Pharmaceutical Co., Ltd., Osaka (Japan). Biopharmaceutical and Pharmacokinetic Research Lab.

    2002-12-01

    In this study, distribution and excretion after intravenous dosing of [{sup 14}C] micafungin (1 mg/kg) to rats and in vitro serum protein binding and distribution to blood cells in mouse, rat, dog and human were investigated. The concentration of radioactivity in plasma at 5 min, which was the first observation point, was 3,396 ng eq./mL and decreased triexponentially. At 24 h, the concentration had decreased to approximately 12.4% of that at 5 min, and thereafter it deceased with a half-time of 39.3 h. The blood to plasma radioactivity concentration ratios were in the range of 0.80 to 1.00 for up to 7 day after dosing, and were 1.00 or more thereafter. The radioactivity was widely distributed immediately after dosing. The highest radioactivity concentrations were observed in the lungs at 5 min and were 1.86 times higher than that in plasma, followed by the kidneys (1.09). The relative radioactivity concentrations in brain, eyeball, white fat and testis were less than 0.08 of that in plasma, and those in other tissues were in the range of 0.17 to 0.86. The radioactivity concentrations in all tissues examined at 24 h had decreased compared with those at 5 min or 6 h, and decreased almost in parallel with plasma radioactivity concentrations from 72 h with the exception of concentrations for white fat. Up to 240 h after intravenous dosing, 83.5% and 14.4% of the radioactivity had been excreted in feces and urine, respectively. At 240 h, 2.8% and 0.3% of the radioactivity were detected in carcass and gut, respectively. In the expired air, no radioactivity was detected up to 72 h. Up to 48 h after intravenous dosing, 43.9%, 13.2% and 8.3% of the radioactivity had been excreted in bile, urine and feces, respectively. At 48 h, 32.2% and 4.4% of radioactivity were detected in carcass and gut, respectively. (author)

  14. Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations

    Directory of Open Access Journals (Sweden)

    Todd A. Koch

    2015-01-01

    Full Text Available Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA, we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7, we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM to 1000 mg iron sucrose (IS. Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1–5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p<0.001 lower (5.6% in the 1500 mg group, compared to the 1000 mg group (11.1%. Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients.

  15. Dose-dependent effects of intravenous lorazepam on cardiovascular activity, plasma catecholamines and psychological function during rest and mental stress

    NARCIS (Netherlands)

    J.H.M. Tulen (Joke); P. Moleman (Peter); F. Boomsma (Frans); H.G. van Steenis (H.); V.J.H.M. van den Heuij (Venantius)

    1991-01-01

    textabstractDose-dependent effects of intravenously administered lorazepam on psychophysiological activity during rest and mental stress were studied in order to examine differential responses to doses which may induce anxiolysis or sedation. In a double-blind randomized cross-over study, nine male

  16. Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab.

    Science.gov (United States)

    Ehrenpreis, Eli D

    2017-12-01

    Infliximab pharmacokinetic studies have been performed in patients receiving chronic infliximab therapy. In these patients, infliximab antidrug antibodies (ADAs) increase infliximab clearance and decrease serum levels and drug efficacy. This study analyzed the pharmacokinetic effect of infliximab ADAs in healthy subjects receiving a single dose of intravenous infliximab. Data were obtained from a single-blind, parallel-group, single-dose study of healthy subjects receiving 5 mg/kg of intravenous SB2 (infliximab biosimilar), EU-sourced Remicade (EU-IFX) or US-sourced Remicade (US-IFX). Serum infliximab was measured at 1, 2, 3, 6, 12, 24, 48, and 72 h and at 5, 7, 14, 21, 28, 42, 56, and 70 days after administration. ADAs were measured pre-dose and at 29 and 71 days. Data from the first ten subjects randomized to each treatment arm were utilized for this study. A two-compartment model of the serum infliximab vs. time curve was developed using nonlinear regression. At 10 weeks, 11 subjects (37%) developed ADAs. ADAs were detected in four subjects after SB2, one subject after EU-IFX, and six subjects after US-IFX infusion. Of these, neutralizing antibodies occurred in one subject after SB2, in no subjects after EU-IFX, and in three subjects after US-IFX infusion. Infliximab clearance was increased in subjects with ADAs vs. those without ADAs (12.89 ± 2.69 vs. 9.90 ± 1.74 ml/h; p ADAs (282.4 ± 56.4 vs. 343.3 ± 61.9 h; p ADAs are common in healthy subjects after a single intravenous dose of infliximab and result in faster infliximab clearance, shorter elimination time, and lower serum infliximab levels. These data confirm that ADAs are common with biologic therapy and significantly impact the efficacy of these drugs.

  17. Pharmacokinetics of colistin methanesulfonate (CMS) in healthy Chinese subjects after single and multiple intravenous doses.

    Science.gov (United States)

    Zhao, Miao; Wu, Xiao-Jie; Fan, Ya-Xin; Zhang, Ying-Yuan; Guo, Bei-Ning; Yu, Ji-Cheng; Cao, Guo-Ying; Chen, Yuan-Cheng; Wu, Ju-Fang; Shi, Yao-Guo; Li, Jian; Zhang, Jing

    2018-05-01

    The high prevalence of extensively drug-resistant Gram-negative pathogens has forced clinicians to use colistin as a last-line therapy. Knowledge on the pharmacokinetics of colistin methanesulfonate (CMS), an inactive prodrug, and colistin has increased substantially; however, the pharmacokinetics in the Chinese population is still unknown due to lack of a CMS product in China. This study aimed to evaluate the pharmacokinetics of a new CMS product developed in China in order to optimise dosing regimens. A total of 24 healthy subjects (12 female, 12 male) were enrolled in single- and multiple-dose pharmacokinetic (PK) studies. Concentrations of CMS and formed colistin in plasma and urine were measured, and PK analysis was conducted using a non-compartmental approach. Following a single CMS dose [2.36 mg colistin base activity (CBA) per kg, 1 h infusion], peak concentrations (C max ) of CMS and formed colistin were 18.0 mg/L and 0.661 mg/L, respectively. The estimated half-life (t 1/2 ) of CMS and colistin were 1.38 h and 4.49 h, respectively. Approximately 62.5% of the CMS dose was excreted via urine within 24 h after dosing, whilst only 1.28% was present in the form of colistin. Following multiple CMS doses, colistin reached steady-state within 24 h; there was no accumulation of CMS, but colistin accumulated slightly (R AUC  = 1.33). This study provides the first PK data in the Chinese population and is essential for designing CMS dosing regimens for use in Chinese hospitals. The urinary PK data strongly support the use of intravenous CMS for serious urinary tract infections. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  18. Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy

    Directory of Open Access Journals (Sweden)

    F. A. Zeiler

    2015-01-01

    Full Text Available Background. Treatment of symptomatic delayed cerebral ischemia (DCI after subarachnoid hemorrhage (SAH is difficult. Recent studies suggest intravenous (IV high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm.

  19. Comparison of two doses of intravenous temsirolimus in patients with relapsed/refractory mantle cell lymphoma.

    Science.gov (United States)

    Jurczak, Wojciech; Ramanathan, Sundra; Giri, Pratyush; Romano, Alessandra; Mocikova, Heidi; Clancy, Jill; Lechuga, Mariajose; Casey, Michelle; Boni, Joseph; Giza, Agnieszka; Hess, Georg

    2018-03-01

    Temsirolimus 175 mg once-weekly for 3 weeks, followed by 75 mg once-weekly intravenously dosed (175/75 mg) is approved in the European Union for treatment of relapsed/refractory mantle cell lymphoma (MCL). A phase IV study explored whether similar efficacy, but improved safety could be achieved with 75 mg without 175 mg loading doses (ClinicaTrials.gov: NCT01180049). Patients with relapsed/refractory MCL were randomized to once-weekly temsirolimus 175/75 mg (n = 47) or 75 mg (n = 42). Treatment continued until objective disease progression. Primary endpoint: progression-free survival (PFS). Secondary endpoints included overall survival (OS) and adverse events (AEs). Median PFS was 4.3 versus 4.5 months (hazard ratio [HR] 0.731; 80% confidence interval [CI], 0.520-1.027), and median OS 18.7 versus 11.0 months (HR 0.681; 80% CI, 0.472-0.982) with 175/75 mg versus 75 mg. There were fewer patients with serious AEs, dose reduction, or death with 175/75 mg (57.4%, 48.9%, and 48.9%) versus 75 mg (73.8%, 64.3%, and 65.1%). Temsirolimus 175/75 mg remains the preferred dosing regimen for relapsed/refractory MCL.

  20. Pharmacokinetics of [14C]teicoplanin in male rats after single intravenous dose

    International Nuclear Information System (INIS)

    Bernareggi, A.; Cavenaghi, L.; Assandri, A.

    1986-01-01

    The pharmacokinetic profile of [ 14 C]teicoplanin was studied in male Sprague-Dawley rats given a single 10,000-U/kg intravenous dose. The disposition of the antimicrobial activity in the body was estimated by a three-compartment open model. Plasma concentration data were fitted to a three-exponent equation. The profile of total 14 C in plasma was similar to that of the microbiological activity. The cumulative recovery of total 14 C 5 days after drug administration averaged 76.3% of the administered dose in the urine and 8.7% in the feces. The residual dose remaining in the animal carcasses was 11.1%. Teicoplanin was widely distributed in the body. In almost all organs, the maximum concentration of [ 14 C]teicoplanin was already reached at the first time of killing, which was 0.25 h after the administration of drug. The liver, kidneys, skin, and fat contained most of the residual dose found in the animal carcasses 120 h after administration and behaved as a deep compartment with the adrenal glands and spleen

  1. [Single intravenous tranexamic acid dose to reduce blood loss in primary total knee replacement].

    Science.gov (United States)

    Sanz-Reig, J; Parra Ruiz, B; Ferrández Martínez, J; Martínez López, J F

    2016-01-01

    To evaluate the effectiveness and safety of a single intravenous dose of tranexamic acid in order to reduce blood loss in total knee replacement. Prospective observational study of the administration of tranexamic acid in patients undergoing primary total knee arthroplasty from November 2013 to February 2015, in which an autologous blood recovery system was used. The study included 98 patients, distributed into two groups of 49 patients according to whether or not they received intravenous tranexamic acid. The primary endpoint was the number of patients requiring autologous transfusion from the recovery system autologous blood recovery system. No drop-outs were recorded during follow-up. There were no significant differences between groups as regards the preoperative and hospital variables. The mean preoperative haemoglobin and haematocrit at 24 and 48 hours postoperatively were similar in both groups. The average volume of bleeding in the autologous blood recovery system and estimated average blood loss was lower in patients who had been administered tranexamic acid, with significant differences. No patients in the group that was administered tranexamic acid required blood autotransfusion. The transfusion rate was zero in the two groups. No adverse events related to the administration of tranexamic acid were recorded. Intravenous administration of tranexamic acid, according to the described protocol, has presented a non-autotransfusion or allo-transfusion rate of 100%, with no increased incidence of thrombotic events. Thus, its use in this group of patients is recommended. The indication should be individualized, its use justified in the patient medical records, and informed consent is mandatory. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

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

    NARCIS (Netherlands)

    Aten, J.J.; Oudega, M.L.; van Exel, E.; Stek, M.L.; van Waarde, J.A.

    2015-01-01

    In electroconvulsive therapy (ECT), a dose titration method (DTM) was suggested to be more individualized and therefore more accurate than formula-based dosing methods. A repeated DTM (every sixth session and dose adjustment accordingly) was compared to an age-based method (ABM) regarding treatment

  3. Review of high-dose intravenous vitamin C as an anticancer agent.

    Science.gov (United States)

    Wilson, Michelle K; Baguley, Bruce C; Wall, Clare; Jameson, Michael B; Findlay, Michael P

    2014-03-01

    In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well-designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high-dose oral vitamin C. Marked differences are now recognized in the pharmacokinetics of vitamin C with oral and IV administration, opening the issue of therapeutic efficacy to question. In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant but may have pro-oxidant activity at high concentrations. The mechanism of its pro-oxidant action is not fully understood, and both intra- and extracellular mechanisms that generate hydrogen peroxide have been proposed. It remains to be proven whether vitamin C-induced reactive oxygen species occur in vivo and, if so, whether this will translate to a clinical benefit. Current clinical evidence for a therapeutic effect of high-dose IV vitamin C is ambiguous, being based on case series. The interpretation and validation of these studies is hindered by limited correlation of plasma vitamin C concentrations with response. The methodology exists to determine if there is a role for high-dose IV vitamin C in the treatment of cancer, but the limited understanding of its pharmacodynamic properties makes this challenging. Currently, the use of high-dose IV vitamin C cannot be recommended outside of a clinical trial. © 2014 Wiley Publishing Asia Pty Ltd.

  4. Effect of high-dose intravenous vitamin C on inflammation in cancer patients

    Directory of Open Access Journals (Sweden)

    Mikirova Nina

    2012-09-01

    Full Text Available Abstract Background An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP are associated with poor prognosis and decreased survival in many types of cancer. Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels. Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. Methods 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g after standard treatments by conventional methods. CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. Results According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment. There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3 and changes in the levels of C-reactive protein. Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. Conclusions The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases

  5. Repeated exposure to intra-amniotic LPS partially protects against adverse effects of intravenous LPS in preterm lambs.

    Science.gov (United States)

    Gisslen, Tate; Hillman, Noah H; Musk, Gabrielle C; Kemp, Matthew W; Kramer, Boris W; Senthamaraikannan, Paranthaman; Newnham, John P; Jobe, Alan H; Kallapur, Suhas G

    2014-02-01

    Histologic chorioamnionitis, frequently associated with preterm births and adverse outcomes, results in prolonged exposure of preterm fetuses to infectious agents and pro-inflammatory mediators, such as LPS. Endotoxin tolerance-type effects were demonstrated in fetal sheep following repetitive systemic or intra-amniotic (i.a.) exposures to LPS, suggesting that i.a. LPS exposure would cause endotoxin tolerance to a postnatal systemic dose of LPS in preterm sheep. In this study, randomized pregnant ewes received either two i.a. injections of LPS or saline prior to preterm delivery. Following operative delivery, the lambs were treated with surfactant, ventilated, and randomized to receive either i.v. LPS or saline at 30  min of age. Physiologic variables and indicators of systemic and lung inflammation were measured. Intravenous LPS decreased blood neutrophils and platelets values following i.a. saline compared to that after i.a. LPS. Intra-amniotic LPS prevented blood pressure from decreasing following the i.v. LPS, but also caused an increased oxygen index. Intra-amniotic LPS did not cause endotoxin tolerance as assessed by cytokine expression in the liver, lung or plasma, but increased myeloperoxidase-positive cells in the lung. The different compartments of exposure to LPS (i.a. vs i.v.) are unique to the fetal to newborn transition. Intra-amniotic LPS incompletely tolerized fetal lambs to postnatal i.v. LPS.

  6. Phase I dose escalation pharmacokinetic assessment of intravenous humanized anti-MUC1 antibody AS1402 in patients with advanced breast cancer.

    Science.gov (United States)

    Pegram, Mark D; Borges, Virginia F; Ibrahim, Nuhad; Fuloria, Jyotsna; Shapiro, Charles; Perez, Susan; Wang, Karen; Schaedli Stark, Franziska; Courtenay Luck, Nigel

    2009-01-01

    MUC1 is a cell-surface glycoprotein that establishes a molecular barrier at the epithelial surface and engages in morphogenetic signal transduction. Alterations in MUC1 glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion, and immune surveillance. A 20-amino-acid tandem repeat that forms the core protein of MUC1 is overexpressed and aberrantly glycosylated in the majority of epithelial tumors. AS1402 (formerly R1550) is a humanized IgG1k monoclonal antibody that binds to PDTR sequences within this tandem repeat that are not exposed in normal cells. AS1402 is a potent inducer of antibody-dependent cellular cytotoxicity (ADCC), specifically against MUC1-expressing tumor cells. The objective of this study was to determine the safety, tolerability, and pharmacokinetic (PK) characteristics of AS1402 monotherapy in patients with locally advanced or metastatic MUC1-positive breast cancer that had progressed after anthracyclines- and taxane-based therapy. Patients received AS1402 over a 1- to 3-hour intravenous (i.v.) infusion at doses between 1 and 16 mg/kg, with repeated dosing every 1 to 3 weeks (based on patient-individualized PK assessment) until disease progression. Serum AS1402 levels were measured at multiple times after i.v. administration. Human anti-human antibody (HAHA) responses were measured to determine the immunogenicity of AS1402. Noncompartmental pharmacokinetic parameters were determined and were used to assess dose dependency across the dose range studied. Twenty-six patients were treated. AS1402 was generally well tolerated. Two grade 3/4 drug-related adverse events were reported, both at the 3-mg/kg dose. Neither was observed in expanded or subsequent dosing cohorts. No anti-human antibodies were detected. Plasma concentrations of AS1402 appeared to be proportional to dose within the 1- to 16-mg/kg dose range assessed, with a mean terminal half-life of 115.4 +/- 37.1 hours

  7. [Conscious sedation and amnesic effect of intravenous low-dose midazolam prior to spinal anesthesia].

    Science.gov (United States)

    Koyama, Shinichi; Ohashi, Naotsugu; Kurita, Satoshi; Nakatani, Keiji; Nagata, Noboru; Toyoda, Yoshiroh

    2008-06-01

    The pain associated with spinal puncture is severe, and the memory of this uncomfortable procedure often deters patients from undergoing the procedure again. Therefore, it is important to make the patient as comfortable as possible when this procedure is performed. We administrated a low-dose (1-2.5 mg) of midazolam intravenously several minutes before conducting a spinal-tap in 200 patients undergoing elective surgery of the lower limb. The dose of midazolam used was based on the patient's age and weight, and we investigated remaining of a memory concerning the spinal-tap procedure and side effects of midazolam at the end of surgery. Memory of the spinal-tap procedure remained in 14.0%, 1.9%, and 32.7% of the patients who had received benzodiazepine preoperatively and in 25.0%, 40.0%, and 60.9% of the patients who hadn't received benzodiazepine preoperatively in the age group or =70 years, respectively. No patient experienced severe respiratory depression, but an excessive sedation or restlessness was experienced in 1.6%, 4.8%, and 5.2% of the patients. In the patients aged memory concerning the spinal-tap procedure; however, it is important to note that the number of side effects associated with this procedure increases in patients aged > or =60 years.

  8. The importance of active learning and practice on the students' mastery of pharmacokinetic calculations for the intermittent intravenous infusion dosing of antibiotics

    Directory of Open Access Journals (Sweden)

    Mehvar Reza

    2012-11-01

    Full Text Available Abstract Background Estimation of pharmacokinetic parameters after intermittent intravenous infusion (III of antibiotics, such as aminoglycosides or vancomycin, has traditionally been a difficult subject for students in clinical pharmacology or pharmacokinetic courses. Additionally, samples taken at different intervals during repeated dose therapy require manipulation of sampling times before accurate calculation of the patient-specific pharmacokinetic parameters. The main goal of this study was to evaluate the effectiveness of active learning tools and practice opportunities on the ability of students to estimate pharmacokinetic parameters from the plasma samples obtained at different intervals following intermittent intravenous infusion. Methods An extensive reading note, with examples, and a problem case, based on a patient’s chart data, were created and made available to students before the class session. Students were required to work through the case before attending the class. The class session was devoted to the discussion of the case requiring active participation of the students using a random participation program. After the class, students were given additional opportunities to practice the calculations, using online modules developed by the instructor, before submitting an online assignment. Results The performance of students significantly (P P  Conclusions Despite being a difficult subject, students achieve mastery of pharmacokinetic calculations for the topic of intermittent intravenous infusion when appropriate active learning strategies and practice opportunities are employed.

  9. Distribution of 14C-lindane in the rat after a single dose intraperitoneal and intravenous injection

    International Nuclear Information System (INIS)

    Lievremont, Maurice; Le Flohic, J.-F.; Pascaud, Marc

    1981-01-01

    14 C-Lindane retentions in rat tissues were studied until 24 hrs after a single dose pesticide administration. Each organ shows particular kinetics. Adipose tissue is the most active in pesticide fixation but the lungs retain momentarily a large fraction of Lindane after intravenous injection [fr

  10. Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

    Directory of Open Access Journals (Sweden)

    Rui-Rui Peng

    2017-03-01

    Full Text Available Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai.Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13% and 0.35% (95% CI: 0.06-1.39%, respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients, fatigue (2 patients, cough (1 patient, sore throat (1 patient, diarrhea (1 patient and erythematous rash (1 patient. The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05. Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia.Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for

  11. Radiation dose exposure in patients affected by lymphoma undergoing repeat CT examinations: how to manage the radiation dose variability.

    Science.gov (United States)

    Paolicchi, Fabio; Bastiani, Luca; Guido, Davide; Dore, Antonio; Aringhieri, Giacomo; Caramella, Davide

    2018-03-01

    To assess the variability of radiation dose exposure in patients affected by lymphoma undergoing repeat CT (computed tomography) examinations and to evaluate the influence of different scan parameters on the overall radiation dose. A series of 34 patients (12 men and 22 women with a median age of 34.4 years) with lymphoma, after the initial staging CT underwent repeat follow-up CT examinations. For each patient and each repeat examination, age, sex, use of AEC system (Automated Exposure Control, i.e. current modulation), scan length, kV value, number of acquired scans (i.e. number of phases), abdominal size diameter and dose length product (DLP) were recorded. The radiation dose of just one venous phase was singled out from the DLP of the entire examination. All scan data were retrieved by our PACS (Picture Archiving and Communication System) by means of a dose monitoring software. Among the variables we considered, no significant difference of radiation dose was observed among patients of different ages nor concerning tube voltage. On the contrary the dose delivered to the patients varied depending on sex, scan length and usage of AEC. No significant difference was observed depending on the behaviour of technologists, while radiologists' choices had indirectly an impact on the radiation dose due to the different number of scans requested by each of them. Our results demonstrate that patients affected by lymphoma who undergo repeat whole body CT scanning may receive unnecessary overexposure. We quantified and analyzed the most relevant variables in order to provide a useful tool to manage properly CT dose variability, estimating the amount of additional radiation dose for every single significant variable. Additional scans, incorrect scan length and incorrect usage of AEC system are the most relevant cause of patient radiation exposure.

  12. Pharmacokinetics of lansoprazole and its main metabolites after single intravenous doses in healthy Chinese subjects.

    Science.gov (United States)

    Zhang, Dan; Yang, Man; Liu, Man; Zhang, Yanan; Wang, Xiaolin; Xiao, Xue; Liu, Huichen

    2012-11-01

    The aim of the study was to evaluate the pharmacokinetics (PK) of lansoprazole (LPZ) and its main metabolites 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulphone (LPZS) after single intravenous (i.v.) doses of LPZ in healthy Chinese subjects, and the relationship between the cytochrome P450 (CYP) 2C19 phenotypes and the plasma concentrations of LPZS at the time-points in the elimination phase of LPZ. Twelve subjects were given lansoprazole by i.v. infusion. Blood samples were collected at designated time points up to 24 h. Plasma concentrations of LPZ, HLPZ and LPZS were quantified by a selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. After single i.v. doses of 15, 30 and 60 mg LPZ, C(max) and area under the plasma concentration-time curve (AUC(0-t)) of LPZ were 725 ± 151, 1480 ± 190, 3130 ± 480 µg · L(-1) and 1690 ± 1210, 3630 ± 2530, 8080 ± 4550 µg · h · L(-1), respectively. LPZ was generally well tolerated in healthy Chinese subjects, and displayed linear PK in the range of 15-60 mg. There were significant differences in the elimination of LPZ and the formation of LPZS between the single CYP2C19 poor metabolizer (PM) and the CYP2C19 extensive metabolizers (EM). The concentration of LPZS at the time-points in the elimination phase of LPZ could be monitored for CYP2C19 phenotyping. As a probe drug for CYP2C19 phenotyping, LPZ for injection might be more suitable than LPZ oral formulations.

  13. Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis.

    Science.gov (United States)

    Moretti, Michele; Buiatti, Alessandra; Merlo, Marco; Massa, Laura; Fabris, Enrico; Pinamonti, Bruno; Sinagra, Gianfranco

    2013-11-01

    The management of refractory recurrent pericarditis is challenging. Previous clinical reports have noted a beneficial effect of high-dose intravenous human immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related forms. In this article, we analyzed retrospectively our clinical experience with IvIg therapy in a series of clinical cases of pericarditis refractory to conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010) with refractory recurrent pericarditis, who received high-dose IvIg as a part of their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine treatment was not discontinued during IvIg treatment. No patients had a history of autoimmune or connective tissue diseases. During an average period of 11 months from the first recurrence, patients had experienced a mean of 5 relapses before the first IvIg treatment. In 4 cases, patients showed complete clinical remission with no further relapse after the first IvIg cycle. Two patients experienced a single minor relapse, responsive to short-term nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle of IvIg after a recurrence of pericarditis, with subsequent complete remission. One patient did not respond to 3 cycles of IvIg and subsequently underwent pericardial window and long-term immunosuppressive treatment. No major adverse effect was observed in consequence of IvIg administration in all the cases. In conclusion, although IvIg mode of action is still poorly understood in this setting, this treatment can be considered as an option in patients with recurrent pericarditis refractory to conventional medical treatment and, in our small series, has proved to be effective in 8 of 9 cases. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Influence of intravenous contrast agent on dose calculations of intensity modulated radiation therapy plans for head and neck cancer

    International Nuclear Information System (INIS)

    Choi, Youngmin; Kim, Jeung-Kee; Lee, Hyung-Sik; Hur, Won-Joo; Hong, Young-Seoub; Park, Sungkwang; Ahn, Kijung; Cho, Heunglae

    2006-01-01

    Background and purpose: To evaluate the effect of an intravenous contrast agent (CA) on dose calculations and its clinical significance in intensity modulated radiation therapy (IMRT) plans for head and neck cancer. Materials and methods: Fifteen patients with head and neck cancer and involved neck nodes were enrolled. Each patient took two sets of computerized tomography (CT) in the same position before and after intravenous CA injections. Target volumes and organs at risk (OAR) were contoured on the enhanced CT, and then an IMRT plan of nine equiangular beams with a 6 MV X-ray was created. After the fusion of non-enhanced and enhanced CTs, the contours and the IMRT plan created from the enhanced CT were copied and placed to the non-enhanced CT. Doses were calculated again from the non-enhanced CT by the same IMRT plan. The radiation doses calculated from the two sets of CTs were compared with regard to planning target volumes (PTV) and the three OARs, both parotid glands and the spinal cord, by Wilcoxon's signed rank test. Results: The doses (maximum, mean, and the dose of 95% of PTV received (D 95% )) of PTV70 and PTV59.4 calculated from the enhanced CTs were lower than those from the non-enhanced CTs (p < 0.05), but the dose differences were less than 1% compared to the doses calculated from the enhanced CTs. The doses of PTV50.4, parotid glands, and spinal cord were not significantly different between the non-enhanced and enhanced CTs. Conclusions: The difference between the doses calculated from the CTs with and without CA enhancement was tolerably small, therefore using intravenous CA could be recommended for the planning CT of head and neck IMRT

  15. Comparative evaluation of prophylactic single-dose intravenous antibiotic with postoperative antibiotics in elective urologic surgery

    Directory of Open Access Journals (Sweden)

    Mohammad K Moslemi

    2010-11-01

    site infection rates of categories A and B in Group 1 were 0 and two (0.86%, respectively, while those in Group 2 were 0 and five (0.92%, respectively. There was no significant difference in infection rates in terms of remote infection and surgical site infection between Group 1 and Group 2 (P = 0.670. The amounts, as well as the prices, for intravenously administered antibiotics decreased to approximately one quarter.Conclusion: Our protocol effectively decreased the amount of antibiotics used without increasing perioperative infection rates. Thus, our protocol of prophylactic antibiotic therapy can be recommended as an appropriate method for preventing perioperative infection in urologic surgery. Keywords: surgical site infection, antibiotic prophylaxis, single dose, urologic surgery

  16. Low-dose intravenous alpha-2 agonists as adjuvants to spinal levobupivacaine: A randomized study

    Directory of Open Access Journals (Sweden)

    Pranav Jetley

    2017-01-01

    Full Text Available Background: Alpha-2 agonists have been used with spinal anesthesia for anxiolysis, analgesia, and hypnosis and for postoperative pain relief. These beneficial effects may, however, be offset by their propensity to prolong the duration of motor block and adversely affect hemodynamics when used in higher doses. This study compares the effects of low-dose premedication with intravenous (IV dexmedetomidine and IV clonidine with placebo, on spinal blockade duration, analgesia, and sedation with intrathecal levobupivacaine. Materials and Methods: In this prospective, randomized, double-blinded, placebo-controlled study, ninety American Society of Anesthesiologists Status I and II patients were randomly allocated into three groups: Group A (control received 10 ml normal saline IV, Group B received IV dexmedetomidine 0.6 μg/kg, and Group C received IV clonidine 1.2 μg/kg over 10 min, before spinal anesthesia with 0.5% levobupivacaine. Hemodynamics, total duration of analgesia, onset and duration of sensory and motor block, visual analog scale score, and sedation score were assessed. Complications, if any, were noted. Results: The level of sensory block achieved was higher with dexmedetomidine (T4.2 ± 0.8 and clonidine (T4.4 ± 0.7 as compared to control (T5.1 ± 0.7; P< 0.001. Time to two segment regression was greater with dexmedetomidine (146.5 ± 12.5 min and clonidine (138.9 ± 17.4 min compared to control (90.1 ± 9.4; P< 0.001. Dexmedetomidine maximally prolonged the duration to first patient request for analgesia (245.2 ± 26.8 min, followed by clonidine (175.3 ± 20.1 min, P< 0.001 and control (121.3 ± 16.1 min, P< 0.001. The duration of motor block was similar in all three groups. Incidence of bradycardia was significantly greater with both dexmedetomidine and clonidine compared to saline (P < 0.05. Conclusion: Premedication with low-dose IV dexmedetomidine and clonidine prolonged sensory blockade and analgesic duration and provided

  17. The route of administration (oral vs intravenous) does not influence dose or outcome in Graves' disease and unifocal autonomy

    International Nuclear Information System (INIS)

    Schneider, Peter; Biko, Johannes; Haenscheid, Heribert; Hilliger, Stephan; Koutsampelas, Christos; Kranzfelder, Michael; Ladner, Stephan; Reiners, Christoph

    2005-01-01

    In a prospective randomised study, we investigated the influence of the route of administration of radioiodide on dosimetry and therapy outcome. Fifty-four patients suffering from Graves' disease (GD) and 60 patients with unifocal autonomy (UA) participated in the study and were randomly treated with either orally or intravenously administered radioiodide. Pretherapeutic dosimetry was based on single uptake measurements with a calibrated uptake probe system. The radioiodine kinetics during hospitalisation was assessed by daily bedside uptake measurements. Therapeutic dose was determined by half-life and thyroid uptake at the time of discharge using the same uptake probe as for the radioiodine test. No improvement in accuracy of dosimetry was achieved when radioiodide was administered intravenously. Mean therapeutic doses were identical following intravenous or oral administration. Variation in the achieved dose was slightly higher in the patients receiving oral administration, this being attributable to larger deviations in discrete activities of the capsules administered as compared with the values determined by dosimetry. No differences according to treatment modality were found with regard to therapeutic outcome. Eighty-seven patients attended 6-month follow-up after therapy. In the UA group, successful treatment, defined as a normal or elevated TSH level, was observed in 94% of patients after oral administration and in 80% after intravenous administration; corresponding figures in the GD group were 68% and 65%. The causes of individual differences between targeted and therapeutically achieved doses remain undetermined. Variations in the bioavailability of radioiodide or other parameters affecting thyroid status may be involved, and further investigations are needed to clarify this. (orig.)

  18. Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

    Science.gov (United States)

    Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

    2014-01-01

    Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

  19. Impact of intravenous contrast used in computed tomography on radiation dose to carotid arteries and thyroid in intensity-modulated radiation therapy planning for nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Victor Ho Fun, E-mail: vhflee@hku.hk; Ng, Sherry Chor Yi; Kwong, Dora Lai Wan; Lam, Ka On; Leung, To Wai

    2017-07-01

    The aim of this study was to investigate if intravenous contrast injection affected the radiation doses to carotid arteries and thyroid during intensity-modulated radiation therapy (IMRT) planning for nasopharyngeal carcinoma (NPC). Thirty consecutive patients with NPC underwent plain computed tomography (CT) followed by repeated scanning after contrast injection. Carotid arteries (common, external, internal), thyroid, target volumes, and other organs-at-risk (OARs), as well as IMRT planning, were based on contrast-enhanced CT (CE-CT) images. All these structures and the IMRT plans were then copied and transferred to the non–contrast-enhanced CT (NCE-CT) images, and dose calculation without optimization was performed again. The radiation doses to the carotid arteries and the thyroid based on CE-CT and NCE-CT were then compared. Based on CE-CT, no statistical differences, despite minute numeric decreases, were noted in all dosimetric parameters (minimum, maximum, mean, median, D05, and D01) of the target volumes, the OARs, the carotid arteries, and the thyroid compared with NCE-CT. Our results suggested that compared with NCE-CT planning, CE-CT scanning should be performed during IMRT for better target and OAR delineation, without discernible change in radiation doses.

  20. Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4 h apart Human pharmacology of MDMA after repeated doses taken 4 h apart.

    Science.gov (United States)

    Farré, Magí; Tomillero, Angels; Pérez-Mañá, Clara; Yubero, Samanta; Papaseit, Esther; Roset, Pere-Nolasc; Pujadas, Mitona; Torrens, Marta; Camí, Jordi; de la Torre, Rafael

    2015-10-01

    3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  1. Clonidine as an adjunct to intravenous regional anesthesia: A randomized, double-blind, placebo-controlled dose ranging study

    Directory of Open Access Journals (Sweden)

    Clarence S Ivie

    2011-01-01

    Full Text Available Background : The addition of clonidine to lidocaine intravenous regional anesthesia (IVRA has been previously reported to improve postoperative analgesia in patients undergoing upper extremity surgery. Our objective was to perform a dose ranging study in order to determine the optimal dose of clonidine used with lidocaine in IVRA. Design & Setting : We performed a double-blinded randomized placebo-controlled study with 60 patients scheduled for elective endoscopic carpal tunnel release under IVRA with 50 ml lidocaine 0.5%. University-affiliated outpatient surgery center. Data collected in operating rooms, recovery room, and by telephone after discharge from surgery center. Materials & Methods : Sixty adult ASA I or II patients undergoing outpatient endoscopic carpal tunnel release under intravenous regional anesthesia.Patients were randomized into five study groups receiving different doses of clonidine in addition to 50 ml 0.5% lidocaine in their IVRA. Group A received 0 mcg/kg, group B 0.25 mcg/kg, group C 0.5 mcg/kg, group D 1.0 mcg/kg and group E 1.5 mcg/kg of clonidine.Intraoperative fentanyl, recovery room pain scores, time to first postsurgical analgesic, total number of acetaminophen/codeine tablets consumed postsurgery, incidence of sedation, hypotension and bradycardia. Results & Conclusions : There was no benefit from any dose of clonidine compared to placebo. There were no clonidine-related side effects seen within the dose range studied. In short duration minor hand surgery, the addition of clonidine to lidocaine-based intravenous regional anesthesia provides no measurable benefit.

  2. A GPU implementation of a track-repeating algorithm for proton radiotherapy dose calculations

    International Nuclear Information System (INIS)

    Yepes, Pablo P; Mirkovic, Dragan; Taddei, Phillip J

    2010-01-01

    An essential component in proton radiotherapy is the algorithm to calculate the radiation dose to be delivered to the patient. The most common dose algorithms are fast but they are approximate analytical approaches. However their level of accuracy is not always satisfactory, especially for heterogeneous anatomical areas, like the thorax. Monte Carlo techniques provide superior accuracy; however, they often require large computation resources, which render them impractical for routine clinical use. Track-repeating algorithms, for example the fast dose calculator, have shown promise for achieving the accuracy of Monte Carlo simulations for proton radiotherapy dose calculations in a fraction of the computation time. We report on the implementation of the fast dose calculator for proton radiotherapy on a card equipped with graphics processor units (GPUs) rather than on a central processing unit architecture. This implementation reproduces the full Monte Carlo and CPU-based track-repeating dose calculations within 2%, while achieving a statistical uncertainty of 2% in less than 1 min utilizing one single GPU card, which should allow real-time accurate dose calculations.

  3. Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges.

    Directory of Open Access Journals (Sweden)

    Roland R Regoes

    2005-08-01

    Full Text Available Trials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against "real life" exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses.Using statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success.Preclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.

  4. Repeated CT scans in trauma transfers: An analysis of indications, radiation dose exposure, and costs

    International Nuclear Information System (INIS)

    Hinzpeter, Ricarda; Sprengel, Kai; Wanner, Guido A.; Mildenberger, Peter; Alkadhi, Hatem

    2017-01-01

    Highlights: • Repetition of CT in trauma patients occurs relatively often. • Repetition of CT is mainly caused by inadequate image data transfer. • Potentially preventable CT examinations add radiation dose to patients. • Repeated CT is associated with excess costs to the health care system. - Abstract: Objectives: To identify the number of CT scans repeated in acute trauma patients receiving imaging before being referred to a trauma center, to define indications, and to assess radiation doses and costs of repeated CT. Methods: This retrospective study included all adult trauma patients transferred from other hospitals to a Level-I trauma center during 2014. Indications for repeated CT scans were categorized into: inadequate CT image data transfer, poor image quality, repetition of head CT after head injury together with completion to whole-body CT (WBCT), and follow-up of injury known from previous CT. Radiation doses from repeated CT were determined; costs were calculated using a nation-wide fee schedule. Results: Within one year, 85/298 (28.5%) trauma patients were transferred from another hospital because of severe head injury (n = 45,53%) and major body trauma (n = 23;27%) not manageable in the referring hospital, repatriation from a foreign country (n = 14;16.5%), and no ICU-capacity (n = 3;3.5%). Of these 85 patients, 74 (87%) had repeated CT in our center because of inadequate CT data transfer (n = 29;39%), repetition of head CT with completion to WBCT (n = 24;32.5%), and follow-up of known injury (n = 21;28.5%). None occurred because of poor image quality. Cumulative dose length product (DLP) and annual costs of potential preventable, repeated CT (inadequate data transfer) was 631mSv (81′304mGy*cm) and 35′233€, respectively. Conclusion: A considerable number of transferred trauma patients undergo potentially preventable, repeated CT, adding radiation dose to patients and costs to the health care system.

  5. Repeated CT scans in trauma transfers: An analysis of indications, radiation dose exposure, and costs

    Energy Technology Data Exchange (ETDEWEB)

    Hinzpeter, Ricarda, E-mail: Ricarda.Hinzpeter@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Raemistr. 100, Zurich CH-8091 (Switzerland); Sprengel, Kai, E-mail: Kai.Sprengel@usz.ch [Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Raemistr. 100, CH-8091 Zurich (Switzerland); Wanner, Guido A., E-mail: Guido.Wanner@sbk-vs.de [Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Raemistr. 100, CH-8091 Zurich (Switzerland); Department of General Surgery, Schwarzwald-Baar Klinikum, University of Freiburg, Klinikstr. 11, D-78052 Villingen-Schwenningen (Germany); Mildenberger, Peter, E-mail: peter.mildenberger@unimedizin-mainz.de [Department of Diagnostic and Interventional Radiology, University Hospital of Mainz, Langenbeckstr. 1, D-55131 Mainz (Germany); Alkadhi, Hatem, E-mail: hatem.alkadhi@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Raemistr. 100, Zurich CH-8091 (Switzerland)

    2017-03-15

    Highlights: • Repetition of CT in trauma patients occurs relatively often. • Repetition of CT is mainly caused by inadequate image data transfer. • Potentially preventable CT examinations add radiation dose to patients. • Repeated CT is associated with excess costs to the health care system. - Abstract: Objectives: To identify the number of CT scans repeated in acute trauma patients receiving imaging before being referred to a trauma center, to define indications, and to assess radiation doses and costs of repeated CT. Methods: This retrospective study included all adult trauma patients transferred from other hospitals to a Level-I trauma center during 2014. Indications for repeated CT scans were categorized into: inadequate CT image data transfer, poor image quality, repetition of head CT after head injury together with completion to whole-body CT (WBCT), and follow-up of injury known from previous CT. Radiation doses from repeated CT were determined; costs were calculated using a nation-wide fee schedule. Results: Within one year, 85/298 (28.5%) trauma patients were transferred from another hospital because of severe head injury (n = 45,53%) and major body trauma (n = 23;27%) not manageable in the referring hospital, repatriation from a foreign country (n = 14;16.5%), and no ICU-capacity (n = 3;3.5%). Of these 85 patients, 74 (87%) had repeated CT in our center because of inadequate CT data transfer (n = 29;39%), repetition of head CT with completion to WBCT (n = 24;32.5%), and follow-up of known injury (n = 21;28.5%). None occurred because of poor image quality. Cumulative dose length product (DLP) and annual costs of potential preventable, repeated CT (inadequate data transfer) was 631mSv (81′304mGy*cm) and 35′233€, respectively. Conclusion: A considerable number of transferred trauma patients undergo potentially preventable, repeated CT, adding radiation dose to patients and costs to the health care system.

  6. Repeated intravenous administration of gadobutrol does not lead to increased signal intensity on unenhanced T1-weighted images - a voxel-based whole brain analysis

    Energy Technology Data Exchange (ETDEWEB)

    Langner, Soenke; Kromrey, Marie-Luise [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Kuehn, Jens-Peter [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); University Hospital, Carl Gustav Carus University Dresden, Institute for Radiology, Dresden (Germany); Grothe, Matthias [University Medicine Greifswald, Department of Neurology, Greifswald (Germany); Domin, Martin [University Medicine Greifswald, Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany)

    2017-09-15

    To identify a possible association between repeated intravenous administration of gadobutrol and increased signal intensity in the grey and white matter using voxel-based whole-brain analysis. In this retrospective single-centre study, 217 patients with a clinically isolated syndrome underwent baseline brain magnetic resonance imaging and at least one annual follow-up examination with intravenous administration of 0.1 mmol/kg body weight of gadobutrol. Using the ''Diffeomorphic Anatomical Registration using Exponentiated Lie algebra'' (DARTEL) normalisation process, tissue templates for grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were calculated, as were GM-CSF and WM-CSF ratios. Voxel-based whole-brain analysis was used to calculate the signal intensity for each voxel in each data set. Paired t-test was applied to test differences to baseline MRI for significance. Voxel-based whole-brain analysis demonstrated no significant changes in signal intensity of grey and white matter after up to five gadobutrol administrations. There was no significant change in GM-CSF and grey WM-CSF ratios. Voxel-based whole-brain analysis did not demonstrate increased signal intensity of GM and WM on unenhanced T1-weighted images after repeated gadobutrol administration. The molecular structure of gadolinium-based contrast agent preparations may be an essential factor causing SI increase on unenhanced T1-weighted images. (orig.)

  7. Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies

    International Nuclear Information System (INIS)

    Mejia, A.A.; Nakamura, T.; Masatoshi, I.; Hatazawa, J.; Masaki, M.; Watanuki, S.

    1991-01-01

    Radiation absorbed doses due to intravenous administration of fluorine-18-fluorodeoxyglucose in positron emission tomography (PET) studies were estimated in normal volunteers. The time-activity curves were obtained for seven human organs (brain, heart, kidney, liver, lung, pancreas, and spleen) by using dynamic PET scans and for bladder content by using a single detector. These time-activity curves were used for the calculation of the cumulative activity in these organs. Absorbed doses were calculated by the MIRD method using the absorbed dose per unit of cumulated activity, 'S' value, transformed for the Japanese physique and the organ masses of the Japanese reference man. The bladder wall and the heart were the organs receiving higher doses of 1.2 x 10(-1) and 4.5 x 10(-2) mGy/MBq, respectively. The brain received a dose of 2.9 x 10(-2) mGy/MBq, and other organs received doses between 1.0 x 10(-2) and 3.0 x 10(-2) mGy/MBq. The effective dose equivalent was estimated to be 2.4 x 10(-2) mSv/MBq. These results were comparable to values of absorbed doses reported by other authors on the radiation dosimetry of this radiopharmaceutical

  8. High dose intravenous iron, mineral homeostasis and intact FGF23 in normal and uremic rats

    DEFF Research Database (Denmark)

    Gravesen, Eva; Hofman-Bang, Jacob; Mace, Maria L.

    2013-01-01

    High iron load might have a number of toxic effects in the organism. Recently intravenous (iv) iron has been proposed to induce elevation of fibroblast growth factor 23 (FGF23), hypophosphatemia and osteomalacia in iron deficient subjects. High levels of FGF23 are associated with increased...

  9. Safety and Pharmacokinetic Profiles of Repeated-Dose Micafungin in Children and Adolescents Treated for Invasive Candidiasis

    Science.gov (United States)

    Benjamin, Daniel K.; Deville, Jaime G.; Azie, Nkechi; Kovanda, Laura; Roy, Mike; Wu, Chunzhang; Arrieta, Antonio

    2013-01-01

    Background Micafungin is an echinocandin with proven efficacy against a broad range of fungal infections, including those caused by Candida species. Objective To evaluate the safety and pharmacokinetics of once-daily 3 mg/kg and 4.5 mg/kg micafungin in children with proven, probable, or suspected invasive candidiasis. Methods Micafungin safety and pharmacokinetics were assessed in two Phase I, open-label, repeat-dose trials. In Study 2101, children aged 2–16 years were grouped by weight to receive 3 mg/kg (≥25 kg) or 4.5 mg/kg (<25 kg) intravenous micafungin for 10–14 days. In Study 2102, children aged 4 months to <2 years received 4.5 mg/kg micafungin. Study protocols were otherwise identical. Results Safety was analyzed in seventy-eight and nine children in Studies 2101 and 2102, respectively. Although adverse events were experienced by most children (2101: n = 62; 2102: n = 9), micafungin-related adverse events were less common (2101: n = 28; 2102: n = 1), and the number of patients discontinuing due to adverse events was low (2101: n = 4; 2102: n = 1). The most common micafungin-related adverse events were infusion-associated symptoms, pyrexia, and hypomagnesemia (Study 2101), and liver function abnormalities (Study 2102). The micafungin pharmacokinetic profile was similar to that seen in other studies conducted in children, but different than that observed in adults. Conclusions In this small cohort of children, once-daily doses of 3 mg/kg and 4.5 mg/kg micafungin were well tolerated. Pharmacokinetic data will be combined in a population pharmacokinetic analysis to support U.S. dosing recommendations in children. PMID:23958810

  10. Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

    Science.gov (United States)

    Sesé, L; Gaouar, H; Autegarden, J-E; Alari, A; Amsler, E; Vial-Dupuy, A; Pecquet, C; Francès, C; Soria, A

    2016-03-01

    The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%). © 2016 John Wiley & Sons Ltd.

  11. Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

    Science.gov (United States)

    Tanaka, Emi; Ogawa, Yuko; Mukai, Takeo; Sato, Yoshiaki; Hamazaki, Takashi; Nagamura-Inoue, Tokiko; Harada-Shiba, Mariko; Shintaku, Haruo; Tsuji, Masahiro

    2018-01-01

    Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs) have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12), and low-dose (1 × 104) or high-dose (1 × 105) UC-MSCs were administered intravenously 48 h after the insult (P14). To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by modulating

  12. Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

    Directory of Open Access Journals (Sweden)

    Emi Tanaka

    2018-03-01

    Full Text Available Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12, and low-dose (1 × 104 or high-dose (1 × 105 UC-MSCs were administered intravenously 48 h after the insult (P14. To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by

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

    Science.gov (United States)

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

    2015-06-01

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

  14. The changes in renal function after a single dose of intravenous furosemide in patients with compensated liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Mejirisky Yoram

    2006-11-01

    Full Text Available Abstract Background Patients with compensated Child-A cirrhosis have sub clinical hypovolemia and diuretic treatment could result in renal impairment. Aim To evaluate the changes in renal functional mass as reflected by DMSA uptake after single injection of intravenous furosemide in patients with compensated liver cirrhosis. Methods Eighteen cirrhotic patients were divided in two groups; eight patients (group 1, age 56 ± 9.6 yrs, Gender 5M/3F, 3 alcoholic and 5 non alcoholic were given low intravenous 40 mg furosemide and ten other patients (group 2, age 54 ± 9.9, Gender 6M/4F, 4 alcoholic and 6 non alcoholic were given high 120 mg furosemide respectively. Renoscintigraphy with 100MBq Of Tc 99 DMSA was given intravenously before and 90 minutes after furosemide administration and SPECT imaging was determined 3 hours later. All patients were kept under low sodium diet (80mEq/d and all diuretics were withdrawn for 3 days. 8-hours UNa exertion, Calculated and measured Creatinine clearance (CCT were performed for all patients. Results Intravenous furosemide increased the mean renal DMSA uptake in 55% of patients with compensated cirrhosis and these changes persist up to three hours after injection. This increase was at the same extent in either low or high doses of furosemide. (From 12.8% ± 3.8 to 15.2% ± 2.2, p 40%, as compared to normal calculated creatinine clearance (CCT 101 ± 26, and measured CCT of 87 ± 30 cc/min (P Conclusion A single furosemide injection increases renal functional mass as reflected by DMSA in 55% of patients with compensated cirrhosis and identify 45% of patients with reduced uptake and who could develop renal impairment under diuretics. Whether or not albumin infusion exerts beneficial effect in those patients with reduced DMSA uptake remains to be determined.

  15. Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2g starting dose following third molar surgery

    DEFF Research Database (Denmark)

    Juhl, Gitte Irene; Nørholt, Sven E.; Tønnesen, Else Kirstine

    2006-01-01

    BACKGROUND: The recommended dose for intravenous (IV) paracetamol injection in adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2g starting dose. METHODS: A single-centre, randomised, double-blind, placebo-controlled, 3......-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2g, IV paracetamol 1g or placebo. Efficacy and safety were evaluated...... over 8h. Laboratory tests were performed before and 48h after drug administration. RESULTS: Two hundred and ninety seven patients (132=IV paracetamol 2g; 132=IV paracetamol 1g; 33=placebo) were randomised and completed the study. The summed pain relief over 6h (TOTPAR6) was significantly superior...

  16. Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate.

    Science.gov (United States)

    Jia, Minghong; Coats, Bonnie; Chadha, Monisha; Frentzen, Barbara; Perez-Rodriguez, Javier; Chadik, Paul A; Yost, Richard A; Henderson, George N; Stacpoole, Peter W

    2006-12-01

    Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity. We sought to determine the kinetics of environmentally relevant concentrations of 1,2-(13)C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 microg/kg of 1,2-(13)C-DCA. Plasma and urine concentrations of 1,2-(13)C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-(13)C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-(13)C-DCA peaked 10 minutes and 30 minutes after intravenous or oral administration, respectively. Plasma kinetic parameters varied as a function of dose and duration. Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health.

  17. Effect of Intravenous High Dose Vitamin C on Postoperative Pain and Morphine Use after Laparoscopic Colectomy: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Younghoon Jeon

    2016-01-01

    Full Text Available Background and Objective. Vitamin C has antioxidant, neuroprotective, and neuromodulating effects. Recently, it showed antinociceptive effect as a result of the antioxidant properties. Therefore, we designed this study to assess the effect of intravenous vitamin C on opiate consumption and pain in patients undergoing laparoscopic colectomy. Methods. A total of 100 patients were enrolled and allocated to receive 50 mg/kg vitamin C or placebo by intravenous infusion immediately after induction of anesthesia. Morphine consumption and scores of pain were assessed at 2, 6, and 24 h after completion of surgery. Results. There were 97 patients included in the analysis. Patients who received vitamin C had higher plasma concentrations of vitamin C at the end of surgery, significantly lower morphine consumption at the 2 h after end of surgery, and significantly lower pain scores at rest during first 24 h postoperatively. There was no significant difference between groups in side effects, fatigue score, or pain score during cough. Conclusion. This study shows high dose vitamin C infusion decreased postoperative pain during the first 24 h and reduced morphine consumption in the early postoperative period. Additional research needed to examine whether higher doses of vitamin C and longer infusion times can amplify these effects.

  18. Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C-propofol.

    Science.gov (United States)

    Simons, P J; Cockshott, I D; Douglas, E J; Gordon, E A; Hopkins, K; Rowland, M

    1988-04-01

    1. An intravenous dose of 14C-propofol (0.47 mg/kg) administered to six male volunteers was rapidly eliminated with 88% recovered in the urine in 5 days and less than 2% in faeces. 2. The dose was cleared by metabolism with less than 0.3% excreted unchanged. The major metabolites were the glucuronic acid conjugate of propofol and the glucuronic acid and sulphate conjugates of its hydroxylated derivative, 2,6-diisopropyl-1,4-quinol. Propofol glucuronide accounted for about 53% of the urinary radioactivity and was the major metabolite in plasma from 30 min post dose. 3. The blood concentration of propofol declined in a biphasic manner from a maximum mean value of 0.44 microgram/ml, 2 min after injection. The half-lives of the first and second exponential phases, mean values 5 min and 97 min respectively, varied widely among subjects. A proportion of the dose was cleared slowly, probably due to slow release from less well perfused tissues. Propofol accounted for 94% of the total blood radioactivity at 2 min but only about 6% from 3 to 8 h post dose. 4. Propofol has a volume of distribution equivalent to about 3 to 4 times body weight, and a mean total body clearance of 2.2 1/min.

  19. Does intravenous induction dosing among patients undergoing gastrointestinal surgical procedures follow current recommendations: a study of contemporary practice.

    Science.gov (United States)

    Akhtar, Shamsuddin; Liu, Jia; Heng, Joseph; Dai, Feng; Schonberger, Robert B; Burg, Matthew M

    2016-09-01

    It is recommended to correct intravenous induction doses by up to 50% for patients older than 65 years. The objectives were to determine (a) the degree to which anesthesia providers correct induction doses for age and (b) additionally adjust for American Society of Anesthesiologists physical status (ASA-PS) class (severity of illness) and (c) whether postinduction hypotension is more common among patients aged >65. Retrospective chart review. Academic medical center. A total of 1869 adult patients receiving general anesthesia for GI surgical procedures from February 2013 to January 2014. Patients were divided into 3 age groups (age 80, which was still in less than the recommendations. An inverse relationship was observed between propofol dosing and ASA-PS class, but no consistent relationship was noted for fentanyl and midazolam. There were a significantly larger drop in mean arterial pressure and a greater likelihood of hypotension following induction in patients aged 65-79 years and >80 years as compared with those aged <65 years. This study shows that the administered dose of anesthetic induction agents is significantly higher than that recommended for patients older than 65 years. This failure to age-adjust dose may contribute to hypotensive episodes. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. An Automated Inpatient Split-dose Bowel Preparation System Improves Colonoscopy Quality and Reduces Repeat Procedures.

    Science.gov (United States)

    Yadlapati, Rena; Johnston, Elyse R; Gluskin, Adam B; Gregory, Dyanna L; Cyrus, Rachel; Werth, Lindsay; Ciolino, Jody D; Grande, David P; Keswani, Rajesh N

    2017-07-19

    Inpatient colonoscopy preparations are often inadequate, compromising patient safety and procedure quality, while resulting in greater hospital costs. The aims of this study were to: (1) design and implement an electronic inpatient split-dose bowel preparation order set; (2) assess the intervention's impact upon preparation adequacy, repeated colonoscopies, hospital days, and costs. We conducted a single center prospective pragmatic quasiexperimental study of hospitalized adults undergoing colonoscopy. The experimental intervention was designed using DMAIC (define, measure, analyze, improve, and control) methodology. Prospective data collected over 12 months were compared with data from a historical preintervention cohort. The primary outcome was bowel preparation quality and secondary outcomes included number of repeated procedures, hospital days, and costs. On the basis of a Delphi method and DMAIC process, we created an electronic inpatient bowel preparation order set inclusive of a split-dose bowel preparation algorithm, automated orders for rescue medications, and nursing bowel preparation checks. The analysis data set included 969 patients, 445 (46%) in the postintervention group. The adequacy of bowel preparation significantly increased following intervention (86% vs. 43%; P<0.01) and proportion of repeated procedures decreased (2.0% vs. 4.6%; P=0.03). Mean hospital days from bowel preparation initiation to discharge decreased from 8.0 to 6.9 days (P=0.02). The intervention resulted in an estimated 1-year cost-savings of $46,076 based on a reduction in excess hospital days associated with repeated and delayed procedures. Our interdisciplinary initiative targeting inpatient colonoscopy preparations significantly improved quality and reduced repeat procedures, and hospital days. Other institutions should consider utilizing this framework to improve inpatient colonoscopy value.

  1. Pharmacokinetics of lansoprazole and its main metabolites after single and multiple intravenous doses in healthy Chinese subjects.

    Science.gov (United States)

    Zhang, Dan; Zhang, Yanan; Liu, Man; Wang, Xiaolin; Yang, Man; Han, Jing; Liu, Huichen

    2013-09-01

    The aim of the study was to evaluate and compare the pharmacokinetics of lansoprazole (LPZ) and its main metabolites, 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulfone (LPZS), after single and multiple intravenous (i.v.) doses of LPZ in healthy Chinese subjects. Twelve subjects (six males and six females) were given a single dose of LPZ by i.v. infusion on day 1, and multiple doses from day 2 to day 6. Blood samples were collected at designated time points for analysis of plasma concentrations of LPZ, HLPZ and LPZS by an LC-MS/MS method. LPZ was generally well tolerated in healthy Chinese subjects. After single and multiple i.v. doses of 30 mg LPZ, the C max values of LPZ, HLPZ and LPZS were 1490 ± 290 and 1450 ± 280, 175 ± 71 and 154 ± 56, and 51.3 ± 82.9 and 74.1 ± 158.7 ng/mL, with the AUC0-t values 3280 ± 2550 and 4260 ± 3880, 381 ± 128 and 389 ± 111, and 389 ± 1204 and 700 ± 2255 ng h/mL, respectively. The t 1/2 and CL values of LPZ after single and multiple i.v. doses were 1.48 ± 1.03 and 2.19 ± 1.03 h, and 11.67 ± 4.49 and 9.56 ± 4.08 L/h, respectively. Compared with the pharmacokinetics of LPZ after a single dose, t 1/2 increased markedly, CL decreased significantly and AUC increased by over 20 % after multiple doses. The results indicated that there was drug accumulation of LPZ after multiple i.v. doses, and there was no gender-related difference in pharmacokinetics of LPZ and its two metabolites.

  2. Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

    Science.gov (United States)

    Alam, Nausheen; Najam, Rahila

    2015-01-01

    Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

  3. Clinical evaluation of the hypoxic cytotoxin tirapazamine (SR-4233): phase I experience with repeated dose administration during fractionated irradiation

    International Nuclear Information System (INIS)

    Hancock, Steven L.; Spencer, Sharon; Mariscal, Carol; Wooten, Ann; Wheeler, Richard; Brown, J. Martin; Fisher, Cheryl; Roemeling, Reinhard von

    1996-01-01

    Purpose: Regions of chronic or transient hypoxia are common in many human tumors and are thought to limit tumor cell killing and tumor control with conventional irradiation and some chemotherapeutic agents. Tirapazamine (3-amino-1,2,4-benzotriazine-1,4-di-N-oxide) forms a cytotoxic free radical during reductive metabolism in regions of hypoxia. In well oxygenated regions, the tirapazamine radical reacts with molecular oxygen to form the inactive parent drug. This results in markedly greater toxicity for hypoxic cells than for the well oxygenated cells that comprise most normal tissues. Tirapazamine increased the anti-tumor effects of single dose or fractionated irradiation or cis-platin chemotherapy in murine tumors,in vivo . This study evaluated the ability to repeat the administration of Tirapazamine during courses of fractionated irradiation in humans after an earlier phase I trial established a maximum tolerated dose of 390 mg per square meter of body surface area (mg/m 2 ) when given as a single dose with radiotherapy. Materials and Methods: Between December 1993 and August 1995 22 patients with locally advanced or metastatic tumors of varying histology, normal renal, hepatic, and hematologic functions, and Karnofsky performance status ≥ 60 received repeated doses of Tirapazamine during a planned, 6 weeks course of standardly fractionated radiotherapy. After anti-emetic treatment with ondansetron (32 mg) and dexamethasone (16 mg), Tirapazamine was administered during a 2 hour intravenous infusion that ended from 30 to 90 minutes before a radiation treatment. Patients were monitored for acute toxicity during the course of treatment and for a minimum of one month after radiotherapy. Results: The study was initiated with three, biweekly doses of Tirapazamine at 330 mg/m 2 . Four of 7 patients who initiated treatment at this dose refused the second (1 patient) or third dose of Tirapazamine (3 patients). Two of the three patients who received three doses

  4. Non-ST Elevation Myocardial Infraction after High Dose Intravenous Immunoglobulin Infusion

    Directory of Open Access Journals (Sweden)

    Meir Mizrahi

    2009-01-01

    Full Text Available Intravenous immunoglobulins (IVIgs are used for several indications, including autoimmune conditions. IVIg treatment is associated with several possible adverse reactions including induction of a hypercoagulable state. We report a 76-year-old woman treated with IVIg for myasthenia gravis, which developed chest pain and weakness following IVIg infusion. The symptoms were associated with ST segment depression in V4–6 and elevated troponin levels. The patient was diagnosed with non-ST elevation myocardial infarction (NSTEMI. The patient had no significant risk factor besides age and a cardiac perfusion scan was interpreted as normal (the patient refused to undergo cardiac catheterization. This case is compatible with IVIg-induced hypercoagulability resulting in NSTEMI. Cardiac evaluation should therefore be considered prior to initiation of IVIg treatment especially in patients with multiple cardiovascular risks.

  5. Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series

    Directory of Open Access Journals (Sweden)

    Fligou Fotini

    2010-03-01

    Full Text Available Abstract Introduction Tetanus rarely occurs in developed countries, but it can result in fatal complications including respiratory failure due to generalized muscle spasms. Magnesium infusion has been used to treat spasticity in tetanus, and its effectiveness is supported by several case reports and a recent randomized controlled trial. Case presentations Three Caucasian Greek men aged 30, 50 and 77 years old were diagnosed with tetanus and admitted to a general 12-bed intensive care unit in 2006 and 2007 for respiratory failure due to generalized spasticity. Intensive care unit treatment included antibiotics, hydration, enteral nutrition, early tracheostomy and mechanical ventilation. Intravenous magnesium therapy controlled spasticity without the need for additional muscle relaxants. Their medications were continued for up to 26 days, and adjusted as needed to control spasticity. Plasma magnesium levels, which were measured twice a day, remained in the 3 to 4.5 mmol/L range. We did not observe hemodynamic instability, arrhythmias or other complications related to magnesium therapy in these patients. All patients improved, came off mechanical ventilation, and were discharged from the intensive care unit in a stable condition. Conclusion In comparison with previous reports, our case series contributes the following meaningful additional information: intravenous magnesium therapy was used on patients already requiring mechanical ventilation and remained effective for up to 26 days (significantly longer than in previous reports without significant toxicity in two patients. The overall outcome was good in all our patients. However, the optimal dose, optimal duration and maximum safe duration of intravenous magnesium therapy are unknown. Therefore, until more data on the safety and efficacy of magnesium therapy are available, its use should be limited to carefully selected tetanus cases.

  6. Dosing of Intravenous Tocilizumab in a Real-World Setting of Rheumatoid Arthritis: Analyses from the Corrona Registry.

    Science.gov (United States)

    Pappas, Dimitrios A; John, Ani; Curtis, Jeffrey R; Reed, George W; Karki, Chitra; Magner, Robert; Kremer, Joel M; Shewade, Ashwini; Greenberg, Jeffrey D

    2016-06-01

    In the United States, the recommended starting dose of intravenous tocilizumab (TCZ) is 4 mg/kg every 4 weeks, with an increase to 8 mg/kg based on clinical response for patients with moderate to severe rheumatoid arthritis; however, data on how TCZ dose is escalated in real life are missing. The objective of this analysis was to describe patterns of early intravenous TCZ dose escalation in a real-world setting using data from the Corrona registry. All patients enrolled in the comparative effectiveness substudy (CERTAIN) nested within Corrona who initiated TCZ and completed 3- and 6-month study visits were eligible for inclusion. Patients who initiated TCZ 4 mg/kg were categorized into 1 of 2 groups: those who remained on TCZ 4 mg/kg at 3 months (Group 1) and those who escalated to TCZ 8 mg/kg by or at 3 months (Group 2). Changes in clinical disease activity measures were provided. Of the 213 patients who were eligible for analysis, 86 (40.4%) remained on their initial dose of TCZ 4 mg/kg (Group 1) and 110 (51.6%) were escalated to TCZ 8 mg/kg by or at 3 months (Group 2). Baseline demographic and clinical characteristics were similar between the 2 groups; except in Group 2, patients were older (58.3 vs. 54.0 years) and a lower proportion was female (75.5% vs. 89.4%) than in Group 1. Significant improvements in disease activity measures were observed at 3 and 6 months in both groups, with the majority of patients in both groups achieving moderate or good European League Against Rheumatism response. Real-world data demonstrated that physicians escalate TCZ dose at varying frequencies. The ability to administer TCZ in varying doses allows physicians to tailor TCZ therapy to disease activity. ClinicalTrials.gov identifier, NCT01625650.

  7. Low-Dose Intravenous Paracetamol for Patent Ductus Arteriosus in Indomethacin-Resistant or Contraindicated Preterm Infants: Three Cases Reports.

    Science.gov (United States)

    Matsumura, Shun; Oshima, Ayumi; Fujinuma, Sumie; Tanaka, Kosuke; Nagano, Nobuhiko; Miyake, Fuyu; Masutani, Satoshi; Tamura, Masanori; Ueda, Keiko; Namba, Fumihiko

    2017-10-01

    Background  Although indomethacin (IND) is the standard treatment for hemodynamically significant patent ductus arteriosus (hsPDA) in Japan, it may be associated with renal impairment and gastrointestinal complications. The use of paracetamol for hsPDA closure has recently increased. Unlike IND, paracetamol does not have a peripheral vasoconstrictive effect and can be given to infants with contraindications to IND. Based on limited data available from randomized trials, paracetamol and IND seem to have similar effects. However, there have been no reports of the use of paracetamol for hsPDA in Japan. Cases  Our drug administration protocol was approved by the institutional ethics committee after purchasing a clinical trial insurance. In three premature infants in whom IND was contraindicated or ineffective, a 7.5 mg/kg of paracetamol was intravenously administered every 6 hour for 3 days after obtaining parental consents. A temporary hsPDA closure was observed in two of the three infants. However, all three infants eventually needed surgical closure. No side effects, such as hepatic and renal dysfunctions, and adverse events were reported. Conclusion  The intravenous administration of paracetamol was safe and feasible in premature infants with hsPDA. Future clinical trials with optimized dose and timing of administration are needed.

  8. Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid

    2015-01-01

    1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. METHODS/DESIGN: In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard...... Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant...... randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside...

  9. Repeated-dose effects of mequitazine, cetirizine and dexchlorpheniramine on driving and psychomotor performance.

    Science.gov (United States)

    Theunissen, Eef L; Vermeeren, Annemiek; Ramaekers, Johannes G

    2006-01-01

    Previous studies have demonstrated that the antihistamines mequitazine, cetirizine and dexchlorpheniramine produce mild sedation after single doses. It is unknown, however, whether acute sedation persists after repeated dosing. Therefore, this study assessed the effects of repeated dosing of these antihistamines on driving and psychomotor performance. Sixteen healthy volunteers were treated with mequitazine 10 mg q.a.m., cetirizine 10 mg q.a.m., dexchlorpheniramine Repetab 6 mg b.i.d. and placebo for four separate 8-day periods. Drug effects were assessed on days 1 and 8 using on-the-road driving tests (highway driving and car following), psychomotor tests (tracking and divided attention) and subjective questionnaires. Dexchlorpheniramine and mequitazine significantly impaired driving performance on the highway driving test on the first day; dexchlorpheniramine increased Standard Deviation of Lateral Position by 2 cm [95% confidence interval (CI) 0.5, 3.8] and mequitazine by 2.5 cm (CI 1.0, 4.3). These effects on driving performance disappeared after 8 days of treatment. No effect of treatment was found on car following, tracking and divided attention. Although subjective ratings confirmed that subjects knew their driving had been impaired in the mequitazine and dexchlorpheniramine condition after completion of the highway driving test on day 1, they did not expect their driving to be affected before the start of the test. Cetirizine did not impair performance on any of the tests. Single doses of mequitazine 10 mg and dexchlorpheniramine Repetab 6 mg cause mild driving impairment. However, when taken over several days, the impairing effect wears off, possibly as a result of tolerance.

  10. Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.

    Science.gov (United States)

    Serrano-Rodríguez, Juan Manuel; Gómez-Díez, Manuel; Esgueva, María; Castejón-Riber, Cristina; Mena-Bravo, Antonio; Priego-Capote, Feliciano; Ayala, Nahúm; Caballero, Juan Manuel Serrano; Muñoz, Ana

    2017-10-01

    Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3-4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48h. Additional research on benazepril administration in equine patients is indicated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Specific dose-dependent damage of Lieberkuehn crypts promoted by large doses of type 2 ribosome-inactivating protein nigrin b intravenous injection to mice

    International Nuclear Information System (INIS)

    Gayoso, M.J.; Munoz, R.; Arias, Y.; Villar, R.; Rojo, M.A.; Jimenez, P.; Ferreras, J.M.; Aranguez, I.; Girbes, T.

    2005-01-01

    Nigrin b is a non-toxic type 2 ribosome-inactivating protein as active as ricin at ribosomal level but 10 5 and 5 x 10 3 times less toxic for animal cell cultures and mice, respectively, than ricin. The purpose of the present study was to analyze the effects of intravenous injection of large amounts of nigrin b to the mouse. Injection through the tail vein of 16 mg/kg body weight killed all mice studied before 2 days. Analysis of several major tissues by light microscopy did not reveal gross nigrin b-promoted changes, except in the intestines which appeared highly damaged. As a consequence of the injury, the villi and crypt structures of the small intestine disappeared, leading to profuse bleeding and death. In contrast, intravenous injection of 5 mg/kg body weight was not lethal to mice but did trigger reversible toxic effects. In both cases, lethal and sub-lethal doses, the target of nigrin b appeared to be the highly proliferating stem cells of the intestinal crypts, which had undergone apoptotic changes. In contrast to nigrin b, the injection of 3 μg/kg of ricin kills all mice in 5 days but does not trigger apoptosis in the crypts. Therefore, the effect seen with sub-lethal nigrin b concentrations seems to be specific. Nigrin b killed COLO 320 human colon adenocarcinoma cells with an IC 50 of 3.1 x 10 -8 M and the effect was parallel to the extent of DNA fragmentation of these cells. Accordingly, despite the low general toxicity exerted by nigrin b as compared with ricin, intravenous injection of large amounts of nigrin b is able to kill mouse intestinal stem cells without threatening the lives of the animals, thereby opening a door for its use for the targeting of intestinal stem cells

  12. Pharmacokinetics of taurolidine following repeated intravenous infusions measured by HPLC-ESI-MS/MS of the derivatives taurultame and taurinamide in glioblastoma patients.

    Science.gov (United States)

    Stendel, Ruediger; Scheurer, Louis; Schlatterer, Kathrin; Stalder, Urs; Pfirrmann, Rolf W; Fiss, Ingo; Möhler, Hanns; Bigler, Laurent

    2007-01-01

    Taurolidine is known to have antimicrobial activity. Furthermore, at lower concentrations, it has been found to exert a selective antineoplastic effect in vitro and in vivo. The aim of this study was to investigate the pharmacokinetics of taurolidine in vivo following repeated intravenous infusion in a schedule used for the treatment of glioblastoma. As a prerequisite, the pharmacokinetics of taurolidine in human blood plasma and whole blood in vitro was investigated. The pharmacokinetics of taurolidine and its derivatives taurultame and taurinamide were investigated in human blood plasma and in whole blood in vitro using blood from a healthy male volunteer. During repeated intravenous infusion therapy with taurolidine, plasma samples were taken every hour for a period of 13 hours per day in seven patients (three male, four female; mean age 48.4 +/- 12.8 years, range 27-66 years) with a glioblastoma. Following dansyl derivatisation, the concentrations of taurultame and taurinamide were determined using a new method based on high-performance liquid chromatography (HPLC) online coupled to electrospray ionisation tandem mass spectrometry (ESI-MS/MS) in the multiple reaction monitoring mode. Under the experimental conditions used, taurolidine could not be determined directly and was back-calculated from the taurultame and taurinamide values. The new HPLC-ESI-MS/MS method demonstrated high accuracy and reproducibility. In vitro plasma concentrations of taurultame and taurinamide remained constant over the incubation period. In whole blood in vitro, a time-dependent formation of taurinamide was observed. At the start of the incubation, the taurultame-taurinamide ratio (TTR) was 0.95 at an initial taurolidine concentration of 50 microg/mL, and 1.69 at 100 microg/mL. The concentration of taurultame decreased at the same rate as the taurinamide concentration increased, showing logarithmic kinetics. The calculated taurolidine concentration remained largely constant over the

  13. Serum toxicokinetics after intravenous and oral dosing of larkspur toxins in goats

    Science.gov (United States)

    Poisoning of cattle by larkspur plants (Delphinium spp.) is a concern for cattle ranchers in western North America. Previous research studies have evaluated the toxicokinetic profile of multiple larkspur toxins in several livestock species. However, those studies were all performed by orally dosing ...

  14. Cerebrospinal fluid concentrations of vincristine after bolus intravenous dosing - A surrogate marker of brain penetration

    NARCIS (Netherlands)

    Kellie, SJ; Barbaric, D; Koopmans, P; Earl, J; Carr, DJ

    2002-01-01

    BACKGROUND. Vincristine (VCR) is used widely in oncology practice, and regular dosing is commonly associated with the development of sensorimotor or autonomic neuropathies. However, the incidence of VCR-related central nervous system (CNS) toxicity is comparatively low, suggesting that the

  15. Accidental intravenous infusion of a large dose of magnesium sulphate during labor: A case report

    Directory of Open Access Journals (Sweden)

    Kamal Kumar

    2013-01-01

    Full Text Available During labor and child delivery, a wide range of drugs are administered. Most of these medications are high-alert medications, which can cause significant harm to the patient due to its inadvertent use. Errors could be caused due to unfamiliarity with safe dosage ranges, confusion between similar looking drugs, mislabeling of drugs, equipment misuse, or malfunction and communication errors. We report a case of inadvertent infusion of a large dose of magnesium sulphate in a pregnant woman.

  16. Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

    Science.gov (United States)

    Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

    2015-02-01

    Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

  17. Single and repeated dose pharmacokinetics of dexketoprofen trometamol in patients with impaired liver function.

    Science.gov (United States)

    Valles, J; Artigas, R; Bertolotti, M; Crea, A; Muller, F; Paredes, I; Capriati, A

    2006-06-01

    Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. They received 25 mg dexketoprofen (equivalent to 37 mg of its tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8 hours for a total of 10 doses). Dexketoprofen concentrations were determined in plasma and urine by reverse-phase high performance liquid chromatography (HPLC). Model-independent pharmacokinetic parameters were obtained. All subjects completed the study. No serious adverse events were recorded. Following the single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects), 2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B). Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33-1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and 3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9 ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/- 0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration, similar results were obtained showing no drug accumulation. As related to the administered dose, median excretions of unchanged and conjugated dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy

  18. Effect of treatment with single total-dose intravenous iron versus daily oral iron(III-hydroxide polymaltose on moderate puerperal iron-deficiency anemia

    Directory of Open Access Journals (Sweden)

    Iyoke CA

    2017-05-01

    Full Text Available Chukwuemeka Anthony Iyoke,1 Fausta Chioma Emegoakor,1 Euzebus Chinonye Ezugwu,1 Lucky Osaheni Lawani,2 Leonard Ogbonna Ajah,1 Jude Anazoeze Madu,3 Hyginus Uzo Ezegwui,1 Frank Okechukwu Ezugwu4 1Department of Obstetrics and Gynaecology, University of Nigeria, Enugu Campus, 2Department of Obstetrics and Gynaecology, Federal Teaching Hospital, Abakaliki, 3Department of Haematology, University of Nigeria, Nsukka, 4Department of Obstetrics and Gynaecology, College of Medicine, Enugu State University, Enugu, Nigeria Background: Iron-deficiency anemia is the most common nutritional cause of anemia in pregnancy and is often responsible for puerperal anemia. Puerperal anemia can impair postpartum maternal and neonatal well-being. Objective: To determine the effect of treatment of moderate puerperal iron-deficiency anemia using a single intravenous total-dose iron dextran versus daily single dose oral iron(III-hydroxide polymaltose. Methodology: A randomized controlled study in which postpartum women with moderate iron-deficiency anemia were randomized into treatment with either a single total-dose intravenous iron dextran or with daily single doses of oral iron(III-hydroxide polymaltose tablets for 6 weeks. Effects on hemoglobin concentration using either method were compared at 6 weeks postpartum. Analysis was per protocol using SPSS version 17 for windows. P-values ≤0.05 were considered significant. Results: Two hundred eighty-four women were recruited for the study: 142 women received single total dose intravenous infusion of iron dextran while 142 received daily oral iron(III-hydroxide polymaltose tablets. Approximately 84.0% (237/282 completed the study and were analyzed including 81% (115/142 of those randomized to injectable iron therapy compared to 85.9% (122/142 of those randomized to oral treatment. The proportions of women who had attained hemoglobin concentration of at least 10 g/dL by the 6 weeks postpartum visit did not differ

  19. Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial.

    Science.gov (United States)

    Paridaans, Noortje P; Kamphuis, Marije M; Taune Wikman, Agneta; Tiblad, Eleonor; Van den Akker, Eline S; Lopriore, Enrico; Challis, Daniel; Westgren, Magnus; Oepkes, Dick

    2015-01-01

    Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e., 0.5 g/kg. This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 10(9)/l (range 8-269) in the 0.5 g/kg group versus 110 × 10(9)/l (range 11-279) in the 1 g/kg group (p = 0.644). The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

  20. Study of four week repeated dose toxic test of Sweet Bee Venom in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jae-Seuk Park

    2010-12-01

    Full Text Available Objectives: This study was performed to analyse four week repeated dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of four week repeated dose toxicity of Sweet BV which was administered at the level of 0.56㎎/㎏ body weight which is eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups were appealed pain sense in the treating time compared to the control group, and hyperemia and movement disorder were observed around the area of administration in all experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. In the urine analysis, CBC and biochemistry didn't show any significant changes in the experiment groups compared with control group. 5. For weight measurement of organs, experiment groups didn't show any significant changes compared with control group. 6. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, cerebrum, liver, lung, kidney, and spinal cords were removed and conducted histologocal observation with H-E staining. In the histologocal observation of thigh muscle, cell infiltration, inflammatory, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes were depend on the dose of Sweet BV. But another organs were not detected in any abnormalities. 7

  1. Effect of antiarrhythmic therapy with intravenous loading dose of amiodarone: evidence for an altered response in diabetic patients.

    Science.gov (United States)

    Iervasi, G; Clerico, A; Bonini, R; Nannipieri, M; Manfredi, C; Sabatino, L; Biagini, A; Donato, L

    1998-01-01

    Amiodarone, a potent class III antiarrhythmic agent with adrenergic antagonism properties, is administered increasingly to diabetic patients with cardiac arrhythmias refractory to all other available forms of therapy. Because a large percentage of diabetic patients show a perturbed autonomic regulation of the cardiovascular system, including a pertubed regulation of heart rate, we studied the antiarrhythmic response as well as the early effects (within 5 days) on heart rate of an intravenous amiodarone loading dose in diabetic patients. Seven type II (noninsulin-dependent) diabetic patients (age 64.7 +/- 9.7 years), affected by uncontrolled atrial fibrilation or atrial flutter, were enrolled for the study and a group of 12 well-matched (for age, sex and arrhythmia) nondiabetic patients served as a control group. It was found that before amiodarone administration, nondiabetic patients showed significantly wider variations in the circadian rhythm of heart rate values than diabetic patients (p = 0.0062, unpaired t-test). In all patients but one (who was nondiabetic), amiodarone treatment resulted in a cardioversion to sinus rhythm. After amiodarone administration, nondiabetic patients showed a significantly greater decrease (p = 0.0011) in heart rate values in comparison with the diabetic group (-35% vs. -20% on average, at the end of the study). Furthermore, in nondiabetic patients there was also an earlier significant fall (within the first 4 h after the start of treatment with amiodarone, p atrial fibrilation or atrial flutter may be delayed in comparison with nondiabetic patients. This altered response may be (at least in part) due to the diabetic autonomic neuropathy. Our study indicates that the presence of diabetes mellitus always must be taken into account when patients are enrolled for large, prospective, randomized trials, planned to evaluate the antiarrhythmic effects of amiodarone given intravenously.

  2. Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients

    NARCIS (Netherlands)

    Rook, Elisabeth J.; van Ree, Jan M.; van den Brink, Wim; Hillebrand, Michel J. X.; Huitema, Alwin D. R.; Hendriks, Vincent M.; Beijnen, Jos H.

    2006-01-01

    A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon"

  3. Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

    Science.gov (United States)

    Richter, C; Schnabel, A; Csernok, E; De Groot, K; Reinhold-Keller, E; Gross, W L

    1995-07-01

    In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.

  4. Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice

    Directory of Open Access Journals (Sweden)

    Pushkor Mukerji

    2015-01-01

    Full Text Available 6:2 fluorotelomer alcohol (6:2 FTOH was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL for systemic toxicity was 25 mg/kg/day (males and 5 mg/kg/day (females, based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell, clinical chemistry (liver-related, liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland. However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

  5. Low-dose intravenous ketamine for postcardiac surgery pain: Effect on opioid consumption and the incidence of chronic pain.

    Science.gov (United States)

    Cogan, Jennifer; Lalumière, Geneviève; Vargas-Schaffer, Grisell; Deschamps, Alain; Yegin, Zeynep

    2017-01-01

    Recent meta-analyses have concluded that low-dose intravenous ketamine infusions (LDKIs) during the postoperative period may help to decrease acute and chronic postoperative pain after major surgery. This study aims to evaluate the level of pain at least 3 months after surgery for patients treated with a postoperative LDKI versus patients who were not treated with a postoperative LDKI. Administrative and Ethics Board approval were obtained for this study. We performed a retrospective chart review for all patients receiving LDKI, and equal number of age-, sex-, and surgery-matched patients who did not receive LDKI. Low-dose ketamine was prepared using 100 mg of ketamine in 100 ml of normal saline and run between 50 and 200 mcg/kg/h. We reviewed 115 patients with LDKI and 115 without LDKI. The average age was 63.1 years, 73% of the patients were men and sex was evenly distributed between LDKI and non-LDKI. The average duration of the ketamine infusions was 26.8 h with the average dose being 169.9 mg. At an average of 9 months after surgery, 42% of the ketamine group and 38% of the nonketamine group stated that they had had pain on discharge. Of these patients, 30% of the ketamine group and 26% of the nonketamine group still had pain at the time of the phone call. Women in both groups had more acute and chronic pain than men. These results show that LDKI does not promote a decrease in long-term postoperative pain.

  6. Single Intravenous Dose of Novel Flurbiprofen-Loaded Proniosome Formulations Provides Prolonged Systemic Exposure and Anti-inflammatory Effect.

    Science.gov (United States)

    Verma, Preeti; Prajapati, Sunil K; Yadav, Rajbharan; Senyschyn, Danielle; Shea, Peter R; Trevaskis, Natalie L

    2016-11-07

    Vesicular and colloidal delivery systems can be designed to control drug release spatially and temporally to improve drug efficacy and side effect profiles. Niosomes (vesicles prepared from nonionic surfactants in aqueous media) are gaining interest as an alternative vesicular delivery system as they offer advantages such as biocompatibility, chemical stability, low cost, high purity, and versatility. However, the physical stability of niosomes, like other vesicular systems, is limited by vesicle fusion, aggregation, and leakage. Proniosomes (dehydrated powder or gel formulations that spontaneously form niosomes on hydration with aqueous media) can overcome these physical stability problems and are more convenient for sterilization, storage, transport, distribution, and dosing. Proniosomes have mostly been explored for their potential to enhance transdermal and oral absorption. In this study we assess, for the first time, the potential for hydrated proniosomes to sustain systemic exposure and therapeutic effect after intravenous delivery. Proniosomes carrying the anti-inflammatory drug, flurbiprofen, were prepared by spraying different nonionic surfactants (span 20, span 40, and span 60 in varying ratios with span 80) and cholesterol onto a sorbitol carrier. The proniosome powders were characterized for surface morphology and flow properties. Niosome formation was assessed at three different hydration temperatures (25, 37, and 45 °C), and the niosomes were assessed for vesicle size, entrapment efficiency, and sterility. OLP proniosomes prepared with a high ratio of span 80 to span 20 were found to spontaneously form vesicles of small size and high drug loading on hydration with aqueous media. The OLP derived niosomes successfully sustained in vitro drug release, in vivo pharmacokinetics, and the anti-inflammatory effect of flurbiprofen in an acute (rat paw edema) model of inflammation when compared to a control solution formulation. The study demonstrates that

  7. The impact on coagulation of an intravenous loading dose in addition to a subcutaneous regimen of low-molecular-weight heparin in the initial treatment of acute coronary syndromes

    NARCIS (Netherlands)

    Bijsterveld, Nick R.; Moons, Arno H.; Meijers, Joost C. M.; Levi, Marcel; Büller, Harry R.; Peters, Ron J. G.

    2003-01-01

    OBJECTIVES We sought to quantify the impact of adding an intravenous loading dose to a subcutaneous regimen of enoxaparin in patients with an acute coronary syndrome (ACS). BACKGROUND It is unclear whether an intravenous (M loading dose of enoxaparin should be added to a subcutaneous (SQ) regimen in

  8. Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs.

    Science.gov (United States)

    Smith, C D; Lee, R B; Moran, A V; Sipos, M L

    2016-01-01

    Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period. Published by Elsevier Inc.

  9. A 28-Day Repeated Dose Toxicological Study of an Aqueous Extract of Morus Alba L.

    Science.gov (United States)

    Marx, Tennille K; Glávits, Róbert; Endres, John R; Palmer, Philip A; Clewell, Amy E; Murbach, Timothy S; Hirka, Gábor; Pasics, Ilona

    2016-11-01

    Morus alba L. (white mulberry) leaves are one of the oldest recognized traditional Chinese medicines. More recently, M alba leaves and their constituents, particularly iminosugars (or azasugars), have garnered attention for their ability to maintain normal blood glucose concentrations, an effect identified in both animal studies and human clinical trials. Reducose (Phynova Group Limited) is a commercial water-soluble extract of M alba leaves standardized to 5% 1-deoxynojirimycin (DNJ), an iminosugar with α-glucosidase inhibition properties. Although there is an extensive history of consumption of M alba leaves by humans and animals worldwide, suggesting that the leaves and their extracts have a relatively good safety profile, we are unaware of safety assessments on an extract containing a higher amount of DNJ than that occurs naturally. The current 28-day repeated dose oral toxicity study in rats, conducted according to Organisation for Economic Co-operation and Development guidelines, was carried out to assess the safety of Reducose. Male and female Hsd.Han Wistar rats (4 groups of 10 animals/sex) were administered Reducose via gavage at doses of 0, 1,000, 2,000 and 4,000 mg/kg body weight (bw)/d. No treatment-related mortality or adverse effects (per clinical observations, body weight/weight gain, food consumption, ophthalmoscopy, clinical pathology, gross pathology, organ weights, or histopathology) were observed, and no target organs were identified. The no observed adverse effect level was determined to be 4,000 mg/kg bw/d for both male and female rats, the highest dose tested. © The Author(s) 2016.

  10. Safety and Efficacy of Intravenous Clevidipine for the Perioperative Control of Acute Hypertension in Neurosurgical Patients: A Dose Update

    Directory of Open Access Journals (Sweden)

    Kristin I Brower

    2017-06-01

    Full Text Available Clevidipine is a third-generation dihydropyridine calcium channel blocker approved in 2008 by the Food and Drug Administration for parenteral therapy of arterial hypertension. The high degree of lipophilicity of clevidipine provides a rapid onset of action and ease of titration to reach the desired clinical effect. Since its introduction into clinical practice, clevidipine has been shown to be safe and effective for perioperative use in patients undergoing procedures in which rapid and effective blood pressure control is essential. In 2011, clevidipine received institutional approval for intraoperative use during neurosurgical procedures and for postoperative blood pressure control in the Post-Anesthesia Care Unit and Surgical Intensive Care Unit during the first 24 hours after surgery. This review describes the efficacy and safety of intravenous clevidipine in intraoperative blood pressure management during neurosurgical procedures in 11 patients over a period of 3 months. The evaluation revealed that lower rates of clevidipine infusion than previously documented in the literature achieved blood pressure control within the desired limits during surgery while avoiding dose-related adverse reactions.

  11. Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome: A Randomized Trial.

    Science.gov (United States)

    Goebel, Andreas; Bisla, Jatinder; Carganillo, Roy; Frank, Bernhard; Gupta, Rima; Kelly, Joanna; McCabe, Candy; Murphy, Caroline; Padfield, Nick; Phillips, Ceri; Sanders, Mark; Serpell, Mick; Shenker, Nick; Shoukrey, Karim; Wyatt, Lynne; Ambler, Gareth

    2017-10-03

    Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition. To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years. 1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756). 7 secondary and tertiary care pain management centers in the United Kingdom. 111 patients with moderate or severe CRPS of 1 to 5 years' duration. IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization. The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life. The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, -0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of -1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events. Results do not apply to patients who have had CRPS for less than 1 year or more

  12. Fracture during intravenous bisphosphonate treatment in a child with osteogenesis imperfecta: an argument for a more frequent, low-dose treatment regimen.

    Science.gov (United States)

    Biggin, Andrew; Briody, Julie N; Ormshaw, Elizabeth; Wong, Karen K Y; Bennetts, Bruce H; Munns, Craig F

    2014-01-01

    Intravenous bisphosphonate therapy is the mainstay of medical treatment in osteogenesis imperfecta (OI) and has been shown to increase bone mass, decrease bone pain, improve mobility, and reduce the incidence of fractures. Sclerotic metaphyseal lines parallel to the growth plate are seen on long bone radiographs following cyclical intravenous therapy. These areas create stress risers within the bone that may act as foci for subsequent fractures as exemplified in this clinical case. An 8-year-old girl with OI sustained a distal radial fracture following 3 years of treatment with 6-monthly intravenous zoledronate. Her diagnosis, response to treatment, and subsequent fracture at a sclerotic metaphyseal line is described. Peripheral quantitative computer tomography was used to characterise the presence of multiple stress risers at the distal forearm. Trabecular bone mineral density fluctuated from 34 to 126% compared to neighbouring 2-mm regions. There remain many unanswered questions about optimal bisphosphonate treatment regimens in children with OI. The formation of stress risers following intravenous bisphosphonate treatment raises the hypothesis that a more frequent and low-dose bisphosphonate regimen would provide more uniform dosing of bone in the growing child and reduce the likelihood of fractures compared to current treatment practices.

  13. Efficacy of Single-dose and 2-dose Intravenous Administration of Ramosetron in Preventing Postoperative Nausea and Vomiting After Laparoscopic Gynecologic Operation: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial.

    Science.gov (United States)

    Lee, Banghyun; Kim, Kidong; Suh, Dong Hoon; Shin, Hyun-Jung; No, Jae Hong; Lee, Jung Ryeol; Jee, Byung Chul; Hwang, Jung Won; Do, Sang Hwan; Kim, Yong Beom

    2017-06-01

    This randomized trial investigated whether a 2-dose administration of intravenous ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective than a single-dose administration in preventing postoperative nausea and vomiting (PONV) in 89 patients who were scheduled to undergo laparoscopic operation for benign gynecologic diseases and to receive intravenous patient-controlled analgesia for relief of postoperative pain. After assignment at a ratio of 1:1, intravenous ramosetron (0.3 mg) was initially administered at the end of skin closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were administered to the study and control groups, respectively, at 4 hours after the operation. The baseline and operative characteristics were similar between the groups. The incidence of PONV during the 24-hour period after operation which was assessed as the primary endpoint did not differ between the groups. No serious adverse events occurred in either group. A 2-dose administration of intravenous ramosetron may not be superior to a single-dose administration in preventing PONV in patients undergoing laparoscopic operation for benign gynecologic diseases.

  14. EFFECTS OF PREANESTHETIC SINGLE DOSE INTRAVENOUS DEXMEDETOMIDINE VERSUS FENTANYL ON HEMODYNAMIC RESPONSE TO ENDOTRACHEAL INTUBATION-A CLINICAL COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Chandita

    2015-12-01

    Full Text Available INTRODUCTION Many pharmacological agents have been evaluated in regards to their efficacy of blunting the adverse cardiovascular response to laryngoscopy and tracheal intubation. The aim of this study was to evaluate the efficacy of dexmedetomidine compared to fentanyl in blunting the haemodynamic response to laryngoscopy and intubation. METHOD Sixty patients were randomly allocated into two groups (30 patients in each group. The group D received intravenously 1 µgm/kg dexmedetomidine infusion and group F received 2µgm/kg fentanyl infusion. The study drugs were prepared in an identical looking container and were infused fifteen minutes prior to induction of anaesthesia. The study drugs were infused over a period of ten minutes and all the patients underwent a similar anaesthetics technique. Heart rate (HR and blood pressure (systolic, diastolic and mean blood pressure were noted at baseline, at the end of infusion of the study drugs, after induction of anaesthesia, immediately after laryngoscopy and intubation and at 1, 3, 5, 7 and 10 minutes after laryngoscopy and intubation. RESULTS HR significantly decreased in the group D when compared to group F immediately after study drug infusion and there was statistically significant reduction in heart rate for up to 5 min after intubation in both the groups. Although HR increased after intubation in both the groups, the magnitude was lower in the group D. In both the groups, laryngoscopy and intubation led to an increase in systolic, diastolic and mean arterial pressure; the magnitude was lower in the group D. CONCLUSION Dexmeditomidine (1µ/kg attenuates these untoward responses of laryngoscopy and intubation more effectively than fentanyl (2 µ/kg when administered as bolus dose in the pre-induction period of general anaesthesia.

  15. Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

    Directory of Open Access Journals (Sweden)

    Charles H King

    2011-09-01

    Full Text Available Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling.Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni-$211 (S. haematobium per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are

  16. Plasma concentrations of fenbendazole (FBZ and oxfendazole in alpacas (Lama pacos after single intravenous and oral dosing of FBZ

    Directory of Open Access Journals (Sweden)

    Lakritz J

    2015-02-01

    Full Text Available Jeffrey Lakritz,1 Daniel Linden,2 David E Anderson,3 Terri A Specht4 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA; 2Department of Agriculture and Engineering Technologies, College of Food, Agriculture and Environmental Sciences, The Ohio State University, Wooster, OH, USA; 3Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA; 4Four Star Veterinary Service, Chickasaw, OH, USA Abstract: The objective of this study was to determine plasma pharmacokinetics and bioavailability of fenbendazole (FBZ and oxfendazole (OFZ after intravenous (iv and oral administrations of FBZ (5 mg/kg to alpacas. Plasma concentrations of FBZ and OFZ after administration of FBZ iv and orally (5 mg/kg were determined by high-performance liquid chromatography with ultraviolet detection. Total clearance (CL of FBZ was 16.5±4 mL/kg/min (range: 4–31 mL/kg/min, and steady-state volume of distribution (Vdss was 3.3±1 L/kg (range: 1.7–7.4 L/kg. The terminal phase half-life of FBZ after iv administration was 5.9±3.8 hours (range: 0.8–20 hours. After oral administration, the FBZ terminal phase half-life was 23±5 hours (range: 9–37 hours and the systemic bioavailability of FBZ was 16%±6% (range: 1%–41%. Peak FBZ concentrations after oral administration were 0.13±0.05 µg/mL (range: 0.05–0.28 µg/mL at 10 hours (range: 8–12 hours. Peak plasma OFZ concentrations after oral dosing with FBZ (5 mg/kg were 0.14±0.05 µg/mL (0.05–0.3 µg/mL at 24±7 hours (range: 12–48 hours. FBZ clearance is lower in comparison to that of other species. Systemic availability of FBZ after oral administration is low after oral dosing. Metabolites of FBZ produced by alpacas are similar to those observed in other species. Keywords: bioavailability, benzimidazoles, camelid, pharmacokinetics

  17. Repeat Gamma-Knife Radiosurgery for Refractory or Recurrent Trigeminal Neuralgia with Consideration About the Optimal Second Dose.

    Science.gov (United States)

    Park, Seong-Cheol; Kwon, Do Hoon; Lee, Do Hee; Lee, Jung Kyo

    2016-02-01

    To investigate adequate radiation doses for repeat Gamma Knife radiosurgery (GKS) for trigeminal neuralgia in our series and meta-analysis. Fourteen patients treated by ipsilateral repeat GKS for trigeminal neuralgia were included. Median age of patients was 65 years (range, 28-78), the median target dose, 140-180). Patients were followed a median of 10.8 months (range, 1-151) after the second gamma-knife surgery. Brainstem dose analysis and vote-counting meta-analysis of 19 studies were performed. After the second gamma-knife radiosurgeries, pain was relieved effectively in 12 patients (86%; Barrow Neurological Institute Pain Intensity Score I-III). Post-gamma-knife radiosurgery trigeminal nerve deficits were mild in 5 patients. No serious anesthesia dolorosa was occurred. The second GKS radiation dose ≤ 60 Gy was significantly associated with worse pain control outcome (P = 0.018 in our series, permutation analysis of variance, and P = 0.009 in the meta-analysis, 2-tailed Fisher's exact test). Cumulative dose ≤ 140-150 Gy was significantly associated with poor pain control outcome (P = 0.033 in our series and P = 0.013 in the meta-analysis, 2-tailed Fisher's exact test). A cumulative brainstem edge dose >12 Gy tended to be associated with trigeminal nerve deficit (P = 0.077). Our study suggests that the second GKS dose is a potentially important factor. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Comparison of sedation and mechanical antinociception induced by intravenous administration of acepromazine and four dose rates of dexmedetomidine in donkeys.

    Science.gov (United States)

    Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Robinson, Lauren S

    2017-05-01

    To assess and compare the sedative and antinociceptive effects of four dosages of dexmedetomidine in donkeys. Randomized, controlled, crossover, Latin-square, blinded study. Six healthy, castrated, adult, standard donkeys. Dexmedetomidine (2, 3, 4 and 5 μg kg -1 ; D2, D3, D4 and D5), acepromazine (0.1 mg kg -1 ) and saline were administered intravenously to each donkey and a 1 week interval was allowed between successive trials on each animal. Sedation scores (SS) and head heights above ground (HHAG) were used to assess sedation and mechanical nociceptive threshold (MNT) testing to assess antinociception over 120 minutes post-treatment. Areas under the curve (AUC) for 0-30, 30-60 and 60-120 minutes were computed to compare the effect of treatments. SS-AUC 0-30 values were larger for D4 and D5, and SS-AUC 30-60 values were larger for D5 than for saline. All dexmedetomidine treatments produced lower HHAG-AUC 0-30 and HHAG-AUC 30-60 values, and acepromazine produced lower HHAG AUC 60-120 values than did saline. For MNT, D3, D4 and D5 increased AUC 0-30 and AUC 30-60 values compared with saline and also AUC 0-30 values compared with D2 and acepromazine. Smaller MNT-AUC 30-60 values were obtained with D2 than with D4 and D5, with D3 than with D5, and with acepromazine than with D4 and D5. Dexmedetomidine induced sedation and dosage-dependent mechanical antinociception. Larger dexmedetomidine dose rates were required to induce antinociception than sedation. Furthermore, the antinociception induced by dexmedetomidine was of shorter duration than its sedation. For minor painful procedures on standing donkeys, D5 may be clinically useful to provide sedation and analgesia. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

  19. Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery

    Directory of Open Access Journals (Sweden)

    Shashi Kiran

    2011-01-01

    Full Text Available This study was undertaken to study efficacy of single dose of intravenous magnesium sulphate to reduce post-operative pain in patients undergoing inguinal surgery. One hundred patients undergoing inguinal surgery were divided randomly in two groups of 50 each. The patients of magnesium sulphate group (Group-I received magnesium sulphate 50 mg/kg in 250 ml of isotonic sodium chloride solution IV whereas patients in control group (Group-II received same volume of isotonic sodium chloride over 30 minutes preoperatively. Anaesthesia was induced with propofol (2 mg/kg and pethidine (1 mg/kg. Atracurium besylate (0.5 mg/kg was given to facilitate insertion of LMA. Pain at emergence from anaesthesia and 2, 4, 6, 12 and 24 hours after surgery was evaluated. The timing and dosage of rescue analgesic during first 24 hrs after operation was noted. Pain in postop period was significantly lower in magnesium sulphate group in comparison to control group at emergence from anaesthesia and 2, 4, 6, 12 and 24 hrs postop [1.86 vs. 1.96 (P=0.138, 1.22 vs. 1.82 (P=0.001, 1.32 vs. 1.88 (P=0.000, 2.74 vs. 3.84 (P=0.000, 1.36 vs. 2.00 (P=0.000 and 0.78 vs 1.30 (P=0.000, respectively]. Patients in group-I were more sedated as compared to group-II [sedation score 1.86 vs. 1.40 (P=0.000]. Rescue analgesia requirement postoperatively in first 4, 8 and 16 hrs was significantly lower in patients of group-1 than in group- II [1.9 vs. 3.8 (P<0.05, 25.50 vs. 52.50 (P<0.05 and 0.000 vs. 7.5 (P<0.05]. Preoperative magnesium sulphate infusion decreases postop pain and requirement of rescue analgesia.

  20. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

    Science.gov (United States)

    Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

    2018-01-20

    Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  1. Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

    Directory of Open Access Journals (Sweden)

    Jia Choi

    2018-01-01

    Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

  2. Effect of repeated small-dose γ-ray irradiation on atopic dermatitis in NC/Nga mice

    International Nuclear Information System (INIS)

    Fang, Su-Ping; Muto, Yasuko; Tago, Fumitoshi; Simura, Noriko; Kojima, Shuji

    2006-01-01

    We previously showed that several small-dose 0.5 Gy whole-body γ-ray irradiation inhibits tumor growth in mice via elevation of the interferon (IFN)-γ/interleukin 4 (IL-4) ratio concomitantly with a decrease in the percentage of B cells. Here, we examined whether repeated small-dose (0.5 Gy, 10 times) γ-ray irradiation influences atopic dermatitis in an NC/Nga mouse model. It was found that repeated γ-ray irradiation increased total IgE in comparison with the disease-control group. Levels of IL-4 and IL-5 were increased versus the disease-control group, while IFN-γ was slightly decreased, resulting in a further decrease of the IFN-γ/IL-4 ratio compared with the disease-control group. These results indicate that repeated small-dose γ-ray irradiation may exacerbate atopic dermatitis. This may be because the irradiation induces not helper T lymphocyte 1 (Th1), but Th2 polarization in this atopic mouse model, i.e., the effects of small-dose irradiation may be different in conditions involving immune hypersensitivity and impaired immunity. (author)

  3. Single-dose intravenous iron infusion versus red blood cell transfusion for the treatment of severe postpartum anaemia

    DEFF Research Database (Denmark)

    Holm, C; Thomsen, L L; Norgaard, A

    2017-01-01

    BACKGROUND AND OBJECTIVES: There are no randomized trials comparing intravenous iron to RBC transfusion for the treatment of severe postpartum anaemia. The objectives of this study were to evaluate the feasibility of randomizing women with severe postpartum anaemia secondary to postpartum...... haemorrhage to RBC transfusion or intravenous iron, and to describe patient-reported outcomes, and haematological and iron parameters. MATERIALS AND METHODS: Women with a postpartum haemorrhage exceeding 1000 ml and an Hb between 5·6 and 8·1 g/dl were randomized to 1500 mg of intravenous iron (n = 7......) isomaltoside or RBC transfusion (n = 6). Participants completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and blood samples were drawn at inclusion, daily during the first week and at weeks 3, 8 and 12. RESULTS: We screened 162 women and included 13 (8...

  4. Characterization of ornidazole metabolites in human bile after intraveneous doses by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry

    Directory of Open Access Journals (Sweden)

    Jiangbo Du

    2012-04-01

    Full Text Available Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS was used to characterize ornidazole metabolites in human bile after intravenous doses. A liquid chromatography tandem mass spectrometry (LC–MS/MS assay was developed for the determination of the bile level of ornidazole. Bile samples, collected from four patients with T-tube drainage after biliary tract surgery, were prepared by protein precipitation with acetonitrile before analysis. A total of 12 metabolites, including 10 novel metabolites, were detected and characterized. The metabolites of ornidazole in human bile were the products of hydrochloride (HCl elimination, oxidative dechlorination, hydroxylation, sulfation, diastereoisomeric glucuronation, and substitution of NO2 or Cl atom by cysteine or N-acetylcysteine, and oxidative dechlorination followed by further carboxylation. The bile levels of ornidazole at 12 h after multiple intravenous infusions were well above its minimal inhibitory concentration for common strains of anaerobic bacteria.

  5. Kinetics and dose calculations of ampicillin and gentamicin given as continuous intravenous infusion during parenteral nutrition in 88 newborn infants

    DEFF Research Database (Denmark)

    Colding, H; Møller, S; Bentzon, M W

    1983-01-01

    Ampicillin and gentamicin were administered continuously intravenously to 88 newborn infants using individually calculated dosages. For infants with a mean value of plasma clearance of the antibiotics, it was calculated that the serum ampicillin and gentamicin concentrations would be between 35-5...

  6. Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects.

    Science.gov (United States)

    Raffa, Robert B; Pawasauskas, Jayne; Pergolizzi, Joseph V; Lu, Luke; Chen, Yin; Wu, Sutan; Jarrett, Brant; Fain, Randi; Hill, Lawrence; Devarakonda, Krishna

    2018-03-01

    Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine. In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.125 mg/kg) at the 2nd and 3rd intervals. Comparisons of plasma pharmacokinetic profiles were conducted before, during, and after opioid co-administrations. Twenty-two subjects were included in the pharmacokinetic analysis. Observed paracetamol peak concentration (C max ) and area under the plasma concentration-time curve over the dosing interval (AUC 0-6 ) were reduced when oral paracetamol was co-administered with morphine (reduced from 11.6 to 7.25 µg/mL and from 31.00 to 25.51 µg·h/mL, respectively), followed by an abruptly increased C max and AUC 0-6 upon discontinuation of morphine (to 13.5 µg/mL and 52.38 µg·h/mL, respectively). There was also a significantly prolonged mean time to peak plasma concentration (T max ) after the 4th dose of oral paracetamol (2.84 h) compared to the 1st dose (1.48 h). However, pharmacokinetic parameters of paracetamol were not impacted when intravenous paracetamol was co-administered with morphine. Morphine co-administration significantly impacted the pharmacokinetics of oral but not intravenous paracetamol. The abrupt release of accumulated paracetamol at the end of morphine-mediated gastrointestinal inhibition following oral but not intravenous administration of paracetamol suggests that intravenous paracetamol provides a better option for the management of postoperative pain. CLINICALTRIALS. NCT02848729.

  7. Optimization of initial propofol bolus dose for EEG Narcotrend Index-guided transition from sevoflurane induction to intravenous anesthesia in children.

    Science.gov (United States)

    Dennhardt, Nils; Boethig, Dietmar; Beck, Christiane; Heiderich, Sebastian; Boehne, Martin; Leffler, Andreas; Schultz, Barbara; Sümpelmann, Robert

    2017-04-01

    Sevoflurane induction followed by intravenous anesthesia is a widely used technique to combine the benefits of an easier and less traumatic venipuncture after sevoflurane inhalation with a recovery with less agitation, nausea, and vomiting after total intravenous anesthesia (TIVA). Combination of two different anesthetics may lead to unwanted burst suppression in the electroencephalogram (EEG) during the transition phase. The objective of this prospective clinical observational study was to identify the optimal initial propofol bolus dose for a smooth transition from sevoflurane induction to TIVA using the EEG Narcotrend Index (NI). Fifty children aged 1-8 years scheduled for elective pediatric surgery were studied. After sevoflurane induction and establishing of an intravenous access, a propofol bolus dose range 0-5 mg·kg -1 was administered at the attending anesthetist's discretion to maintain a NI between 20 and 64, and sevoflurane was stopped. Anesthesia was continued as TIVA with a propofol infusion dose of 15 mg·kg -1 ·h -1 for the first 15 min, followed by stepwise reduction according to McFarlan's pediatric infusion regime, and remifentanil 0.25 μg·kg -1 ·min -1 . Endtidal concentration of sevoflurane, NI, and hemodynamic data were recorded during the whole study period using a standardized case report form. Propofol plasma concentrations were calculated using the paedfusor dataset and a TIVA simulation program. Median endtidal concentration of sevoflurane at the time of administration of the propofol bolus was 5.1 [IQR 4.7-5.9] Vol%. The median propofol bolus dose was 1.2 [IQR 0.9-2.5] mg·kg -1 and median NI thereafter was 33 [IQR 23-40]. Nine children presented with a NI 13-20 and three children with burst suppression in the EEG (NI 0-12); all of them received an initial propofol bolus dose >2 mg·kg -1 . Regression equation demonstrated that NI 20-64 was achieved with a 95% probability when using a propofol bolus dose of 1 mg·kg -1 after

  8. Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia.

    Science.gov (United States)

    Ramachandran, Balaji; Jayavelu, Subramani; Murhekar, Kanchan; Rajkumar, Thangarajan

    2016-01-01

    EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract) and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal)] and limited [p.o (oral)] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.

  9. Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia

    Directory of Open Access Journals (Sweden)

    Balaji Ramachandran

    Full Text Available EGCG (Epigallocatechin-3-gallate is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal] and limited [p.o (oral] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment. Keywords: EGCG, Green tea, Serum lipids, Dose dependant toxicity, Route dependant toxicity, Liver toxicity, Dyslipidemia

  10. Estimation of breast doses and breast cancer risk associated with repeated fluoroscopic chest examinations of women with tuberculosis

    International Nuclear Information System (INIS)

    Boice, J.D. Jr.; Rosenstein, M.; Trout, E.D.

    1978-01-01

    A methodology is presented to estimate cumulative breast dose and breast cancer risk for women exposed to repeated fluoroscopic chest examinations during air collapse therapy for pulmonary tuberculosis. Medical record abstraction, physician interview, patient contact, machine exposure measurements, and absorbed dose computations were combined to estimate average breast doses for 1047 Massachusetts women who were treated between 1930 and 1954. The methodology presented considers breast size and composition, patient orientation, x-ray field size and location, beam quality, type of examination, machine exposure rate, and exposure time during fluoroscopic examinations. The best estimate for the risk of radiation-induced cancer for the women living longer than 10 years after initial fluoroscopic exposure is 6.2 excess breast cancers per million woman-year-rad with 90% confidence limits of 2.8 and 10.7 cancers/10 6 WY-rad. When breast cancer risk is considered as a function of absorbed dose in the breast, instead of as a function of the number of fluoroscopic examinations, a linear dose--response relationship over the range of estimated doses is consistent with the data. However, because of the uncertainty due to small-sample variability and because of the wide range of assumptions regarding certain fluoroscopy conditions, other dose--response relationships are compatible with the data

  11. High dose Intravenous Anti-D Immune Globulin is More Effective and Safe in Indian Paediatric Patients of Immune Thrombocytopenic Purpura.

    Science.gov (United States)

    Swain, Trupti Rekha; Jena, Rabindra Kumar; Swain, Kali Prasanna

    2016-12-01

    Immune Thrombocytopenia (ITP) is characterised by an autoimmune antibody-mediated destruction of platelets and impaired platelet production. Few controlled trials exist to guide management of patients with ITP in Indian scenario for which patients require an individualized approach. Anti-D (Rho (D) immune globulin) at a higher dose can prove to be a cost effective and safe alternative for Indian patients with ITP. To compare the safety and efficacy of higher dose (75μg/kg) intravenous Anti-D immune globulin against the standard dose of 50μg/kg for the management of ITP in Indian patients. One hundred and sixty four children with newly diagnosed ITP between 4-14 years were randomly selected for inclusion and were treated with 50μg/kg (standard dose) or 75μg /kg (higher dose) of Anti-D to compare the efficacy and safety of higher dose intravenous anti-D immune globulin. Efficacy of Anti-D was measured in terms of rate of response and median time to response for increase in platelet counts. Any adverse event was noted. A decrease in haemoglobin concentration suggested accompanying haemolysis. Seventy one out of 84 patients treated with Anti-D at 75μg/kg produced complete response (85%) with median time of response being 2.5 days. On the contrary, 45 patients (70%) patients treated with 50μg/kg had complete response. However, there was no significant increase in haemolysis with higher dose. A significant correlation was found between dose and peak increase in platelet count measured at 7 th day following administration. However, there was no relationship between the decrease in haemoglobin and the dose given, or between the increase in platelet count and fall in haemoglobin. A 75μg/kg dose of Anti-D is more effective with acceptable side effect in comparison to 50μg dose for treatment of newly diagnosed Indian patients of ITP.

  12. Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.

    Science.gov (United States)

    Wark, J D; Bensen, W; Recknor, C; Ryabitseva, O; Chiodo, J; Mesenbrink, P; de Villiers, T J

    2012-02-01

    Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p paracetamol or ibuprofen. Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.

  13. Comparison of postoperative analgesic efficacy of intraoperative single-dose intravenous administration of dexketoprofen trometamol and diclofenac sodium in laparoscopic cholecystectomy.

    Science.gov (United States)

    Anıl, Ali; Kaya, Fatma Nur; Yavaşcaoğlu, Belgin; Mercanoğlu Efe, Esra; Türker, Gürkan; Demirci, Abdurrahman

    2016-08-01

    The aim of this study is to compare the effects of intravenous single-dose dexketoprofen trometamol and diclofenac sodium 30 minutes before the end of the surgery on relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. A randomized fashion. Sixty (American Society of Anesthesiologist class I-II) patients undergoing laparoscopic cholecystectomy were divided into 2 groups Patients in group DT received 50 mg dexketoprofen trometamol, whereas patients in group DS received 75 mg diclofenac sodium, intravenously 30 minutes before the end of surgery. Postoperative pain intensity, morphine consumption with patient-controlled analgesia, time to first analgesic requirement, complications, rescue analgesic (intravenous tenoxicam 20 mg) requirement, and duration of hospital stay were recorded. Postoperative pain visual analog scale scores were similar in the follow-up periods (P > .05). Patient-controlled analgesia morphine consumption was significantly less in group DT compared with group DS in all postoperative follow-up periods (2 and 4 hours: P dexketoprofen trometamol 30 minutes before the end of surgery provided effective analgesia with reduced consumption of opioids and requirement for rescue analgesic compared with diclofenac sodium in patients undergoing laparoscopic cholecystectomy. For this reason, we believe that, as a part of multimodal analgesia, dexketoprofen trometamol provides more effective analgesia than diclofenac sodium in patients undergoing laparoscopic cholecystectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Late occurring lesions in the skin of rats after repeated doses of X-rays

    International Nuclear Information System (INIS)

    Hopewell, J.W.

    1985-01-01

    Late radiation damage, characterized by atrophy and necrosis in the skin and subcutaneous tissues, has been demonstrated in both the tail and feet of rats. The incidence of necrosis increased with total dose. These total doses, in the range 72-144 Gy, were given as 4-8 treatment of 18 Gy, each dose separated from the next by an interval of 28 days. This treatment protocol minimized acute epithelial skin reactions. The same regime applied to the skin on the back of rats resulted in a very severe acute reaction occurring after the second to fifth dose of 18 Gy. This was surprising since back skin, like tail skin, is less sensitive to large single doses of radiation than that of the foot. The late radiation reaction in the foot and tail of rats are compared and contrasted with other attempts to assess late effects in rodent skin and with late changes seen in pig skin. (author)

  15. Median Lethal Doses Associated with Intravenous Exposure to the Optically Pure Enantiomers of VX in Guinea Pigs

    Science.gov (United States)

    2017-03-01

    in Guinea Pigs 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Wright, Linnzi K. M.; Forster, Jeffry S...intravenous exposure of adult, male guinea pigs to the individual VX enantiomers, and we compared those potencies to that for a racemic mixture. The P...highly toxic based on the U.S. Environmental Protection Agency’s Acute Toxicity Categories for Pesticide Products. 15. SUBJECT TERMS Guinea pig

  16. Physiologic effect of repeated adrenaline (epinephrine) doses during cardiopulmonary resuscitation in the cath lab setting: A randomised porcine study.

    Science.gov (United States)

    Hardig, Bjarne Madsen; Götberg, Michael; Rundgren, Malin; Götberg, Matthias; Zughaft, David; Kopotic, Robert; Wagner, Henrik

    2016-04-01

    This porcine study was designed to explore the effects of repetitive intravenous adrenaline doses on physiologic parameters during CPR. Thirty-six adult pigs were randomised to four injections of: adrenaline 0.02 mg(kgdose)(-1), adrenaline 0.03 mg(kgdose)(-1) or saline control. The effect on systolic, diastolic and mean arterial blood pressure, cerebral perfusion pressure (CePP), end tidal carbon dioxide (ETCO2), arterial oxygen saturation via pulse oximetry (SpO2), cerebral tissue oximetry (SctO2), were analysed immediately prior to each injection and at peak arterial systolic pressure and arterial blood gases were analysed at baseline and after 15 min. In the group given 0.02 mg(kgdose)(-1), there were increases in all arterial blood pressures at all 4 pressure peaks but CePP only increased significantly after peak 1. A decrease in ETCO2 following peak 1 and 2 was observed. SctO2 and SpO2 were lowered following injection 2 and beyond. In the group given a 0.03 mg(kgdose)(-1), all ABP's increased at the first 4 pressure peaks but CePP only following 3 pressure peaks. Lower ETCO2, SctO2 and SpO2 were seen at peak 1 and beyond. In the two adrenaline groups, pH and Base Excess were lower and lactate levels higher compared to baseline as well as compared to the control. Repetitive intravenous adrenaline doses increased ABP's and to some extent also CePP, but significantly decreased organ and brain perfusion. The institutional protocol number: Malmö/Lund Committee for Animal Experiment Ethics, approval reference number: M 192-10. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Cognitive enhancement and antipsychotic-like activity following repeated dosing with the selective M4 PAM VU0467154.

    Science.gov (United States)

    Gould, Robert W; Grannan, Michael D; Gunter, Barak W; Ball, Jacob; Bubser, Michael; Bridges, Thomas M; Wess, Jurgen; Wood, Michael W; Brandon, Nicholas J; Duggan, Mark E; Niswender, Colleen M; Lindsley, Craig W; Conn, P Jeffrey; Jones, Carrie K

    2018-01-01

    Although selective activation of the M 1 muscarinic acetylcholine receptor (mAChR) subtype has been shown to improve cognitive function in animal models of neuropsychiatric disorders, recent evidence suggests that enhancing M 4 mAChR function can also improve memory performance. Positive allosteric modulators (PAMs) targeting the M 4 mAChR subtype have shown therapeutic potential for the treatment of multiple symptoms observed in schizophrenia, including positive and cognitive symptoms when assessed in acute preclinical dosing paradigms. Since the cholinergic system has been implicated in multiple stages of learning and memory, we evaluated the effects of repeated dosing with the highly selective M 4 PAM VU0467154 on either acquisition and/or consolidation of learning and memory when dosed alone or after pharmacologic challenge with the N-methyl-d-aspartate subtype of glutamate receptors (NMDAR) antagonist MK-801. MK-801 challenge represents a well-documented preclinical model of NMDAR hypofunction that is thought to underlie some of the positive and cognitive symptoms observed in schizophrenia. In wildtype mice, 10-day, once-daily dosing of VU0467154 either prior to, or immediately after daily testing enhanced the rate of learning in a touchscreen visual pairwise discrimination task; these effects were absent in M 4 mAChR knockout mice. Following a similar 10-day, once-daily dosing regimen of VU0467154, we also observed 1) improved acquisition of memory in a cue-mediated conditioned freezing paradigm, 2) attenuation of MK-801-induced disruptions in the acquisition of memory in a context-mediated conditioned freezing paradigm and 3) reversal of MK-801-induced hyperlocomotion. Comparable efficacy and plasma and brain concentrations of VU0467154 were observed after repeated dosing as those previously reported with an acute, single dose administration of this M 4 PAM. Together, these studies are the first to demonstrate that cognitive enhancing and antipsychotic

  18. Oral pyridoxine can substitute for intravenous pyridoxine in managing patients with severe poisoning with isoniazid and rifampicin fixed dose combination tablets: a case report.

    Science.gov (United States)

    Dilrukshi, M D S A; Ratnayake, C A P; Gnanathasan, C A

    2017-08-08

    Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had

  19. Pharmacokinetic evaluation of pamidronate after oral administration: a study on dose proportionality, absolute bioavailability, and effect of repeated administration

    DEFF Research Database (Denmark)

    Hyldstrup, Lars; Flesch, G; Hauffe, S A

    1993-01-01

    30 minutes at constant infusion rate. Repeated peroral doses (75 and 150 mg) were administered to 12 females (aged 51-70 years) for 10 consecutive days. Urinary excretion of pamidronate after peroral and i.v. administration was used for estimation of pamidronate absorption. Renal excretion...... of pamidronate ranged from 0.01% to 0.35% of dose, with mean values of 0.11, 0.16, and 0.18% for 75, 150, and 300 mg, respectively. After i.v. infusion, the renal excretion of pamidronate was 26-53% of the dose, lower than for other bisphosphonates. The absolute bioavailability was 0.31% (range 0.08-0.7%) after...

  20. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Science.gov (United States)

    2010-07-01

    ... considered necessary. The limit test applies except when human exposure indicates the need for a higher dose..., stereotypies (e.g., excessive grooming, repetitive circling) or bizarre behaviour (e.g., self-mutilation...

  1. Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.

    Science.gov (United States)

    Viscardi, Rose M; Othman, Ahmed A; Hassan, Hazem E; Eddington, Natalie D; Abebe, Elias; Terrin, Michael L; Kaufman, David A; Waites, Ken B

    2013-05-01

    Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial

  2. Repeated-dose toxicological studies of Tithonia diversifolia (Hemsl.) A. gray and identification of the toxic compounds.

    Science.gov (United States)

    Passoni, Flávia Donaire; Oliveira, Rejane Barbosa; Chagas-Paula, Daniela Aparecida; Gobbo-Neto, Leonardo; Da Costa, Fernando Batista

    2013-05-20

    Tithonia diversifolia (Hemsl.) A. Gray has been commonly used in folk medicine to treat abscesses, microbiological infections, snake bites, malaria and diabetes. Both anti-inflammatory and anti-malarial properties have been identified using appropriate assays, but the effective doses have demonstrated toxic effects for the experimental animals. Most of the pharmacological activities have been attributed to sesquiterpene lactones (STLs) and some chlorogenic acid derivatives (CAs) in the leaves of this species. This work aimed to evaluate the repeated-dose toxicity of an aqueous extract (AE) from Tithonia diversifolia leaves and to compare the results with an extract rich in STLs (LRE) and a polar extract (PE) without STLs but rich in CAs. The purpose of this work was to provide insights into the identity of the compounds responsible for the toxic effects of Tithonia diversifolia. The major classes of compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling using previously isolated or standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The AE is composed of both STLs and CAs, the LRE is rich in STLs, and the PE is rich in CAs. The AE caused alterations in haematological parameters but few alterations in biochemical parameters and was relatively safe at doses lower than 100mg/kg. However, the PE and LRE demonstrated several adverse effects by damaging the liver and kidneys, respectively. STLs and CAs can be toxic in prolonged use at higher doses in extracts prepared from Tithonia diversifolia by affecting the kidneys and liver. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

    Science.gov (United States)

    Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2017-09-01

    The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  4. A 12-week dose-escalating study of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese hemodialysis patients
.

    Science.gov (United States)

    Yokoyama, Keitaro; Fukagawa, Masafumi; Shigematsu, Takashi; Akiba, Takashi; Fujii, Akifumi; Odani, Motoi; Akizawa, Tadao

    2017-08-01

    To evaluate dose-escalation of etelcalcetide (ONO-5163/AMG 416), a novel, intravenous (IV), long-acting calcium-sensing receptor agonist, for treatment of secondary hyperparathyroidism (SHPT) in Japanese hemodialysis patients. In this multicenter study, IV injections of etelcalcetide (3 times a week for 12 weeks) were administered, with dose escalation every 4 weeks depending on changes in serum intact parathyroid hormone (iPTH) and corrected calcium (cCa). A total of 24 patients participated in this study. Serum iPTH was reduced in a time- and dose-dependent manner, with reductions (in pg/mL) at 12 weeks of -226.1 ± 125.3, -362.5 ± 161.5, and -412.4 ± 130.2, respectively, for maximum doses of 5, 10, and 15 mg. At the end of the treatment, 50% of patients had serum iPTH levels within the target range (60 - 240 pg/mL). Serum cCa and phosphorus were reduced in parallel with iPTH. Adverse events (AEs) occurred in 20 patients (83.3%). The most frequently observed AEs (> 10%) were either mild or moderate nasopharyngitis (29.2%), decreased serum calcium (16.7%), and vomiting (12.5%). Dose-escalated triweekly etelcalcetide was effective for SHPT in Japanese hemodialysis patients and was satisfactorily tolerated.
.

  5. Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

    Directory of Open Access Journals (Sweden)

    Ramaswamy Ramaswamy

    2012-10-01

    Full Text Available Abstract Background Nuna Kadugu (NK, a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats

  6. Comparison of the Concentrations of Lidocaine in Different Body Fluids/Tissues after Subarachnoid Space and Intravenous Administration of a Lethal Dose of Lidocaine

    Directory of Open Access Journals (Sweden)

    Nan Zhang

    2015-01-01

    Full Text Available The objective of the study was to compare the concentration of lidocaine in different body fluids/tissues after subarachnoid space and intravenous administrations of a lethal dose of lidocaine. Totally 18 dogs were used in the experiment. Six dogs were given subarachnoid anesthesia, another were given an intravenous injection of a dose of 75 mg/kg weight of lidocaine hydrochloride in 5 min and the last 6 dogs were used as the blank control dogs and given a subarachnoid space injection or a femoral artery injection of the same volume of sodium chloride. As soon as its vital signs disappeared, each dog was dissected and the specimen, such as brain, cerebrospinal fluid (CSF in lateral ventricle, CSF in subarachnoid space, spinal cord (cervical spinal cord, thoracic spinal cord, lumbar spinal cord, and waist spinal cord, heart, lung, liver, spleen, kidney, bile, urine, heart blood, peripheral blood, muscle in injection location, and muscle in no injection location, were collected for analysis of lidocaine immediately. Analysis was performed with gas chromatography-mass spectrometry (GC-MS. From the maximum to the minimum, the order of lidocaine concentration detected in the subarachnoid space-administered dogs was as follows: CSF in subarachnoid space, waist spinal cord, thoracic spinal cord, CSF in lateral ventricle, lumbar spinal cord, cervical spinal cord, lung, kidney, muscle in injection location, heart, brain, spleen, heart blood, liver, peripheral blood, bile, muscle in no injection location, and urine. The order of lidocaine concentration detected in the intravenously administered dogs was as followed: Kidney, heart, lung, spleen, brain, liver, peripheral blood, bile, heart blood, cervical spinal cord, thoracic spinal cord, muscle in injection location, lumbar spinal cord, muscle in no injection location, CSF in subarachnoid space, urine, and CSF in lateral ventricle. The maximum concentration of lidocaine was detected in the subarachnoid

  7. Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

    Science.gov (United States)

    Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

    2018-04-01

    Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

  8. Urinary calculi composed of uric acid, cystine, and mineral salts: differentiation with dual-energy CT at a radiation dose comparable to that of intravenous pyelography.

    Science.gov (United States)

    Thomas, Christoph; Heuschmid, Martin; Schilling, David; Ketelsen, Dominik; Tsiflikas, Ilias; Stenzl, Arnulf; Claussen, Claus D; Schlemmer, Heinz-Peter

    2010-11-01

    To retrospectively evaluate radiation dose, image quality, and the ability to differentiate urinary calculi of differing compositions by using low-dose dual-energy computed tomography (CT). The institutional review board approved this retrospective study; informed consent was waived. A low-dose dual-energy CT protocol (tube voltage and reference effective tube current-time product, 140 kV and 23 mAs and 80 kV and 105 mAs; collimation, 64 × 0.6 mm; pitch, 0.7) for the detection of urinary calculi was implemented into routine clinical care. All patients (n = 112) who were examined with this protocol from July 2008 to August 2009 were included. The composition of urinary calculi was assessed by using commercially available postprocessing software and was compared with results of the reference standard (ex vivo infrared spectroscopy) in 40 patients for whom the reference standard was available. Effective doses were calculated. Image quality was rated subjectively and objectively and was correlated with patient size expressed as body cross-sectional area at the level of acquisition by using Spearman correlation coefficients. One calcified concrement in the distal ureter of an obese patient was mistakenly interpreted as mixed calcified and uric acid. One struvite calculus was falsely interpreted as cystine. All other uric acid, cystine, and calcium-containing calculi were correctly identified by using dual-energy CT. The mean radiation dose was 2.7 mSv. The average image quality was rated as acceptable, with a decrease in image quality in larger patients. Low-dose unenhanced dual-source dual-energy CT can help differentiate between calcified, uric acid, and cystine calculi at a radiation dose comparable to that of conventional intravenous pyelography. Because of decreased image quality in obese patients, only nonobese patients should be examined with this protocol. © RSNA, 2010.

  9. The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs.

    Science.gov (United States)

    Honkavaara, J M; Restitutti, F; Raekallio, M R; Kuusela, E K; Vainio, O M

    2011-08-01

    Different doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, with or without dexmedetomidine were compared in conscious dogs. Eight animals received either dexmedetomidine (10 μg/kg [D]), MK-467 (250 μg/kg [M250] or dexmedetomidine (10 μg/kg) with increasing doses of MK-467 (250 μg/kg [DM250], 500 μg/kg [DM500] and 750 μg/kg [DM750], respectively). Treatments were given intravenously (i.v.) in a randomized, crossover design with a 14-day washout period. Systemic hemodynamics and arterial blood gas analyses were recorded at baseline and at intervals up to 90 min after drugs administration. Dexmedetomidine alone decreased heart rate, cardiac index and tissue oxygen delivery and increased mean arterial pressure and systemic vascular resistance 5 min after administration. DM250 did not completely prevent these early effects, while DM750 induced a decrease in mean arterial pressure. With DM500, systemic hemodynamics remained stable throughout the observational period. MK-467 alone increased cardiac index and tissue oxygen delivery and had no deleterious adverse effects. No differences in arterial blood gases were observed between treatments that included dexmedetomidine. It was concluded that MK-467 attenuated or prevented dexmedetomidine's systemic hemodynamic effects in a dose-dependent manner when given simultaneously i.v. but had no effect on the pulmonary outcome in conscious dogs. A 50:1 dose ratio (MK-467:dexmedetomidine) induced the least alterations in cardiovascular function. © 2010 Blackwell Publishing Ltd.

  10. A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Sae-Rom Yoo

    2017-01-01

    Full Text Available Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT, a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

  11. Evaluation of the repeated-dose liver micronucleus assay using 2,4-dinitrotoluene: a report of a collaborative study by CSGMT/JEMS.MMS.

    Science.gov (United States)

    Maeda, Akihisa; Tsuchiyama, Hiromi; Asaoka, Yoshiji; Hirakata, Mikito; Miyoshi, Tomoya; Oshida, Keiyu; Miyamoto, Yohei

    2015-03-01

    The liver micronucleus assay using young adult rats has the potential to detect liver carcinogens by repeated dosing, and could be expected to be integrated into repeated-dose toxicity studies using a hepatocyte isolation method without the traditional in situ collagenase perfusion. In this study, to assess the performance of the repeated-dose liver micronucleus assay, 2,4-dinitrotoluene (DNT), which is a rodent liver carcinogen, was administered orally to male rats at doses of 50, 100 and 200 mg/kg/day once daily for 14 or 28 consecutive days, and the frequencies of micronucleated hepatocytes (MNHEPs) and micronucleated immature erythrocytes (MNIMEs) were examined. Significant increases in the MNHEPs were observed at 50 mg/kg/day or more in the 14-day treatment, and 50 and 100 mg/kg/day in the 28-day treatment. These increases were dependent on both the dose and the number of administrations, which indicates the possibility that the MNHEPs accumulate as a result of repeated dosing. In contrast, no increase in the MNIMEs was observed. In conclusion, the repeated-dose liver micronucleus assay using young adult rats is sufficiently sensitive to detect the genotoxicity of 2,4-DNT at a low dose.

  12. The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing.

    Science.gov (United States)

    Kohonen, Pekka; Benfenati, Emilio; Bower, David; Ceder, Rebecca; Crump, Michael; Cross, Kevin; Grafström, Roland C; Healy, Lyn; Helma, Christoph; Jeliazkova, Nina; Jeliazkov, Vedrin; Maggioni, Silvia; Miller, Scott; Myatt, Glenn; Rautenberg, Michael; Stacey, Glyn; Willighagen, Egon; Wiseman, Jeff; Hardy, Barry

    2013-01-01

    The aim of the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing-1) research cluster, comprised of seven EU FP7 Health projects co-financed by Cosmetics Europe, is to generate a proof-of-concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT-1 strategy is to adopt a mode-of-action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross-cluster infrastructure project whose activities include the development of a data warehouse to provide a web-accessible shared repository of research data and protocols, a physical compounds repository, reference or "gold compounds" for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA-Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. A flow-cytometric NK-cytotoxicity assay adapted for use in rat repeated dose toxicity studies

    International Nuclear Information System (INIS)

    Marcusson-Staahl, Maritha; Cederbrant, Karin

    2003-01-01

    A recent regulatory document for immunotoxicity testing of new pharmaceutical drugs includes cytotoxic natural killer (NK)-cell function as a required parameter in repeated dose toxicity studies. The classical 51 Cr-release assay is the conventional test for cytotoxicity testing but several drawbacks with this assay has increased the demand for new reliable test systems. Here, we describe the optimisation of a flow-cytometric cytotoxicity assay especially adapted for regulatory rat studies in drug development. The test principle is based on target cell labelling with 5-(6)-carboxy-fluorescein succinimidyl ester (CFSE) and subsequent DNA-labelling with propidium iodide (PI) for identification of target cells with compromised cell membranes. The results are expressed as percentage of dead targets on a cell-to-cell basis. The final format of the assay includes 0.5 ml peripheral blood, 1.25x10 5 effector cells per sample, and collection of 500 target events by flow-cytometry. When NKR-P1+ cells were removed from the effector cell population by magnetic depletion the relative proportion decreased from 6 to 0.08%. The corresponding cytotoxic activity decreased from 68 to 8%. Also, the cytotoxic activity showed a significant and positive correlation with the proportion of NK-cells present in the effector cell suspension. Thus, the cytotoxicity measured is almost exclusively exerted by NK-cells. The current flow-cytometric test benefits from using peripheral blood as a source for effector cells since it will not conflict with the use of spleen for histopathological investigations in repeated dose toxicity studies. Additionally, since only a minimal number of effector cells are required per sample repeated testing of the same animal is enabled

  14. The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta.

    Science.gov (United States)

    Biggin, Andrew; Zheng, Linda; Briody, Julie N; Coorey, Craig P; Munns, Craig F

    2015-01-01

    Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy. A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods. Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI. © 2015 S. Karger AG, Basel.

  15. Open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of intravenously administered CNF1010 (17-(allylamino)-17-demethoxygeldanamycin [17-AAG]) in patients with solid tumors.

    Science.gov (United States)

    Saif, M W; Erlichman, C; Dragovich, T; Mendelson, D; Toft, D; Burrows, F; Storgard, C; Von Hoff, D

    2013-05-01

    17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin that binds to and inhibits the Hsp90 family of molecular chaperones leading to the proteasomal degradation of client proteins critical in malignant cell proliferation and survival. We have undertaken a Phase 1 trial of CNF1010, an oil-in-water nanoemulsion of 17-AAG. Patients with advanced solid tumors and adequate organ functions received CNF1010 by 1-h intravenous (IV) infusion, twice a week, 3 out of 4 weeks. Doses were escalated sequentially in single-patient (6 and 12 mg/m(2)/day) and three-to-six-patient (≥25 mg/m(2)/day) cohorts according to a modified Fibonacci's schema. Plasma pharmacokinetic (PK) profiles and biomarkers, including Hsp70 in PBMCs, HER-2 extracellular domain, and IGFBP2 in plasma, were performed. Thirty-five patients were treated at doses ranging from 6 to 225 mg/m(2). A total of 10 DLTs in nine patients (2 events of fatigue, 83 and 175 mg/m(2); shock, abdominal pain, ALT increased, increased transaminases, and pain in extremity at 175 mg/m(2); extremity pain, atrial fibrillation, and metabolic encephalopathy at 225 mg/m(2)) were noted. The PK profile of 17-AAG after the first dose appeared to be linear up to 175 mg/m(2), with a dose-proportional increase in C max and AUC0-inf. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects of CNF1010 at doses >83 mg/m(2). The maximum tolerated dose was not formally established. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects. The CNF1010 clinical program is no longer being pursued due to the toxicity profile of the drug and the development of second-generation Hsp90 molecules.

  16. Intravenous administration of high-dose Paclitaxel reduces gut-associated lymphoid tissue cell number and respiratory immunoglobulin A concentrations in mice.

    Science.gov (United States)

    Moriya, Tomoyuki; Fukatsu, Kazuhiko; Noguchi, Midori; Okamoto, Koichi; Murakoshi, Satoshi; Saitoh, Daizoh; Miyazaki, Masaru; Hase, Kazuo; Yamamoto, Junji

    2014-02-01

    Chemotherapy remains a mainstay of treatment for cancer patients. However, anti-cancer drugs frequently cause a wide range of side effects, including leukopenia and gastrointestinal toxicity. These adverse effects can lead to treatment delays or necessitate temporary dose reductions. Although chemotherapy-related changes in gut morphology have been demonstrated, the influences of chemotherapeutic regimens on gut immunity are understood poorly. This study aimed to examine whether the anti-cancer drug paclitaxel (PTX) impairs gut immunity in mice. Male ICR mice were randomized into three groups: Control, low-dose PTX (low PTX; 2 mg/kg), or high-dose PTX (high PTX; 4 mg/kg). A single intravenous dose was given. On day seven after the injection, lymphocytes from Peyer patches (PP), intraepithelial (IE) spaces, and the lamina propria (LP) were counted and analyzed by flow cytometry (CD4(+), CD8(+), αβTCR(+), γδTCR(+), B220(+)). Immunoglobulin A (IgA) concentrations were measured in small intestinal and respiratory tract washings. Total, CD4(+) and γδTCR(+) lymphocyte numbers in PPs were significantly lower in the high PTX than in the control group. The CD4(+) lymphocyte numbers in the IE spaces were significantly lower in both PTX groups than in the control group. Respiratory tract IgA concentrations were lower in the high PTX than in the control group. The present data suggest high-dose PTX impairs mucosal immunity, possibly rendering patients more vulnerable to infection. Careful dose selection and new therapies may be important for maintaining mucosal immunity during PTX chemotherapy.

  17. Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a multiple ascending dose study in opioid-naïve healthy volunteers.

    Science.gov (United States)

    Rauck, Richard L; Oh, D Alexander; Singla, Neil; Koch, Christian; Parikh, Neha; Nalamachu, Srinivas; Wilson, Daniel; Yu, Jin; Vetticaden, Santosh

    2017-11-01

    Fentanyl sublingual spray, with its rapid onset for pain relief, may be efficacious in the management of acute or post-operative pain. Because patients in these settings may be opioid-naïve, the study was conducted to determine the safety, tolerability, and pharmacokinetics of multiple dose administration of fentanyl sublingual spray in an opioid-naïve population. Fentanyl sublingual spray (100 mcg, 200 mcg, and 400 mcg) and fentanyl citrate intravenous (IV; 50 mcg) were administered every 0.5, 1.0, 2.0, and 4.0 h for up to three doses per cohort in opioid-naïve subjects (ClinicalTrials.gov identifier: NCT02641340). Eight subjects in each cohort were randomly assigned (six subjects received fentanyl sublingual spray; two subjects received fentanyl citrate IV). Pharmacokinetic and safety-related pharmacodynamic assessments were performed through 24 h post-first dose. Safety assessments were collected through Day 7. Ninety-six opioid-naïve subjects, aged 20-55 years, with a body mass index of 18.7-31.5 kg/m 2 , participated in the study. Multiple doses of fentanyl sublingual spray (100, 200, and 400 mcg) were generally well tolerated. Hypoxia, observed in the 200-mcg and 400-mcg dose groups, increased with increasing doses and higher dosing frequency, but was readily managed by nasal cannula oxygenation. Overall, nausea increased with increasing doses, and ∼52.6% (10 out of 19) cases of nausea that occurred at the highest dose of 400 mcg were treated with concomitant medication. Overall, the reported adverse events were consistent with the known safety profile of fentanyl. Fentanyl sublingual spray (100 mcg, 200 mg, and 400 mcg) administered every 0.5, 1, 2, and 4 h was generally well tolerated in an opioid-naïve population. The results suggest that doses of 200 mcg or lower may be safe for use in an opioid-naïve population.

  18. Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

    Science.gov (United States)

    Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi

    2012-05-01

    A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

  19. A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

    Science.gov (United States)

    Andrews, Chasity D; Yueh, Yun Lan; Spreen, William R; St Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D; Markowitz, Martin

    2015-01-14

    Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP. Copyright © 2015, American Association for the Advancement of Science.

  20. Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination.

    Science.gov (United States)

    Schneider, M; Paulin, A; Dron, F; Woehrlé, F

    2014-12-01

    The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  1. Association between low-dose pulsed intravenous cyclophosphamide therapy and amenorrhea in patients with systemic lupus erythematosus: A case-control study

    Science.gov (United States)

    2011-01-01

    Background The risk for amenorrhea following treatment of systemic lupus erythematosus (SLE) patients with low-dose intravenous cyclophosphamide (IVCY) has not been fully explored. Our objective was to ascertain the incidence of amenorrhea following treatment with low-dose IVCY and the association between amenorrhea and the clinical parameters of SLE. Methods A case-control retrospective study of premenopausal women ≤ 45 years old who had been treated for SLE with low-dose IVCY (500 mg/body/pulse) plus high-dose glucocorticoids (0.8-1.0 mg/kg/day of prednisolone; IVCY group) or glucocorticoids alone (0.8-1.0 mg/kg/day of prednisolone; steroid group) in our hospital from 2000 through 2009 was conducted using a questionnaire survey and medical record review. Results Twenty-nine subjects in the IVCY group and 33 subjects in the steroid group returned the questionnaire. A multivariate analysis revealed that age at initiation of treatment ≥ 40 years old was significantly associated with amenorrhea [p = 0.009; odds ratio (OR) 10.2; 95% confidence interval (CI) 1.8-58.7]. IVCY treatment may display a trend for association with amenorrhea (p = 0.07; OR 2.9; 95% CI 0.9-9.4). Sustained amenorrhea developed in 4 subjects in the IVCY group and 1 subject in the steroid group; all of these patients were ≥ 40 years old. Menses resumed in all subjects amenorrhea, our data suggest that patients amenorrhea with low-dose IVCY treatment. A higher risk for sustained amenorrhea following treatment with IVCY is a consideration for patients ≥ 40 years old. PMID:21663683

  2. Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH.

    Science.gov (United States)

    Schmitt-Hoffmann, Anne; Desai, Amit; Kowalski, Donna; Pearlman, Helene; Yamazaki, Takao; Townsend, Robert

    2016-08-01

    Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.

  3. Early intravenous immunoglobin (two-dose regimen) in the management of severe Rh hemolytic disease of newborn--a prospective randomized controlled trial.

    Science.gov (United States)

    Elalfy, Mohsen Saleh; Elbarbary, Nancy Samir; Abaza, Heba Wegdan

    2011-04-01

    Phototherapy is the standard treatment in moderately severe hemolytic disease of newborn (HDN), whereas exchange transfusion (ET) is the second line in progressive cases. Intravenous immunoglobin (IVIG) has been suggested to decrease the need for ET. We aimed at assessing the efficacy of early two-dose regimens of IVIG to avoid unnecessary ET in severe Rh HDN. The study included 90 full-term neonates with Rh incompatibility unmodified by antenatal treatment and not eligible for early ET and which were randomly assigned into one of three groups: group (I), treated by conventional method; groups IIa and IIb received IVIG once at 12 h postnatal age if PT was indicated, in a dose of 0.5 and 1 g/kg, respectively. Analysis revealed 11 neonates (22%) in the conventional group and 2 (5%) in the intervention group who administered low-dose IVIG at 12 h, while none in group IIb required exchange transfusion (p = 0.03). Mean bilirubin levels were significantly lower during the first 96 h in the intervention group compared to the conventional group (p < 0.0001). Shorter duration of phototherapy (52.8 ± 12.39 h) and hospital stay (3.25 ± 0.71 days) in the IVIG group compared to conventional group (84 ± 12.12 h and 4.72 ± 0.78 days, p < 0.0001, respectively) were observed. We conclude that IVIG administration at 12 h was effective in the treatment of severe Rh HDN; the low-dose IVIG (0.5 g/kg) was as effective as high dose (1 g/kg) in reducing the duration of phototherapy and hospital stay, but less effective in avoiding exchange transfusion.

  4. Comparison of distribution and toxicity following repeated oral dosing of different vanadium oxide nanoparticles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Jung, E-mail: pejtoxic@hanmail.net [Myunggok Eye Research Institute, Konyang University, Daejeon 302-718 (Korea, Republic of); Lee, Gwang-Hee [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of); Yoon, Cheolho [Seoul Center, Korea Basic Science Institute, Seoul 126-16 (Korea, Republic of); Kim, Dong-Wan, E-mail: dwkim1@korea.ac.kr [School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul 136-713 (Korea, Republic of)

    2016-10-15

    Vanadium is an important ultra-trace element derived from fuel product combustion. With the development of nanotechnology, vanadium oxide nanoparticles (VO NPs) have been considered for application in various fields, thus the possibility of release into the environment and human exposure is also increasing. Considering that verification of bioaccumulation and relevant biological responses are essential for safe application of products, in this study, we aimed to identify the physicochemical properties that determine their health effects by comparing the biological effects and tissue distribution of different types of VO NPs in mice. For this, we prepared five types of VO NPs, commercial (C)-VO{sub 2} and -V{sub 2}O{sub 5} NPs and synthetic (S)-VO{sub 2}, -V{sub 2}O{sub 3,} and -V{sub 2}O{sub 5} NPs. While the hydrodynamic diameter of the two types of C-VO NPs was irregular and impossible to measure, those of the three types of S-VO NPs was in the range of 125–170 nm. The S- and C-V{sub 2}O{sub 5} NPs showed higher dissolution rates compared to other VO NPs. We orally dosed the five types of VO NPs (70 and 210 μg/mouse, approximately 2 and 6 mg/kg) to mice for 28 days and compared their biodistribution and toxic effects. We found that S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs more accumulated in tissues compared to other three types of VO NPs, and the accumulated level was in order of heart>liver>kidney>spleen. Additionally, tissue levels of redox reaction-related elements and electrolytes (Na{sup +}, K{sup +}, and Ca{sup 2+}) were most clearly altered in the heart of treated mice. Notably, all S- and C-VO NPs decreased the number of WBCs at the higher dose, while total protein and albumin levels were reduced at the higher dose of S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs. Taken together, we conclude that the biodistribution and toxic effects of VO NPs depend on their dissolution rates and size (surface area). Additionally, we suggest that further studies

  5. Pharmacokinetics of repeated oral doses of amlodipine and amlodipine plus telmisartan in healthy volunteers.

    Science.gov (United States)

    Stangier, J; Su, C A

    2000-12-01

    This open-label, crossover study was performed to establish if there is evidence for interaction between telmisartan, an angiotensin II antagonist, and amlodipine, a class II (dihydropyridine) calcium channel antagonist, on the basis of pharmacokinetics and safety. In a two-way crossover trial, 12 healthy Caucasian males were randomized to receive once daily for 9 days oral amlodipine 10 mg with or without oral telmisartan 120 mg. After a washout period of > or = 13 days, the subjects were switched to the other medication regimen. The geometric means of the primary pharmacokinetic parameters at steady state (day 9) for amlodipine when given alone were the following: maximum plasma concentration (Cmax) 17.7 ng/mL, area under the plasma concentration-time curve (AUC) 331 ng.h/mL, and renal clearance 39.5 mL/min, with 8% of the total amlodipine dose being excreted. When concomitant telmisartan was given, the respective values were 18.7 ng/mL, 352 ng.h/mL, and 43.0 mL/min, with 9.4% of the total amlodipine dose being excreted renally. The limits of the 90% confidence intervals (CIs) for the ratios of these steady-state parameters were 0.97 to 1.14 for Cmax and 0.98 to 1.16 for AUC; both were within the predefined reference range (0.8 to 1.25) for bioequivalence. The high intersubject variability in urinary amlodipine excretion resulted in bioequivalence not being demonstrated for renal clearance. Adverse effects were few, mild to moderate in intensity, and transient whether amlodipine was given alone or with telmisartan. Vital signs, except for blood pressure, and clinical laboratory values were unaffected by either medication. The findings of this study show that concomitant telmisartan and amlodipine may be administered as there is no clinically significant variation in primary pharmacokinetic parameters of amlodipine in the presence of telmisartan, and the safety of the combination is comparable to that of amlodipine alone.

  6. Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

    Directory of Open Access Journals (Sweden)

    M. D. Jegoda

    2013-06-01

    Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

  7. Screening of repeated dose toxicity data present in SCC(NF)P/SCCS safety evaluations of cosmetic ingredients.

    Science.gov (United States)

    Vinken, Mathieu; Pauwels, Marleen; Ates, Gamze; Vivier, Manon; Vanhaecke, Tamara; Rogiers, Vera

    2012-03-01

    Alternative methods, replacing animal testing, are urgently needed in view of the European regulatory changes in the field of cosmetic products and their ingredients. In this context, a joint research initiative called SEURAT was recently raised by the European Commission and COLIPA, representing the European cosmetics industry, with the overall goal of developing an animal-free repeated dose toxicity testing strategy for human safety assessment purposes. Although cosmetic ingredients are usually harmless for the consumer, one of the initial tasks of this research consortium included the identification of organs that could potentially be affected by cosmetic ingredients upon systemic exposure. The strategy that was followed hereof is described in the present paper and relies on the systematic evaluation, by using a self-generated electronic databank, of published reports issued by the scientific committee of DG SANCO responsible for the safety of cosmetic ingredients. By screening of the repeated dose toxicity studies present in these reports, it was found that the liver is potentially the most frequently targeted organ by cosmetic ingredients when orally administered to experimental animals, followed by the kidney and the spleen. Combined listing of altered morphological, histopathological, and biochemical parameters subsequently indicated the possible occurrence of hepatotoxicity, including steatosis and cholestasis, triggered by a limited number of cosmetic compounds. These findings are not only of relevance for the in vitro modeling efforts and choice of compounds to be tested in the SEURAT project cluster, but also demonstrate the importance of using previously generated toxicological data through an electronic databank for addressing specific questions regarding the safety evaluation of cosmetic ingredients.

  8. Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

    2012-08-01

    To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

  9. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

    Directory of Open Access Journals (Sweden)

    Ryu HJ

    2014-12-01

    was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. Keywords: zinc oxide, nanoparticles, subchronic toxicity, dermal exposure

  10. Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M

    2015-09-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

  11. Study of four weeks repeated-dose toxic test of Sweet Bee Venom in rats Original Articles

    Directory of Open Access Journals (Sweden)

    Kwon Hae-Yon

    2011-03-01

    Full Text Available Objectives: This study was performed to analyse four weeks repeated -dose toxicity of Sweet Bee Venom (SBV-pure melittin, the major component of honey bee venom in rats. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLPat Biotoxtech Company, a non-clinical study authorized institution. Male and female rats of 5 weeks old were chosen for the pilot study of four weeks repeated-dose toxicity and was injected at the level of 0.56 mg/kg body weight (eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14 mg/kg as midium and low dosage, respectively. Equal amount of normal saline was injected as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups appealed pain sense in the treating time compared to the control group, and side effects such as hyperemia and movement disorder were observed around the area of injection in all experiment groups, and the higher dosage in treatment, the higher occurrence in side effects. 3. Concerning weight measurement, neither male nor female groups showed significant changes compared to the control group. 4. Concerning to the CBC and biochemistry, all experiment groups didn't show any significant changes compared to the control group. 5. Concerning weight measurement of organs, experiment groups didn't show any significant changes compared to the control group. 6. To verify abnormalities of organs and tissues, those such as cerebellum, cerebrum, liver, lung, kidney,and spinal cords were removed and we conducted histologocal observation with H-E staining.Concerning the histologocal observation of liver tissues, some fatty changes were observed around portal vein in 0.56 mg/kg experiment group. But another organs were not detected in any abnormalities. 7. The proper high dosage of SBV for the thirteen weeks repeated test in rats may be 0.28 mg

  12. Cardiovascular effects, induction and recovery characteristics and alfaxalone dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous anaesthesia in dogs.

    Science.gov (United States)

    Dehuisser, Virginie; Bosmans, Tim; Kitshoff, Adriaan; Duchateau, Luc; de Rooster, Hilde; Polis, Ingeborgh

    2017-11-01

    To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs. Prospective, blinded, randomized, experimental study. A group of 12 intact female dogs. Following intramuscular dexmedetomidine (10 μg kg -1 ) and methadone (0.1 mg kg -1 ) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg -1 ) (group AP) or alfaxalone (2 mg kg -1 ) preceded by fentanyl (2 μg kg -1 ) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg -1 minute -1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 μg kg -1 hour -1 ) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05). The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg -1 minute -1 (group AP) versus 0.13 ± 0.01 mg kg -1 minute -1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups. In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia

  13. Granulomatous interstitial pneumonia in a miniature swine associated with repeated intravenous injections of Tc-99m human serum albumin: concise communication

    International Nuclear Information System (INIS)

    Whinnery, J.E.; Young, J.T.

    1980-01-01

    Albumin lung-scanning agents have a proven high degree of safety, with the only contraindication to their use being allergic hypersensitivity. We have used these agents to investigate the physiologic effects of high G/sub z/ acceleratory forces on pulmonary perfusion using the miniature swine. Multiple doses of human macroaggregated albumin and human-albumin microspheres were given to a miniature swine at various levels of centrifugal acceleration over a 6-wk period. The dosages given were the same per kilogram as those used for routine clinical human studies. The animal subsequently died from a severe granulomatous interstitial pneumonia. The granulomatous lesions suggest that the pathogenesis may have involved a cell-mediated delayed hypersensitivity. This interstitial pneumonia may represent the end point in a chronic hypersensitivity response to the human-albumin lung-scanning agents

  14. Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects.

    Science.gov (United States)

    Munjal, Sagar; Gautam, Anirudh; Okumu, Franklin; McDowell, James; Allenby, Kent

    2016-01-01

    In a randomized, parallel-group, single-center study in 42 healthy adults, the safety and pharmacokinetic parameters of an intravenous formulation of 18.75 and 37.5 mg diclofenac sodium (DFP-08) following single- and multiple-dose bolus administration were compared with diclofenac potassium 50 mg oral tablets. Mean AUC0-inf values for a 50-mg oral tablet and an 18.75-mg intravenous formulation were similar (1308.9 [393.0]) vs 1232.4 [147.6]). As measured by the AUC, DFP-08 18.75 mg and 37.5 mg demonstrated dose proportionality for extent of exposure. One subject in each of the placebo and DFP-08 18.75-mg groups and 2 subjects in the DFP-08 37.5-mg group reported adverse events that were considered by the investigator to be related to the study drug. All were mild in intensity and did not require treatment. Two subjects in the placebo group and 1 subject in the DFP-08 18.75-mg group reported grade 1 thrombophlebitis; no subjects reported higher than grade 1 thrombophlebitis after receiving a single intravenous dose. The 18.75- and 37.5-mg doses of intravenous diclofenac (single and multiple) were well tolerated for 7 days. Additional efficacy and safety studies are required to fully characterize the product. © 2015, The American College of Clinical Pharmacology.

  15. Repeated Intramuscular-dose Toxicity Test of Water-soluble Carthami Flos (WCF Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Yoo-min Choi

    2015-03-01

    Full Text Available Objectives: Water-soluble carthami flos (WCF is a new mixture of Carthami flos (CF pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS. Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.

  16. Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity.

    Science.gov (United States)

    Mancebo, A; Casacó, A; González, B; Ledón, N; Sorlozabal, J; León, A; Gómez, D; González, Y; Bada, A M; González, C; Arteaga, M E; Ramírez, H; Fuentes, D

    2012-05-09

    CIMAvax-EGF consists of a human recombinant epidermal growth factor (EGF), coupled to P64k, a recombinant carrier protein from N. meningitis, and Montanide ISA 51 as adjuvant. The vaccine immunization induces a specific antibody production, inhibiting the EGF/EGF-R interaction through EGF deprivation. The objective of this study was to assess the CIMAvax-EGF toxicity in Sprague Dawley rats after intramuscular administration of repeated doses (6 months) and at the same time to determine if rat is a relevant species for studying CIMAvax-EGF vaccine. Rats were randomly distributed into four groups: control, Montanide ISA 51, treated with 1× and 15× of human total dose of the antigen. Animals were immunized weekly during 9 weeks, plus 9 immunizations every 14 days. Rats were inspected daily for clinical signs. Body weight, food consumption, and rectal temperature were measured during the administration of doses. Blood samples were collected for hematological, serum biochemical determinations and EGF titles at the beginning, three months and at the end of experimentation. Gross necropsy and histological examination of tissues were performed on animals at the end of the assay. Vaccine provoked the apparition of antibodies against EGF in the rats, demonstrating rat species relevance in these studies. Body weight gain, food and water consumption were not affected. CIMAvax-EGF and Montanide ISA 51 produced local damage at the administration site, showing multiple cysts and granulomas. Both vaccine-treated groups showed neutrophil elevation, besides an AST increase probably related to the damage at the administration site. Rectal temperature was found to be significantly higher in 15× treated group after immunizations, probably induced by the inflammatory process at the injection site. In summary, the clinical pathology findings together with the body temperature results, appear to be caused by the inflammatory reaction at the administration site of the vaccine, mainly

  17. Pharmacokinetics of meloxicam after intravenous, intramuscular, and oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Molter, Christine M; Court, Michael H; Cole, Gretchen A; Gagnon, David J; Hazarika, Suwagmani; Paul-Murphy, Joanne R

    2013-03-01

    To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). 11 healthy parrots. Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

  18. Computed tomography versus intravenous urography in diagnosis of acute flank pain from urolithiasis: a randomized study comparing imaging costs and radiation dose

    International Nuclear Information System (INIS)

    Thomson, J.M.Z.; Maling, T.M.J.; Glocer, J.; Mark, S.; Abbott, C.

    2001-01-01

    The equivalent sensitivity of non-contrast computed tomography (NCCT) and intravenous urography (IVU) in the diagnosis of suspected ureteric colic has been established. Approximately 50% of patients with suspected ureteric colic do not have a nephro-urological cause for pain. Because many such patients require further imaging studies, NCCT may obviate the need for these studies and, in so doing, be more cost effective and involve less overall radiation exposure. The present study compares the total imaging cost and radiation dose of NCCT versus IVU in the diagnosis of acute flank pain. Two hundred and twenty-four patients (157 men; mean age 45 years; age range 19-79 years) with suspected renal colic were randomized either to NCCT or IVU. The number of additional diagnostic imaging studies, cost (IVU A$ 136; CTU A$ 173), radiation exposure and imaging times were compared. Of 119(53%) patients with renal obstruction, 105 had no nephro-urological causes of pain. For 21 (20%) of these patients an alternative diagnosis was made at the initial imaging, 10 of which were significant. Of 118 IVU patients, 28 (24%) required 32 additional imaging tests to reach a diagnosis, whereas seven of 106 (6%) NCCT patients required seven additional imaging studies. The average total diagnostic imaging cost for the NCCT group was A$181.94 and A$175.46 for the IVU group (P< 0.43). Mean radiation dose to diagnosis was 5.00 mSv (NCCT) versus 3.50 mSv (IVU) (P < 0.001). Mean imaging time was 30 min (NCCT) versus 75 min (IVU) (P < 0.001). Diagnostic imaging costs were remarkably similar. Although NCCT involves a higher radiation dose than IVU, its advantages of faster diagnosis, the avoidance of additional diagnostic imaging tests and its ability to diagnose other causes makes it the study of choice for acute flank pain at Christchurch Hospital. Copyright (2001) Blackwell Science Pty Ltd

  19. A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.

    Directory of Open Access Journals (Sweden)

    Michelle R Newman

    Full Text Available The low dose radioadaptive response has been shown to be protective against high doses of radiation as well as aging-induced genomic instability. We hypothesised that a single whole-body exposure of low dose radiation would induce a radioadaptive response thereby reducing or abrogating aging-related changes in repeat element DNA methylation in mice. Following sham or 10 mGy X-irradiation, serial peripheral blood sampling was performed and differences in Long Interspersed Nucleic Element 1 (L1, B1 and Intracisternal-A-Particle (IAP repeat element methylation between samples were assessed using high resolution melt analysis of PCR amplicons. By 420 days post-irradiation, neither radiation- or aging-related changes in the methylation of peripheral blood, spleen or liver L1, B1 and IAP elements were observed. Analysis of the spleen and liver tissues of cohorts of untreated aging mice showed that the 17-19 month age group exhibited higher repeat element methylation than younger or older mice, with no overall decline in methylation detected with age. This is the first temporal analysis of the effect of low dose radiation on repeat element methylation in mouse peripheral blood and the first to examine the long term effect of this dose on repeat element methylation in a radiosensitive tissue (spleen and a tissue fundamental to the aging process (liver. Our data indicate that the methylation of murine DNA repeat elements can fluctuate with age, but unlike human studies, do not demonstrate an overall aging-related decline. Furthermore, our results indicate that a low dose of ionising radiation does not induce detectable changes to murine repeat element DNA methylation in the tissues and at the time-points examined in this study. This radiation dose is relevant to human diagnostic radiation exposures and suggests that a dose of 10 mGy X-rays, unlike high dose radiation, does not cause significant short or long term changes to repeat element or global DNA

  20. Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Shin-Ae; Tsolmon, Bilegtsaikhan [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Mann, Aman P. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Zheng, Wei; Zhao, Lichao; Zhao, Yan Daniel [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Volk, David E.; Lokesh, Ganesh L.-R. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Morris, Lynsie; Gupta, Vineet; Razaq, Wajeeha [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Rui, Hallgeir [Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107 (United States); Suh, K. Stephen [John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601 (United States); Gorenstein, David G. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Tanaka, Takemi, E-mail: takemi-tanaka@ouhsc.edu [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States)

    2015-08-15

    The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor.

  1. Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

    International Nuclear Information System (INIS)

    Kang, Shin-Ae; Tsolmon, Bilegtsaikhan; Mann, Aman P.; Zheng, Wei; Zhao, Lichao; Zhao, Yan Daniel; Volk, David E.; Lokesh, Ganesh L.-R.; Morris, Lynsie; Gupta, Vineet; Razaq, Wajeeha; Rui, Hallgeir; Suh, K. Stephen; Gorenstein, David G.; Tanaka, Takemi

    2015-01-01

    The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor

  2. Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans

    Science.gov (United States)

    D'Souza, Deepak Cyril; Fridberg, Daniel J; Skosnik, Patrick D; Williams, Ashley; Roach, Brian; Singh, Nagendra; Carbuto, Michelle; Elander, Jacqueline; Schnakenberg, Ashley; Pittman, Brian; Sewell, R Andrew; Ranganathan, Mohini; Mathalon, Daniel

    2012-01-01

    Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (Δ9-THC) on psychophysiological indices of information processing in humans. Healthy subjects (n=26) completed three test days during which they received intravenous Δ9-THC (placebo, 0.015 and 0.03 mg/kg) in a within-subject, double-blind, randomized, cross-over, and counterbalanced design. Psychophysiological data (electroencephalography) were collected before and after drug administration while subjects engaged in an event-related potential (ERP) task known to be a valid index of attention and cognition (a three-stimulus auditory ‘oddball' P300 task). Δ9-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a. Δ9-THC did not have any effect on the latency of either the P300a or P300b, or on early sensory-evoked ERP components preceding the P300 (the N100). Concomitantly, Δ9-THC induced psychotomimetic effects, perceptual alterations, and subjective ‘high' in a dose-dependent manner. Δ9-THC -induced reductions in P3b amplitude correlated with Δ9-THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to Δ9-THC, there were no dose-related effects of Δ9-THC on P300a/b amplitude between cannabis-free and recent cannabis users. Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, Δ9-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact

  3. Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases

    Directory of Open Access Journals (Sweden)

    Wust Peter

    2010-05-01

    Full Text Available Abstract Background To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice. Methods Twenty patients with liver metastases were treated repeatedly (2 - 4 times at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion, and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy for different α/β values (2, 3, 10, 20, 100 based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D90 as the BED exposing 90% of the pseudolesion in MRI. Results The tolerance doses D90 after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D90 with respect to the intervals between the first irradiation and the MRI control (p 90 and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term. Conclusions Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy. This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD. Repeated small volume irradiation may be applied safely within the limits of this study.

  4. Comparison in the calculation of committed effective dose using the ICRP 30 and ICRP 60 models for a repeated incorporation by inhalation of I-125

    International Nuclear Information System (INIS)

    Carreno P, A.L.; Cortes C, A.; Alonso V, G.; Serrano P, F.

    2005-01-01

    Presently work, a comparison in the calculation of committed effective dose using the models of the ICRP 30 and those of the ICRP 60 for the analysis of internal dose due to repeated incorporation of I-125 is shown. The estimations of incorporated activity are obtained starting from the proportionate data for an exercise of inter comparison, with which it should be determined the internal dose later on. For to estimate the initial activity incorporated by repeated dose was assumed that this it was given through of multiple individual incorporations which happened in the middle points of the monitoring periods. The results using the models of the ICRP 30 and of the ICRP 60 are compared and the causes of the differences are analyzed. (Author)

  5. Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang Bing; Feng Weiyue, E-mail: fengwy@mail.ihep.ac.cn; Zhu Motao; Wang Yun; Wang Meng [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Gu Yiqun [Maternity Hospital of Haidian District (China); Ouyang Hong; Wang Huajian; Li Ming; Zhao Yuliang, E-mail: zhaoyuliang@mail.ihep.ac.cn; Chai Zhifang [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Wang Haifang [Peking University, College of Chemistry and Molecular Engineering (China)

    2009-01-15

    Olfactory tract has been demonstrated to be an important portal for inhaled solid nanoparticle transportation into the central nervous system (CNS). We have previously demonstrated that intranasally instilled Fe{sub 2}O{sub 3} nanoparticles could transport into the CNS via olfactory pathway. In this study, we investigated the neurotoxicity and size effect of repeatedly low-dose (130 {mu}g) intranasal exposure of nano- and submicron-sized Fe{sub 2}O{sub 3} particles (21 nm and 280 nm) to mice. The biomarkers of oxidative stress, activity of nitric oxide synthases and release of monoamine neurotransmitter in the brain were studied. Our results showed that significant oxidative stress was induced by the two sizes of Fe{sub 2}O{sub 3} particles. The activities of GSH-Px, Cu,Zn-SOD, and cNOS significantly elevated and the total GSH and GSH/GSSG ratio significantly decreased in the olfactory bulb and hippocampus after the nano- and submicron-sized Fe{sub 2}O{sub 3} particle treatment (p < 0.05). The nano-sized Fe{sub 2}O{sub 3} generally induced greater alteration and more significant dose-effect response than the submicron-sized particle did. Some slight perturbation of monoamine neurotransmitters were found in the hippocampus after exposure to the two sizes of Fe{sub 2}O{sub 3} particle. The TEM image showed that some ultrastructural alterations in nerve cells, including neurodendron degeneration, membranous structure disruption and lysosome increase in the olfactory bulb, slight dilation in the rough endoplasmic reticulum and lysosome increase in the hippocampus were induced by the nano-sized Fe{sub 2}O{sub 3} treatment. In contrast, in the submicron-sized Fe{sub 2}O{sub 3} treated mice, slightly swollen mitochondria and some vacuoles were observed in the olfactory bulb and hippocampus, respectively. These results indicate that intranasal exposure of Fe{sub 2}O{sub 3} nanoparticles could induce more severe oxidative stress and nerve cell damage in the brain than the

  6. Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans.

    Science.gov (United States)

    Saunders, J P; Donner, T W; Sadler, J H; Levin, G V; Makris, N G

    1999-04-01

    D-tagatose, a stereoisomer of D-fructose, is a naturally occurring ketohexose proposed for use as a low-calorie bulk sweetener. Ingested D-tagatose appears to be poorly absorbed. The absorbed portion is metabolized in the liver by a pathway similar to that of D-fructose. The main purpose of this study was to determine if acute or repeated oral doses of D-tagatose would cause elevations in plasma uric acid (as is seen with fructose) in normal humans and Type 2 diabetics. In addition, effects of subchronic D-tagatose ingestion on fasting plasma phosphorus, magnesium, lipids, and glucose homeostasis were studied. Eight normal subjects and eight subjects with Type 2 diabetes participated in this two-phase study. Each group was comprised of four males and four females. In the first phase, all subjects were given separate 75 g 3-h oral glucose and D-tagatose tolerance tests. Uric acid, phosphorus, and magnesium were determined in blood samples collected from each subject at 0, 30, 60, 120, and 180 min after dose. In the 8-week phase of the study, the normals were randomly placed into two groups which received 75 g of either D-tagatose or sucrose (25 g with each meal) daily for 8 weeks. The diabetics were randomized into two groups which received either 75 g D-tagatose or no supplements of sugar daily for 8 weeks. Uric acid, phosphorus, magnesium, lipids, glycosylated hemoglobin, glucose, and insulin were determined in fasting blood plasma of all subjects at baseline (time zero) and biweekly over the 8 weeks. The 8-week test did not demonstrate an increase in fasting plasma uric acid in response to the daily intake of D-tagatose. However, a transient increase of plasma uric acid levels was observed after single doses of 75 g of D-tagatose in the tolerance test. Plasma uric acid levels were found to rise and peak at 60 min after such dosing. No clinical relevance was attributed to this treatment-related effect because excursions of plasma uric acid levels above the normal

  7. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial.

    Science.gov (United States)

    Beaudoin, Francesca L; Lin, Charlie; Guan, Wentao; Merchant, Roland C

    2014-11-01

    Low-dose ketamine has been used perioperatively for pain control and may be a useful adjunct to intravenous (IV) opioids in the control of acute pain in the emergency department (ED). The aim of this study was to determine the effectiveness of low-dose ketamine as an adjunct to morphine versus standard care with morphine alone for the treatment of acute moderate to severe pain among ED patients. A double-blind, randomized, placebo-controlled trial with three study groups was conducted at a large, urban academic ED over a 10-month period. Eligible patients were 18 to 65 years old with acute moderate to severe pain (score of at least 5 out of 10 on the numerical pain rating scale [NRS] and pain duration ketamine (group 1), or 3) morphine and 0.3 mg/kg ketamine (group 2). Participants were assessed at 30, 60, and 120 minutes after study medication administration and received rescue analgesia as needed to target a 50% reduction in pain. The primary outcome measure of pain relief, or pain intensity reduction, was derived using the NRS and calculated as the summed pain-intensity (SPID) difference over 2 hours. The amount and timing of rescue opioid analgesia was evaluated as a secondary outcome. The occurrence of adverse events was also measured. Sixty patients were enrolled (n = 20 in each group). There were no differences between study groups with respect to age, sex, race/ethnicity, preenrollment analgesia, or baseline NRS. Over the 2-hour poststudy medication administration period, the SPIDs were higher (greater pain relief) for the ketamine study groups than the control group (standard care 4.0, interquartile range [IQR] = 1.8 to 6.5; group 1 7.0, IQR = 4.3 to 10.8; and group 2 7.8, IQR = 4.8 to 12.8; p ketamine groups were similar (p pain intensity up to 2 hours, whereas group 1 was similar to standard care by 2 hours. Similar numbers of patients received rescue analgesia: standard care group, seven of 20, 35%; group 1, four of 20, 20%; and group 2, four of 20, 20

  8. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters

    Directory of Open Access Journals (Sweden)

    Carolina L. Haass-Koffler

    2017-12-01

    Full Text Available The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled “Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers” (Haass-Koffler et al., 2017 [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73. Keywords: Glutamate receptor subtype 5 (mGlu5, Allosteric modulator, GET 73, Safety, Tolerability

  9. Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters.

    Science.gov (United States)

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-12-01

    The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled "Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers" (Haass-Koffler et al., 2017) [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK) parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73.

  10. [Late sequelae of central nervous system prophylaxis in children with acute lymphoblastic leukemia: high doses of intravenous methotrexate versus radiotherapy of the central nervous system--review of literature].

    Science.gov (United States)

    Zając-Spychała, Olga; Wachowiak, Jacek

    2012-01-01

    Acute lymphoblastic leukemia is the most common malignancy in children. All current therapy regimens used in the treatment of childhood acute lymphoblastic leukemia include prophylaxis of the central nervous system. Initially it was thought that the best way of central nervous system prophylaxis is radiotherapy. But despite its effectiveness this method, may cause late sequelae and complications. In the programme currently used in Poland to treat acute lymphoblastic leukemia, prophylactic radiotherapy has been reduced by 50% (12 Gy) and is used only in patients stratified into the high risk group and in patients diagnosed as T-cell ALL (T-ALL). Complementary to radiotherapy, intrathecal methotrexate is given alone or in combination with cytarabine and hydrocortisone is given, as well as systemic chemotherapy with intravenous methotrexate is administered in high or medium doses (depending on risk groups and leukemia immunophenotype). Recent studies have shown that high dose irradiation of the central nervous system impairs cognitive development causing memory loss, visuomotor coordination impairment, attention disorders and reduction in the intelligence quotient. It has been proved that the degree of cognitive impairment depends on the radiation dose directed to the medial temporal lobe structures, particularly in the hippocampus and the surrounding cortex. Also, methotrexate used intravenously in high doses, interferes with the metabolism of folic acid which is necessary for normal development and the optimal functioning of neurons in the central nervous system. It has been proved that patients who have been treated with high doses of methotrexate are characterized by reduced memory skills and a lower intelligence quotient. The literature data concerning long term neuroanatomical abnormalities and neuropsychological deficits are ambiguous, and there is still no data concerning current methods of central nervous system prophylaxis with low doses of irradiation in

  11. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Directory of Open Access Journals (Sweden)

    L John Hoffer

    Full Text Available Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type

  12. Visualization of endolymphatic hydrops in meniere's disease after single-dose intravenous gadolinium-based contrast medium. Timing of optimal enhancement

    International Nuclear Information System (INIS)

    Naganawa, Shinji; Yamazaki, Masahiro; Kawai, Hisashi; Bokura, Kiminori; Sone, Michihiko; Nakashima, Tsutomu

    2012-01-01

    Visualization of endolymphatic hydrops (EH) in patients with Meniere's disease (MD) is now possible by heavily T 2 -weighted 3-dimensional fluid-attenuated inversion recovery (h T 2 W-3D-FLAIR) obtained 4 hours after intravenous (IV) administration of single dose gadolinium-based contrast medium (GBCM). Although maximum enhancement has been reported 4 hours after contrast administration in healthy volunteers, the timing of optimal enhancement in patients with MD is not reported. We investigated if that optimal timing is earlier or later than 4 hours. We evaluated 10 consecutive patients with suspected MD whom we randomly divided into 2 groups. We obtained h T 2 W-3D-FLAIR before GBCM administration and 10 min, 3.5 hours, and 4 hours after GBCM administration in Group A and before and 10 min, 4 hours, and 4.5 hours after GBCM administration in Group B. We compared signal intensity ratio (SIR) values of the perilymph and pons between 3.5 and 4 hours in Group A and between 4 and 4.5 hours in Group B and evaluated grades of EH at 3.5 and 4 hours in Group A and at 4 and 4.5 hours in Group B. SIR values did not differ significantly between 3.5 and 4 hours in Group A and between 4 and 4.5 hours in Group B. However, SIR values at 4 hours were significantly higher in Group A than Group B. Grades of EH agreed between 3.5 and 4 hours in Group A and between 4 and 4.5 hours in Group B. The optimal timing of contrast enhancement in patients with suspected MD remains unclear, but evaluation of EH may be possible from 3.5 to 4.5 hours after contrast administration. (author)

  13. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.

    Science.gov (United States)

    Hoffer, L John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H

    2015-01-01

    Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy

  14. Evaluation of the repeated dose liver micronucleus assay using young adult rats with cyclophosphamide monohydrate: a report of a collaborative study by CSGMT/JEMS.MMS.

    Science.gov (United States)

    Matsumoto, Kazumi; Zaizen, Kazuyo; Miyamoto, Atsushi; Wako, Yumi; Kawasako, Kazufumi; Ishida, Hisao

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect liver carcinogens, and this assay could be integrated into general toxicological studies. In this study, in order to assess the performance of the assay, cyclophosphamide monohydrate (CP) was tested in a 14-day RDLMN assay. Based on the results of the 4-day repeated dose-finding study, 10 mg/kg/day of CP was selected as the highest dose and the lower doses were set at 5, 2.5, 1.25, and 0.625 mg/kg/day for the 14-day RDLMN assay. On the day after the completion of the dosing period, specimens of hepatocytes and bone marrow cells were prepared and the induction of micronuclei was assessed. No changes were observed in the incidences of micronucleated hepatocytes. Nevertheless, the incidences of micronucleated immature erythrocytes in the bone marrow were increased significantly at CP doses of 1.25 mg/kg/day or more. These findings are consistent with reports that CP induces tumors in various tissues but it does not induce liver tumors.

  15. Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

    Science.gov (United States)

    Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

    2018-06-01

    G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Study of a 13-weeks, Repeated, Intramuscular Dose, Toxicity Test of Sweet Bee Venom in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hyunmin Kang

    2014-06-01

    Full Text Available Objectives:This study was performed to analyze a 13-week repeated dose toxicity test of Sweet Bee Venom (SBV extracted from bee venom and administered in Sprague-Dawley (SD rats. Methods:Male and female 5-week-old SD rats were treated once daily with SBV (high-dosage group: 0.28 mg/kg; medium-dosage group: 0.14 mg/kg; or low-dosage group: 0.07 mg/kg for 13 weeks. Normal saline was administered to the control group in a similar manner (0.2 mL/kg. We conducted clinical observations, body weight measurements, ophthalmic examinations, urinalyses, hematology and biochemistry tests, and histological observations using hematoxylin and eosin (H&E staining to identify any abnormalities caused by the SBV treatment. Results:During this study, no mortality was observed in any of the experimental groups. Hyperemia and a movement disorder were observed around the area of in all groups that received SBV treatment, with a higher occurrence in rats treated with a higher dosage. Male rats receiving in the high-dosage group showed a significant decrease in weight during the treatment period. Compared to the control group, no significant changes in the ophthalmic parameters, the urine analyses, the complete blood cell count (CBC, and the biochemistry in the groups treated with SBV. Compared to the control group, some changes in organ weights were observed in the medium-and the high-dosage groups, but the low-dosage group showed no significant changes. Histological examination of thigh muscle indicated cell infiltration, inflammation, degeneration, and necrosis of muscle fiber, as well as fibrosis, in both the medium- and the high-dosage groups. Fatty liver change was observed in the periportal area of rats receiving medium and high dosages of SBV. No other organ abnormalities were observed. Conclusion:Our findings suggest that the No Observed Adverse Effect Level (NOAEL of SBV is approximately 0.07 mg/kg in male and female SD rats.

  17. Single-dose intravenous iron infusion versus red blood cell transfusion for the treatment of severe postpartum anaemia: a randomized controlled pilot study.

    Science.gov (United States)

    Holm, C; Thomsen, L L; Norgaard, A; Langhoff-Roos, J

    2017-02-01

    There are no randomized trials comparing intravenous iron to RBC transfusion for the treatment of severe postpartum anaemia. The objectives of this study were to evaluate the feasibility of randomizing women with severe postpartum anaemia secondary to postpartum haemorrhage to RBC transfusion or intravenous iron, and to describe patient-reported outcomes, and haematological and iron parameters. Women with a postpartum haemorrhage exceeding 1000 ml and an Hb between 5·6 and 8·1 g/dl were randomized to 1500 mg of intravenous iron (n = 7) isomaltoside or RBC transfusion (n = 6). Participants completed the Multidimensional Fatigue Inventory and Edinburgh Postnatal Depression Scale, and blood samples were drawn at inclusion, daily during the first week and at weeks 3, 8 and 12. We screened 162 women and included 13 (8%). There was no significant difference between groups in fatigue or depression scores. RBC transfusion was associated with a higher Hb on day 1, inhibition of reticulocytosis during the first week and low iron levels. Intravenous iron was associated with increased reticulocytosis during the first week, repleted iron stores and a higher Hb in weeks 3-12. This pilot study shows that intravenous iron could be an attractive alternative to RBC transfusion in severe postpartum anaemia, and that a larger trial is needed and feasible. © 2016 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

  18. Repeated irradiations with γ-rays at a dose of 0.5 Gy may exacerbate asthma

    International Nuclear Information System (INIS)

    Fang, Su-ping; Tago, Fumitoshi; Tanaka, Takashi; Simura, Noriko; Kojima, Shuji; Muto, Yasuko; Goto, Resuke

    2005-01-01

    We previously showed that 0.5 Gy whole-body γ-ray irradiation with a single or small number of repeated exposures inhibits tumor growth in mice, via elevation of the IFNγ/IL-4 ratio concomitantly with a decrease in the percentage of B cells. Here we examined whether repeated 0.5 Gy γ-rays irradiation can improve asthma in an ovalbumin (OVA)-induced asthmatic mouse model. We found that repeated irradiation (10 times) with 0.5 Gy of γ-rays significantly increased total IgE in comparison with the disease-control group. The levels of IL-4 and IL-5 were also significantly higher in the γ-ray-irradiated group, while that of IFN-γ was significantly lower, resulting in a further decrease of the IFN-γ/IL-4 ratio from the normal value. These results indicate that the repeated irradiation with γ-rays may exacerbate asthma, and may have opposite effects on different immune reactions unlike the irradiation with a single or small number of repeated exposures. (author)

  19. Evaluation of repeated dose micronucleus assays of the liver using N-nitrosopyrrolidine: a report of the collaborative study by CSGMT/JEMS.MMS.

    Science.gov (United States)

    Ogawa, Izumi; Hagioa, Soichiro; Furukawa, Satoshi; Abe, Masayoshi; Kuroda, Yusuke; Hayashi, Seigo; Wako, Yumi; Kawasako, Kazufumi

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay has the potential to detect liver carcinogens, and can be integrated into a general toxicological study. To assess the performance of the assay, N-nitrosopyrrolidine (NPYR), a genotoxic hepatocarcinogen, was tested in 14- or 28-day RDLMN assays. NPYR was orally administered to rats at a daily dose of 25, 50 or 100 mg/kg. One day after the last administration, a portion of the liver was removed and hepatocyte micronucleus (MN) specimens were prepared by the new method recently established by Narumi et al. In addition, a bone marrow MN assay and a histopathological examination of the liver were conducted. The detection of Phospho-Histone H3 was performed by immunohistochemistry to evaluate the proliferation rate of hepatocytes. The results showed significant increase in the number of micronucleated hepatocytes and Phospho-Histone H3-positive cells from the lowest dose in both 14- and 28-day RDLMN assays. On the other hand, the bone marrow MN assay yielded a negative result, which was in accordance with the existing report of the bone marrow MN assay using mice. Upon histopathological examination, inflammatory lesions and hypertrophy were noted, which may explain the increase in the hepatocyte proliferation and the enhancement of MN induction by NPYR. Our findings indicate that the RDLMN assay could be a useful tool for comprehensive risk assessment of carcinogenicity by providing information on both genotoxicity and histopathology when integrated into a general repeat dosing toxicity assay.

  20. Analgesia induced by repeated exposure to low dose X-rays in mice, and involvement of the accessory olfactory system in modulation of the radiation effects

    International Nuclear Information System (INIS)

    Miyachi, Yukihisa; Yamada, Takeshi

    1997-01-01

    The effects of low-dose X-rays on mouse nociceptive behavior were examined using a formalin injected test which rated the amount of time the animals spent licking the injected hind-paw. Male ICR White Swiss mice showed a marked suppression of licking behavior after repeated low-dose X-irradiation (5 cGy/day, 6 consecutive days). The most profound effect was observed on the day 30 after irradiation. The decline of licking behavior, however, was not observed at all following olfactory bulbectomy or vomeronasal tract cut. The analgesic effects could be observed in writhing animals administered acetic-acid intraperitoneally. Moreover, analgesia was totally blocked by the administration of N-nitro-L-arginine, a nitric oxide synthase inhibitor, to accessory olfactory bulbs prior to the exposure. The present results indicate that the olfactory system plays an important role in modulation of radiation-induced analgesia, and a possible involvement of nitric oxide in the formation of recognition memory subjected to repeated X-rays. Relatively higher doses (5 cGy x 9 days, 5 cGy x 12 days), however, did not induce such effects, namely, the decline of nociceptive response was limited to the animals irradiated with the smaller dose. (author)

  1. Interactions between cannabidiol and Δ9-THC following acute and repeated dosing: Rebound hyperactivity, sensorimotor gating and epigenetic and neuroadaptive changes in the mesolimbic pathway.

    Science.gov (United States)

    Todd, Stephanie M; Zhou, Cilla; Clarke, David J; Chohan, Tariq W; Bahceci, Dilara; Arnold, Jonathon C

    2017-02-01

    The evidence base for the use of medical cannabis preparations containing specific ratios of cannabidiol (CBD) and Δ 9 -tetrahydrocannabinol (THC) is limited. While there is abundant data on acute interactions between CBD and THC, few studies have assessed the impact of their repeated co-administration. We previously reported that CBD inhibited or potentiated the acute effects of THC dependent on the measure being examined at a 1:1 CBD:THC dose ratio. Further, CBD decreased THC effects on brain regions involved in memory, anxiety and body temperature regulation. Here we extend on these finding by examining over 15 days of treatment whether CBD modulated the repeated effects of THC on behaviour and neuroadaption markers in the mesolimbic dopamine pathway. After acute locomotor suppression, repeated THC caused rebound locomotor hyperactivity that was modestly inhibited by CBD. CBD also slightly reduced the acute effects of THC on sensorimotor gating. These subtle effects were found at a 1:1 CBD:THC dose ratio but were not accentuated by a 5:1 dose ratio. CBD did not alter the trajectory of enduring THC-induced anxiety nor tolerance to the pharmacological effects of THC. There was no evidence of CBD potentiating the behavioural effects of THC. However we demonstrated for the first time that repeated co-administration of CBD and THC increased histone 3 acetylation (H3K9/14ac) in the VTA and ΔFosB expression in the nucleus accumbens. These changes suggest that while CBD may have protective effects acutely, its long-term molecular actions on the brain are more complex and may be supradditive. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  2. Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration.

    Science.gov (United States)

    Berkó, Szilvia; Szűcs, Kálmán F; Balázs, Boglárka; Csányi, Erzsébet; Varju, Gábor; Sztojkov-Ivanov, Anita; Budai-Szűcs, Mária; Bóta, Judit; Gáspár, Róbert

    2016-01-01

    Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Both intravenously and EP-administered neostigmine (0.2-66.7 μg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 μg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice.

  3. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Shefner, Jeremy M; Watson, Mary Lou; Meng, Lisa; Wolff, Andrew A

    2013-12-01

    Abstract Tirasemtiv is a fast skeletal muscle activator that increases the sensitivity of the sarcomere to calcium, increasing the efficiency of muscle contraction when the muscle is stimulated at submaximal contraction frequencies. A previous study showed single doses of tirasemtiv to be well tolerated and associated with potentially important improvements in a variety of functional outcomes. This study determined safety of tirasemtiv when given at doses up to 500 mg daily for three weeks. Tirasemtiv was given as a single daily dose up to 375 mg for two weeks, with and without concomitant riluzole. In a separate cohort, an ascending dose protocol evaluated a total dose of 500 mg daily given in two divided doses. Safety and tolerability were assessed, as well as measures of function, muscle strength and endurance. Results showed that tirasemtiv was well tolerated, with dizziness the most common adverse event. Tirasemtiv approximately doubled the serum concentration of riluzole. Trends were noted for improvement in ALSFRS-R, Maximum Minute Ventilation, and Nasal Inspiratory Pressure. In conclusion, tirasemtiv is well tolerated and can be given safely with a reduced dose of riluzole. Positive trends in multiple exploratory outcome measures support the further study of this agent in ALS.

  4. Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 22). Effects of 2- and 4-week administration of theobromine on the testis.

    Science.gov (United States)

    Funabashi, H; Fujioka, M; Kohchi, M; Tateishi, Y; Matsuoka, N

    2000-10-01

    The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.

  5. Study on a 4-Week Recovery Test of Sweet Bee Venom after a 13-Week, Repeated, Intramuscular Dose Toxicity Test in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Chungsan Lim

    2014-06-01

    Full Text Available Objectives:This study was performed to check for reversibility in the changes induced by a 13-week, repeated, dose toxicity test of Sweet Bee Venom (SBV in Sprague-Dawley (SD rats. Methods:Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results:(1 Hyperemia and movement disorder were observed in the 13-week, repeated, dose toxicity test, but these symptoms were not observed during the recovery period. (2 The rats in the high-dose group showed no significant changes in weight compared to the control group. (3 No significant differences in the ophthalmic parameters, urine analyses, complete blood cell counts (CBCs, and biochemistry were observed among the recovery groups. (4 No changes in organ weights were observed during the recovery period. (5 Histological examination of the thigh muscle indicated cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis during the treatment period, but these changes were not observed during the recovery period. The fatty liver change that was observed during the toxicity test was not observed during the recovery period. No other organ abnormalities were observed. Conclusion:The changes that occurred during the 13-week, repeated, dose toxicity test are reversible, and SBV can be safely used as a treatment modality.

  6. Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats

    Directory of Open Access Journals (Sweden)

    S.J. Borghoff

    Full Text Available Tetrabromobisphenol A (TBBPA, a nongenotoxic flame retardant, causes uterine tumors in female rats. A proposed mode of action (MoA for these tumors involves an increase in the bioavailability of estradiol as a result of TBBPA inhibiting estrogen sulfotransferases (ES, the enzymes responsible for inactivating and enhancing the elimination of estradiol. The objective of this study was to evaluate the effect of dose and repeated administration of TBBPA on the level of TBBPA, TBBPA-glucuronide (GA and TBBPA-sulfate (S conjugates in plasma, liver and uterus of female Wistar Han rats administered TBBPA (50, 100, 250, 500 or 1000 mg/kg for 28 consecutive days. In accordance with this objective, TBBPA sulfation was used as a surrogate for evaluating the potential for estradiol sulfation to be limited at high dose levels of TBBPA. Blood samples were collected at 4 and 8 h post-dosing on study day 7, 14, and 28, while liver and uterus were collected at the same time points following 28 days of dosing. Tissue samples were analyzed for TBBPA, TBBPA-GA and TBBPA-S by LC–MS/MS. A dose-related increase in the concentration of all three analytes occurred in plasma (day 7, 14, and 28 as well as liver and uterus tissue (day 28 at both 4 and 8 h post dose. The plasma concentration of TBBPA-GA and TBBPA-S was higher in animals dosed for 28 days compared to those dosed for 7 or 14 days showing an increase in systemic circulation of these conjugates with repeated administration. The balance of these conjugates was also different in tissues with TBBPA-S > TBBPA-GA at high doses in the liver and TBBPA-GA > TBBPA-S in both plasma and uterus. In all three tissues the ratio of TBBPA-S/TBBPA-GA showed a decreasing trend with dose, suggesting that at high TBBPA dose levels sulfation of TBBPA becomes limited. This effect was most apparent in the liver and plasma at 28 days of administration. Together these data show that administration of high doses of TBBPA

  7. Low-dose metformin improves pregnancy rate in in vitro fertilization repeaters without polycystic ovary syndrome: prediction of effectiveness by multiple parameters related to insulin resistance.

    Science.gov (United States)

    Jinno, Masao; Kondou, Kenichi; Teruya, Koji

    2010-01-01

    Insulin resistance is associated with aging and stress, both common among patients repeatedly failing to conceive with in vitro fertilization (IVF repeaters). In the present study we examined whether low-dose metformin could improve the outcome in IVF repeaters without polycystic ovary syndrome (PCOS). Study I was a preliminary clinical trial aiming at defining indications for therapy; study II was a prospective randomized study. The studies involved a university hospital and a private infertility clinic. We studied 232 women without PCOS who had failed at least twice to conceive by previous IVF. Metformin (500 mg/ day) was administered for 8 to 12 weeks before and during ovarian stimulation (metformin IVF). In study I, IVF outcomes with metformin (n = 33) were compared to outcomes without metformin of previous IVF in the same subjects. A discriminant score (DS) was determined from nine parameters assessed before metformin administration to predict achievement of ongoing pregnancy by metformin IVF. In study II (n = 199), ongoing pregnancy rates were compared prospectively between groups with/without metformin and with DS above/below 0.6647. Study I. Ongoing pregnancy rate improved significantly with metformin compared with previous IVF, and pregnancy correlated significantly with a DS at an optimal threshold of 0.6647 (sensitivity, 0.90; specificity, 0.91). Study II. Ongoing pregnancy and implantation rates were significantly higher in women with a DS above 0.6647 who received metformin (56% and 33%) compared with those having a DS below 0.6647 with metformin (14% and 11%) and those having a DS above/below 0.6647 without metformin (20% and 7.1%/15% and 11%, respectively). Low-dose metformin improved pregnancy rate in IVF repeaters without PCOS, probably by decreasing insulin resistance. Indication can be determined from insulin-resistance-related multiple parameters assessed before metformin administration.

  8. Needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer evaluated by repeated MRI.

    Science.gov (United States)

    Buus, Simon; Lizondo, Maria; Hokland, Steffen; Rylander, Susanne; Pedersen, Erik M; Tanderup, Kari; Bentzen, Lise

    To quantify needle migration and dosimetric impact in high-dose-rate brachytherapy for prostate cancer and propose a threshold for needle migration. Twenty-four high-risk prostate cancer patients treated with an HDR boost of 2 × 8.5 Gy were included. Patients received an MRI for planning (MRI1), before (MRI2), and after treatment (MRI3). Time from needle insertion to MRI3 was ∼3 hours. Needle migration was evaluated from coregistered images: MRI1-MRI2 and MRI1-MRI3. Dose volume histogram parameters from the treatment plan based on MRI1 were related to parameters based on needle positions in MRI2 or MRI3. Regression was used to model the average needle migration per implant and change in D90 clinical target volume, CTV prostate+3mm . The model fit was used for estimating the dosimetric impact in equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy. Needle migration was on average 2.2 ± 1.8 mm SD from MRI1-MRI2 and 5.0 ± 3.0 mm SD from MRI1-MRI3. D90 CTV prostate+3mm was robust toward average needle migration ≤3 mm, whereas for migration >3 mm D90 decreased by 4.5% per mm. A 3 mm of needle migration resulted in a decrease of 0.9, 1.7, 2.3, 4.8, and 7.6 equivalent dose in 2 Gy fractions for dose levels of 6, 8.5, 10, 15, and 19 Gy, respectively. Substantial needle migration in high-dose-rate brachytherapy occurs frequently in 1-3 hours following needle insertion. A 3-mm threshold of needle migration is proposed, but 2 mm may be considered for dose levels ≥15 Gy. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  9. Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

    Science.gov (United States)

    Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

    2015-04-01

    Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

  10. Effects of annealing on the sensitivity of LiF TLD-100 after repeated use for low dose measurements

    International Nuclear Information System (INIS)

    Ogunleye, O.T.; Richmond, R.G.

    1987-01-01

    The changes in sensitivity of LiF TLD-100 extruded ribbons subjected to repeated use up to 100 times were investigated. Three different annealing regimes were compared. The dosemeters were annealed at 400 0 C followed by (i) a slow or (ii) fast cooling to room temperature or (iii) utilising a 20 s readout process in the reader without a high temperature annealing at 400 0 C. Each of the three groups consisted of two sets of 20 chips each, with one set receiving 500 μ Gy of 90 Sr beta radiation and the other unirradiated. Sensitivity evaluations were performed every five cycles through the first 50 cycles, and on each tenth cycle thereafter. On the average, the fast cooled group maintained their integrity best, while a maximum variation in sensitivity of about 15% was observed in the irradiated set of the slowly cooled group. A permanent increase in sensitivity of at least 10% was observed for the set of dosemeters receiving radiation without annealing. Glow curve analyses showed an increase in the ratio of peaks 4 and 5 with repeated use of this group. (author)

  11. Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid; Langhoff-Roos, Jens

    2015-01-14

    Postpartum haemorrhage can lead to iron deficiency with and without anaemia, the clinical consequences of which include physical fatigue. Although oral iron is the standard treatment, it is often associated with gastrointestinal side effects and poor compliance. To date, no published randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside 1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard medical care. Healthy parturients with a singleton pregnancy will be included within 48 hours after delivery.Participants will complete structured questionnaires that focus on several dimensions of fatigue and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal Depression Scale and the Postpartum Questionnaire), at inclusion and at follow-up visits after three days, one week, three weeks, eight weeks, and 12 weeks postpartum. The primary endpoint is the aggregated change in physical fatigue score within 12 weeks postpartum, as measured by a subscale of the Multidimensional Fatigue Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant difference between the mean scores at 1.8, and the assumed standard deviation at 4.2. Hence, 87 participants per treatment group are needed in order to demonstrate superiority; to provide an extra margin

  12. Prediction of response to continuous irradiation at low dose rate for repeated administrations in radiotherapy with beta emitters

    International Nuclear Information System (INIS)

    Calderon, Carlos; Gonzalez, Joaquin; Quesada, Waldo

    2009-01-01

    The absorbed dose to tumors after systemic administration of radiopharmaceuticals is not sufficient to achieve acceptable levels of probability of tumor control without compromising on critical tissue toxicity (kidney and / or bone marrow (BM)). There are reports of trials with multiple administrations, about tolerance level inter-administration intervals to allow recovery of the BM, with good results. The biokinetic behavior of some radiopharmaceuticals known makes possible the application of several administrations with short intervals of time.It is the present work combines two kinetic models of tumor growth and cell kinetics in the BM for predicting the response to continuous irradiation at low dose rate. The estimation of the effects of irradiation on tumor and kidneys was done using a formulation of the linear-quadratic model functions suitable for dose rate and multi-exponential repair. The estimation of the response in WB performed using a compartmental model previously reported. The absorbed dose to organs were calculated using the MIRD formulation taking into account the effect of irradiation cross. Biokinetic data were used for therapeutic radiopharmaceuticals 90Y, 131I and 177Lu, as well as radiobiological parameters reported for experimental animals. The effect on the response by the variation of inter-administration interval in slow-growing tumors and fast, so as the radiosensitive and radioresistant tumors. You can set conditions irradiation to an acceptable level of thrombocytopenia (onset and duration of the minimum in the curve) and renal irradiation below the limit of tolerance. It is possible to design experiments evaluation of therapeutic radiopharmaceuticals with a greater degree of refinement. (author)

  13. Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hussin Muhammad

    2012-04-01

    Full Text Available Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  14. Evaluation of repeated dose micronucleus assays of the liver and gastrointestinal tract using potassium bromate: a report of the collaborative study by CSGMT/JEMS.MMS.

    Science.gov (United States)

    Okada, Emiko; Fujiishi, Yohei; Narumi, Kazunori; Kado, Shoichi; Wako, Yumi; Kawasako, Kazufumi; Kaneko, Kimiyuki; Ohyama, Wakako

    2015-03-01

    The food additive potassium bromate (KBrO3) is known as a renal carcinogen and causes chromosomal aberrations in vitro without metabolic activation and in vivo in hematopoietic and renal cells. As a part of a collaborative study by the Mammalian Mutagenicity Study group, which is a subgroup of the Japanese Environmental Mutagen Society, we administered KBrO3 to rats orally for 4, 14, and 28 days and examined the micronucleated (MNed) cell frequency in the liver, glandular stomach, colon, and bone marrow to confirm whether the genotoxic carcinogen targeting other than liver and gastrointestinal (GI) tract was detected by the repeated dose liver and GI tract micronucleus (MN) assays. In our study, animals treated with KBrO3 showed some signs of toxicity in the kidney and/or stomach. KBrO3 did not increase the frequency of MNed cells in the liver and colon in any of the repeated dose studies. However, KBrO3 increased the frequency of MNed cells in the glandular stomach and bone marrow. Additionally, the MNed cell frequency in the glandular stomach was not significantly affected by the difference in the length of the administration period. These results suggest that performing the MN assay using the glandular stomach, which is the first tissue to contact agents after oral ingestion, is useful for evaluating the genotoxic potential of chemicals and that the glandular stomach MN assay could be integrated into general toxicity studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a single ascending dose study in opioid-naïve healthy volunteers.

    Science.gov (United States)

    Rauck, Richard; Oh, D Alexander; Parikh, Neha; Koch, Christian; Singla, Neil; Yu, Jin; Nalamachu, Srinivas; Vetticaden, Santosh

    2017-11-01

    Fentanyl sublingual spray offers rapid pain relief in opioid-tolerant cancer patients, and may be useful in acute or post-operative pain. Both opioid-naïve and non-tolerant patients are likely to receive opioids in these settings. Understanding the relationship between systemic exposure of fentanyl sublingual spray and effects on respiratory function in opioid-naïve or non-tolerant populations is important to ensure patient safety. This study evaluated single-dose fentanyl sublingual spray in opioid-naïve participants. Participants were randomized to receive single-dose fentanyl sublingual spray (100, 200, 400, 600, 800 mcg) or fentanyl citrate IV in one of five cohorts. Dosing occurred following a 10-h fast, with fasting continuing for 4 h post-dose. Dose proportionality was assessed using analysis of variance and linear regression techniques. PK assessments and safety monitoring were performed through 24 h post-dose. Safety assessments, including adverse event (AE) monitoring, occurred from dosing through Day 7. Fifty participants (19-53 years) received fentanyl sublingual spray or fentanyl citrate IV. Mean maximum plasma concentrations were reached between 0.27-0.60 h post-dose for fentanyl sublingual spray. Peak (C max ) and total (AUC 0- t , AUC 0-∞ ) fentanyl exposures increased in a linear, but more than dose-proportional manner, with higher doses. The most common AEs were somnolence, nausea, and vomiting. All AEs were mild or moderate in severity. Doses at 400, 600, and 800 mcg were associated with nausea and vomiting, requiring pharmacologic intervention. Hypoxia episodes requiring nasal cannula oxygenation were observed with 600mcg and 800mcg doses. Overall, single-dose fentanyl sublingual spray (100-800 mcg) was generally well tolerated, with greater incidences of AEs (e.g. nausea, vomiting, hypoxia) at higher doses. Doses up to 200 mcg may be safely administered to healthy opioid-naïve individuals with routine monitoring; doses

  16. Disposition of diiosononyl phthalate and its effects on sexual development of the male fetus following repeated dosing in pregnant rats.

    Science.gov (United States)

    Clewell, Rebecca A; Sochaski, Mark; Edwards, Kendra; Creasy, Dianne M; Willson, Gabrielle; Andersen, Melvin E

    2013-01-01

    Pregnant Sprague-Dawley rats received 50, 250, and 500 mg/kg/day diisononyl phthalate (DiNP) from GD 12 to 19 via corn oil gavage to study the dose response for effects on fetal male rat sexual development as well as metabolite disposition in the dam and fetus. Monoisononyl phthalate (MiNP), mono(carboxy-isooctyl) phthalate (MCiOP), mono(hydroxyl-isononyl) phthalate (MHiNP), mono(oxo-isononyl) phthalate (MOiNP), and monoisononyl phthalate glucuronide (MiNP-G) were found in all measured tissues. MCiOP was the major metabolite, followed in decreasing order by MiNP, MHiNP, MOiNP, and MiNP-G. Percentage of dose absorbed decreased at 750 mg/kg/day. Testosterone concentration in the fetal testes was reduced at 250 and 750 mg/kg/day. Multinucleated germ cells were increased in the testes of rats at 250 and 750 mg/kg/day. The no observed effect level (NOEL) for this study was 50 mg/kg/day based on increased MNGs and reduced testes testosterone concentration in the fetal rat. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

    International Nuclear Information System (INIS)

    Churchill, L.; Pazdernik, T.L.; Jackson, J.L.; Nelson, S.R.; Samson, F.E.; McDonough, J.H. Jr.

    1984-01-01

    [3H]Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration

  18. Topographical distribution of decrements and recovery in muscarinic receptors from rat brains repeatedly exposed to sublethal doses of soman

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, L.; Pazdernik, T.L.; Jackson, J.L.; Nelson, S.R.; Samson, F.E.; McDonough, J.H. Jr.

    1984-08-01

    (3H)Quinuclidinyl benzilate binding to rat brain muscarinic receptors decreased after repeated exposure to soman, a potent organophosphorus cholinesterase inhibitor. The topographical distribution of this decrement was analyzed by quantitative receptor autoradiography. After 4 weeks of soman, three times a week, quinuclidinyl benzilate binding decreased to 67 to 80% of control in frontal and parietal cortex, caudate-putamen, lateral septum, hippocampal body, dentate gyrus, superior colliculus, nucleus of the fifth nerve, and central grey. Minor or no decreases were observed in thalamic or hypothalamic nuclei, reticular formation, pontine nuclei, inferior colliculus, nucleus of the seventh nerve, and cerebellum. Scatchard analyses of saturation curves using frontal cortex sections from soman-treated rats revealed a decrease in maximal quinuclidinyl benzilate binding from that in control rats and a return toward control levels by 24 days without any significant change in affinity. These brain areas showing significant decrements in muscarinic receptors recovered with a similar time course. An estimate of the time for 50% recovery for some of the brain areas was 14 days for superior colliculus, 16 days for cortex, and 19 days for hippocampal body. The application of quantitative receptor autoradiography to analyze receptor alterations has been valuable in localizing the telencephalon as a region more susceptible to change in receptor concentration.

  19. Synthetic food coloring and behavior: a dose response effect in a double-blind, placebo-controlled, repeated-measures study.

    Science.gov (United States)

    Rowe, K S; Rowe, K J

    1994-11-01

    To establish whether there is an association between the ingestion of synthetic food colorings and behavioral change in children referred for assessment of "hyperactivity." From approximately 800 children referred to the Royal Children's Hospital (Melbourne) for assessment of suspected hyperactivity, 200 were included in a 6-week open trial of a diet free of synthetic food coloring. The parents of 150 children reported behavioral improvement with the diet, and deterioration on the introduction of foods noted to contain synthetic coloring. A 30-item behavioral rating inventory was devised from an examination of the clinical histories of 50 suspected reactors. Thirty-four other children (23 suspected reactors, 11 uncertain reactors) and 20 control subjects, aged 2 to 14 years, were studied. A 21-day, double-blind, placebo-controlled, repeated-measures study used each child as his or her own control. Placebo, or one of six dose levels of tartrazine (1, 2, 5, 10, 20, 50 mg), was administered randomly each morning, and behavioral ratings were recorded by parents at the end of each 24 hours. The study identified 24 children as clear reactors (19 of 23 "suspected reactors," 3 of 11 "uncertain reactors," and 2 of 20 "control subjects"). They were irritable and restless and had sleep disturbance. Significant reactions were observed at all six dose levels. A dose response effect was obtained. With a dose increase greater than 10 mg, the duration of effect was prolonged. Behavioral changes in irritability, restlessness, and sleep disturbance are associated with the ingestion of tartrazine in some children. A dose response effect was observed.

  20. Safety and PK/PD correlation of TV-1106, a recombinant fused human albumin-growth hormone, following repeat dose administration to monkeys.

    Science.gov (United States)

    Ashkenazi, Nurit; Rosenstock, Moti; Hallak, Hussein; Bassan, Merav; Rasamoelisolo, Michele; Leuschner, Jost; Shinar, Doron

    TV-1106 is a recombinant human albumin genetically fused to growth hormone which is intended to reduce the frequency of injections for GH therapy users. We report the safety, tolerability, pharmacokinetics and pharmacodynamics of repeated subcutaneous injections of TV-1106 in Cynomolgus monkeys. Cynomolgus monkeys received four weekly subcutaneous injections of 0, 5, 10 or 20mg/kg TV-1106 and were monitored for safety signals throughout the study. Serum levels of TV-1106 and insulin-like growth factor 1 (IGF-1) were assayed. Treated animals showed no adverse effects or histopathological changes. TV-1106 serum concentrations showed sustained exposure to the drug. Exposure increased in a dose-dependent manner with peak concentrations at approximately 24h post-dosing and elimination half-lives in the range of 12 to 24h. IGF-1 serum concentrations were elevated throughout the entire study duration, indicative of the pharmacological response. There was a clear correlation between change in IGF-1 levels and dose or exposure to TV-1106. The safety, pharmacokinetic and pharmacodynamic findings support the further development of TV-1106 as a once-weekly administered treatment for patients with GHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Randomized comparative study of intravenous infusion of three different fixed doses of milrinone in pediatric patients with pulmonary hypertension undergoing open heart surgery.

    Science.gov (United States)

    Barnwal, Neeraj Kumar; Umbarkar, Sanjeeta Rajendra; Sarkar, Manjula Sudeep; Dias, Raylene J

    2017-01-01

    Pulmonary hypertension secondary to congenital heart disease is a common problem in pediatric patients presenting for open heart surgery. Milrinone has been shown to reduce pulmonary vascular resistance and pulmonary artery pressure in pediatric patients and neonates postcardiac surgery. We aimed to evaluate the postoperative outcome in such patients with three different fixed maintenance doses of milrinone. Patients were randomized into three groups. All patients received fixed bolus dose of milrinone 50 μg/kg on pump during rewarming. Following this, patients in low-dose group received infusion of milrinone at the rate of 0.375 μg/kg/min, medium-dose group received 0.5 μg/kg/min, and high-dose group received 0.75 μg/kg/min over 24 h. Heart rate, mean arterial pressure (MAP), mean airway pressure (MaP), oxygenation index (OI), and central venous pressure (CVP) were compared at baseline and 24 h postoperatively. Dose of inotropic requirement, duration of ventilatory support and Intensive Care Unit (ICU) stay were noted. MAP, MaP, OI, and CVP were comparable in all three groups postoperatively. All patients in the low-dose group required low inotropic support while 70% of patients in the high-dose group needed high inotropic support to manage episodes of hypotension (P = 0.000). Duration of ventilatory support and ICU stay in all three groups was comparable (P = 0.412, P = 0.165). Low-dose infusions while having a clinical impact were more beneficial in avoiding adverse events and decreasing inotropic requirement without affecting duration of ventilatory support and duration of ICU stay.

  2. Randomized comparative study of intravenous infusion of three different fixed doses of milrinone in pediatric patients with pulmonary hypertension undergoing open heart surgery

    Directory of Open Access Journals (Sweden)

    Neeraj Kumar Barnwal

    2017-01-01

    Full Text Available Background: Pulmonary hypertension secondary to congenital heart disease is a common problem in pediatric patients presenting for open heart surgery. Milrinone has been shown to reduce pulmonary vascular resistance and pulmonary artery pressure in pediatric patients and neonates postcardiac surgery. We aimed to evaluate the postoperative outcome in such patients with three different fixed maintenance doses of milrinone. Methodology: Patients were randomized into three groups. All patients received fixed bolus dose of milrinone 50 μg/kg on pump during rewarming. Following this, patients in low-dose group received infusion of milrinone at the rate of 0.375 μg/kg/min, medium-dose group received 0.5 μg/kg/min, and high-dose group received 0.75 μg/kg/min over 24 h. Heart rate, mean arterial pressure (MAP, mean airway pressure (MaP, oxygenation index (OI, and central venous pressure (CVP were compared at baseline and 24 h postoperatively. Dose of inotropic requirement, duration of ventilatory support and Intensive Care Unit (ICU stay were noted. Results: MAP, MaP, OI, and CVP were comparable in all three groups postoperatively. All patients in the low-dose group required low inotropic support while 70% of patients in the high-dose group needed high inotropic support to manage episodes of hypotension (P = 0.000. Duration of ventilatory support and ICU stay in all three groups was comparable (P = 0.412, P = 0.165. Conclusion: Low-dose infusions while having a clinical impact were more beneficial in avoiding adverse events and decreasing inotropic requirement without affecting duration of ventilatory support and duration of ICU stay.

  3. A 90-day repeated-dose toxicity study of dietary alpha linolenic acid-enriched diacylglycerol oil in rats.

    Science.gov (United States)

    Bushita, Hiroto; Ito, Yuichi; Saito, Tetsuji; Nukada, Yuko; Ikeda, Naohiro; Nakagiri, Hideaki; Saito, Kazutoshi; Morita, Osamu

    2018-05-31

    Diets supplemented with alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil-which mainly consists of oleic and linolenic, linoleic acids-have potential health benefits in terms of preventing or managing obesity. Although safety of DAG oil has been extensively investigated, toxicity of ALA-DAG oil has not been well understood. Hence, the present study was conducted to clarify the potential adverse effects, if any, of ALA-DAG oil in rats (10/sex/group) fed diets containing 1.375%, 2.75%, or 5.5% ALA-DAG oil for 90 days. Compared to control rats fed rapeseed oil or ALA-triacylglycerol oil (flaxseed oil), rats receiving ALA-DAG oil did not reveal any toxicologically significant treatment-related changes as evaluated by clinical signs, functional observational battery, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, organ weight, necropsy and histopathology. The no observed adverse effect levels for dietary exposure to ALA-DAG oil for male and female rats were 2916 and 3326 mg/kg body weight/day, respectively, the highest dose tested. The findings from this study suggest that consumption of ALA-DAG oil is unlikely to cause adverse effects. Copyright © 2018. Published by Elsevier Inc.

  4. Safety of sucrose esters from Physalis peruviana L. in a 28-day repeated-dose study in mice.

    Science.gov (United States)

    Ocampo, Yanet C; Caro, Daneiva C; Rivera, David E; Franco, Luis A

    2017-06-01

    Although extracts and consumed foods from Physalis species contain sucrose esters from their glandular trichomes, there is no experimental data available on their toxicological effects. As peruvioses A and B isolated from Physalis peruviana L. calyces have proved to be effective anti-inflammatory and immunomodulatory compounds, this work aimed to investigate their sub-acute toxicity study and genotoxicity. For this, CD-1(ICR) mice were treated intraperitoneally with peruvioses at doses of 2.5, 5, and 10mg/kg/day for 28 consecutive days, to simulate therapeutic and over-therapeutic dosage levels. At the end of the treatment, animals were sacrificed and their organs weighted, and blood and tissue samples were collected. Toxicological endpoints included clinical signs; food consumption; body and organ weights; hematological and biochemical parameters; as well as macroscopic and microscopic examination of tissues. The results showed no significant differences between treated animals and control group at macroscopic, histological, molecular, and biochemical levels. In addition, a combination of mammalian erythrocyte micronucleus test, comet assay in peripheral blood cells, and Ames test, did not reveal genotoxic effects induced by peruvioses. Taken together, our data suggests that peruvioses A and B can be safely employed to treat inflammatory diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Successful Desensitization of T cell Flow Cytometry Crossmatch Positive Renal Transplant Recipients Using Plasmapheresis and Super High-Dose Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Yoichi Kakuta, MD, PhD

    2018-01-01

    Full Text Available Background. High-dose IVIG (2 g/kg alone or low-dose IVIG (100 mg/kg in conjunction with plasma exchange is typically administered as a renal transplantation desensitization therapy. Herein, we monitored changes in T cell and B cell flow cytometry crossmatch (FCXM to assess the effects of short-term super high-dose IVIG (4 g/kg administration with plasmapheresis before living-donor renal transplantation. Methods. Seventeen patients, each showing positive T cell FCXM (median ratio, ≥ 1.4 after 2 rounds of double-filtration plasmapheresis, received 4-day regimens of IVIG (1 g/kg per day over 1-week periods. T cell and B cell FCXM determinations were obtained after every IVIG dose and again up to 4 weeks after initiating IVIG to ascertain negative conversion of T cell FCXM (median ratio < 1.4. The primary study endpoint was the percentage of patients achieving T cell FCXM-negative status after the 4-dose IVIG regimen. Results. Upon completion (4 g/kg total or discontinuation of IVIG administration, 8 (47.1% of 17 patients displayed negative T cell FCXM. Based on Kaplan-Meier estimates, the cumulative T cell FCXM-negative conversion rate 4 weeks after IVIG administration initiation was 60.3%. The T cell FCXM-negative conversion rates after cumulative doses of 1, 2, 3, and 4 g/kg IVIG were 29.4%, 35.3%, 56.3%, and 46.7%, respectively. Conclusions. Desensitization of donor-specific antibody-positive renal transplant recipients seems achievable in only a subset of recipients through IVIG dosing (1 g/kg × 4 within 1 week after double-filtration plasmapheresis. The T cell FCXM-negative conversion rate resulting from a cumulative IVIG dose of 3 g/kg or greater surpassed that attained via conventional single-dose IVIG (2 g/kg protocol. This short-term high-dose IVIG desensitization protocol may be an alternative to conventional protocols for recipients with donor-specific antibody.

  6. Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

    Science.gov (United States)

    Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

    2015-09-01

    Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. Copyright © 2015. Published by Elsevier B.V.

  7. Development of immunity against viral and bacterial antigens after repeated exposures to suberythemal doses of ultraviolet light

    Directory of Open Access Journals (Sweden)

    S. A. Snopov

    2012-01-01

    Full Text Available The effects of ultraviolet (UV radiation on human infectious immunity are not well studied. On the one hand, solar and artificial UU sources have been shown to change cytokine levels in human skin, lymphocyte subpopulation counts in parepheral blood, lymphocyte DNA synthesis and prolifarative response to mitogens. On the other hand, there are just only one or two observations suggesting an influence of UV radiation on human infection course. For instance, UV irradiations have been reported to induce a reccurence of orofacial vesicular lesions caused by herpes siplex virus. Moreover, there is a lack of data concerning immune effects of suberythtemal doses of UV in spite of a long history of using them by Russian prophylactic medicine. In this work we questioned whether such suberythemal UV exposures can affect the immune responses of children to infectious conjunctivitis, to simultaneous measles and polio vaccinations and to simultaneous polio and diphtheria-tetanus vaccinations. In peripheral blood of vaccinated children we examined leukocyte counts (monocytes, neutrophils, eosinophils, lymphocytes, percentages of lymphocyte subpopulations (CD3+, CD20+, CD4+, CD8+, CD25+, HLADR+, concentrations of cytokines (IL-1 beta, TNF-alpha, IFN- amma и IL-10, DNA-synthetic activity of lymphocytes and titres of antibodies against measles and diphtheria toxin. We observed no local or systemic reactions to the vaccines in the UV-group while a moderate rise in body temperature occured in several children from unexposed group. In the blood of childeren from UV-group we found increases in CD25+ и HLADR+ cell percentages, IL- 1 beta and IL-10 concentrations, PWMinduced DNA synthesis in mononuclears, and no decreases in formation of antibodies against measles and diphreria. We concluded that suberythemal UV exposures of children modulated their further responses to imminisations perhaps through the activation of a T helper 2-like

  8. Impact of Single or Repeated Dose Intranasal Zinc-free Insulin in Young and Aged F344 Rats on Cognition, Signaling, and Brain Metabolism.

    Science.gov (United States)

    Anderson, Katie L; Frazier, Hilaree N; Maimaiti, Shaniya; Bakshi, Vikas V; Majeed, Zana R; Brewer, Lawrence D; Porter, Nada M; Lin, Ai-Ling; Thibault, Olivier

    2017-02-01

    Novel therapies have turned to delivering compounds to the brain using nasal sprays, bypassing the blood brain barrier, and enriching treatment options for brain aging and/or Alzheimer's disease. We conducted a series of in vivo experiments to test the impact of intranasal Apidra, a zinc-free insulin formulation, on the brain of young and aged F344 rats. Both single acute and repeated daily doses were compared to test the hypothesis that insulin could improve memory recall in aged memory-deficient animals. We quantified insulin signaling in different brain regions and at different times following delivery. We measured cerebral blood flow (CBF) using MRI and also characterized several brain metabolite levels using MR spectroscopy. We show that neither acute nor chronic Apidra improved memory or recall in young or aged animals. Within 2 hours of a single dose, increased insulin signaling was seen in ventral areas of the aged brains only. Although chronic Apidra was able to offset reduced CBF with aging, it also caused significant reductions in markers of neuronal integrity. Our data suggest that this zinc-free insulin formulation may actually hasten cognitive decline with age when used chronically. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Comparative analysis of transcriptomic responses to repeated-dose exposure to 2-MCPD and 3-MCPD in rat kidney, liver and testis.

    Science.gov (United States)

    Buhrke, Thorsten; Schultrich, Katharina; Braeuning, Albert; Lampen, Alfonso

    2017-08-01

    3-Chloro-1,2-propanediol (3-MCPD) and its isomer 2-chloro-1,3-propanediol (2-MCPD) are heat-induced food contaminants present in oil- and fat-containing foodstuff. Kidney and testes are among the main target organs of 3-MCPD. Almost no data on 2-MCPD toxicity are available. Here, transcriptomic responses following repeated-dose exposure of rats to non-toxic doses of 10 mg/kg body weight per day 2-MCPD or 3-MCPD for 28 days were characterized by microarray analysis of kidney, liver, and testes. 3-MCPD exerted more pronounced effects than 2-MCPD in all organs. The limited overlap between the datasets indicates that 2-MCPD and 3-MCPD do not share the same molecular mechanisms of toxicity. By combining transcriptomic data with datasets on proteomic regulation by 3-MCPD, a comprehensive view on 3-MCPD-induced regulation of glucose utilization and oxidative stress response was developed. Bioinformatic analyses revealed that Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling is likely to be involved in mediating the oxidative stress response to 3-MCPD. In summary, this study for the first time presents data on alterations in global gene expression by two important food contaminants, 2-MCPD and 3-MCPD. Data demonstrate profound differences between the effects of the two compounds and substantially broaden our knowledge on molecular details of 3-MCPD-induced disturbance of glucose utilization and redox balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

    Directory of Open Access Journals (Sweden)

    Ravi S.Talluri

    2009-10-01

    Full Text Available Objective: To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods: Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine- D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results: Following i.v. administration, the area under the curve (AUC in µM*min of generated ACV was in the order of LACV › LDACV › DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 µM*min, respectively. DLACV exhibited poor oral absorption. Cmax (µM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions: LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

  11. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing

    Science.gov (United States)

    Talluri, Ravi S.; Gaudana, Ripal; Hariharan, Sudharshan; Mitra, Ashim K.

    2009-01-01

    Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV) in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV), L-valine-D-valine-acyclovir (LDACV) and D-valine-L-valine acyclovir (DLACV) prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC) in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. Cmax (μM) and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration. PMID:23861607

  12. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir following Intravenous and Oral Administrations in Rats: A study Involving in vivo corneal Uptake of Acyclovir following Oral Dosing

    Directory of Open Access Journals (Sweden)

    Ravi S. Talluri

    2009-01-01

    Full Text Available Objective To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine-D-valine-acyclovir (LDACV and D-valine-L-valine acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results Following i.v. administration, the area under the curve (AUC in μM*min of generated ACV was in the order of LACV > LDACV > DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 μM*min, respectively. DLACV exhibited poor oral absorption. C max (μM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration.

  13. Intravenous contrast medium administration at 128 multidetector row CT pulmonary angiography: Bolus tracking versus test bolus and the implications for diagnostic quality and effective dose

    International Nuclear Information System (INIS)

    Rodrigues, J.C.L.; Mathias, H.; Negus, I.S.; Manghat, N.E.; Hamilton, M.C.K.

    2012-01-01

    Aim: To investigate the effects of a test bolus protocol contrast medium administration on diagnostic image quality in computed tomography pulmonary angiography (CTPA). Materials and methods: Fifty patients referred for exclusion of pulmonary embolism underwent CTPA using a test bolus protocol CTPA at 120 kVp and were compared with 50 patients undergoing CTPA using a standard bolus-tracking protocol at 120 kVp, via assessment of attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) seen in the pulmonary arteries (PAs). An additional group of 10 non-obese patients who underwent CTPA using a test bolus protocol performed at 100 kVp were also analysed. Mean effective dose was calculated from the dose–length product, using standard conversion factors. Results: The test bolus protocol showed significantly higher attenuation, SNR, and CNR in the pulmonary vasculature down to the segmental level compared to bolus-tracking CTPA (p < 0.0001). There was no significant difference in effective dose between the test bolus and bolus tracking cohorts. The additional group of test bolus CTPA examinations performed at 100 kVp had a significantly reduced effective dose in comparison to both test bolus CTPA at 120 kVp and bolus-tracking CTPA at 120 kVp (p < 0.005) yet maintained mean PA attenuation to segmental level significantly better than bolus-tracking CTPA performed at 120 kVp and comparable to the test bolus cohort performed at 120 kVp. Conclusion: Test bolus contrast administration should be used as an optimal protocol. Performing test bolus CTPA at 100 kVp, as opposed to 120 kVp, significantly reduces dose without compromising PA attenuation in non-obese subjects.

  14. Study of the intervention effect of Laminaria japonica polysaccharides on testis tissue in male rats exposed by repeated low-dose ionizing radiation

    International Nuclear Information System (INIS)

    Liu Jun; Luo Qiong; Cui Xiaoyan; Yang Mingliang; Yan Jun

    2010-01-01

    Objective: To investigate the effect of the Laminaria japonica polysaccharides (LJP) intervention on the male rats' testicular tissue oxidative damage which was caused by repeated low-dose local ionizing radiation. Methods: Male Wistar rats were randomly divided into control group, model group and LJP intervention group. The rats in the LJP intervention group was given with LJP. The rats in each group were exposed to 60 Co γ-ray local irradiation 7 d after adaptability breeding, once per day for 20 times in 4 weeks. Each rat was irradiated with the total dose of 2.3 Gy. The rats were killed at 1, 7 and 14 d post-irradiation, respectively. The testis and the epididymis were taken out. The contents of MDA and GSH, and the activities of SOD, LDH and GSH-Px were measured using spectrophotometer. The amorphous of testicular tissue was observed and the sperm count and viability were analyzed. Results: As compared with those in the model group, the content of MDA decreased in testicular tissue in the LJP group (t=3.66-5.03, P<0.01), while the GSH content increased. The activities of SOD, LDH and GSH-Px (t=2.77-25.52, P<0.05) and the sperm count and viability increased (t=3.11-23.08, P<0.01). Each index was more close to that in the control group 14 d post-irradiation. Conclusions: LJP can promote the recovery of testicular tissue oxidative damage caused by chronic local ionizing radiation. It has a role in promoting the spermatogenic function of male rate. (authors)

  15. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

  16. A Phase I randomized clinical trial testing the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy volunteers.

    Science.gov (United States)

    Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

    2017-11-15

    Preclinical work suggests that the metabotropic glutamate receptor subtype 5 (mGlu5) may represent a novel target to treat neuropsychiatric disorders, including alcohol use disorder and obesity. The goal of this first-in-man study was to evaluate the safety, tolerability and pharmacokinetics (PK) of GET 73 (PubChem SID: 329974174), a novel mGluR5 negative allosteric modulator. This was a double-blind, placebo-controlled, ascending dose, Phase I study conducted in healthy male volunteers in two experiments. GET 73 was administered as single ascending doses (N=48; Experiment 1; 10, 30, 100, 300, 450, 600-mg) or multiple ascending doses (N=32; Experiment 2; 100, 300, 450, 450-mg twice a day). Primary endpoints were the incidence of adverse events (AEs) among drug conditions and drug tolerability. The secondary endpoints were the PK parameters of GET 73 and its metabolite MET 2. Single GET 73 doses of up to 600-mg and repeated ascending doses of up to 450-mg twice/day were safe and well-tolerated. There were no serious or severe AEs. All AEs were mild or moderate in severity. Total GET 73 exposure increased with each increased GET 73 dose. A dose-related increase in mean maximum plasma drug concentration was observed after repeated dosing. Maximum plasma drug concentrations occurred between 0.5 and 2.05h after administration in all groups for both single and repeated doses. This first-in-human study indicates that GET 73, as single or multiple ascending doses, is safe and well-tolerated when administered to healthy male volunteers. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Intentional intravenous mercury injection

    African Journals Online (AJOL)

    In this case report, intravenous complications, treatment strategies and possible ... Mercury toxicity is commonly associated with vapour inhalation or oral ingestion, for which there exist definite treatment options. Intravenous mercury ... personality, anxiousness, irritability, insomnia, depression and drowsi- ness.[1] However ...

  18. Comparison of clinical applications of single-dose intravenous injection of mivacurium and cisatracurium in adults’ vocalcordpolyps resection under self-retaining laryngoscope

    Directory of Open Access Journals (Sweden)

    Han Fanglei

    2017-01-01

    Full Text Available Objective: Through comparing the clinical observation of mivacurium and cisatracurium in vocal polyp extraction, to study the advantage of mivacurium in vocal polyp extraction. Methods: Forty American Society of Anesthesiologists(ASA physical status I~II patients for vocal polyp extraction, aged 18~60 years old, were randomly divided into two groups as Mivacurium injection group(Group M and Cis-atracurium injection group(Group C, each group includes 20 subjects. None of the patients are allergic, has serious diseases of cardiovascular system, liver or kidney.None of them has asthma, airway high response, difficult airway or neuromuscular diseases.Those patients who use beta-blockers or calcium channel blockers for a long time were excluded .All the subjects had the same premedication, fasting and fluid fobidden time. All the subjects who get into the operating room get the routine monitoring of electrocardiogram(EEG, blood pressure(BP, heart rate(HR, pulse oxygen saturation(SpO2 and the TOF WATCH SX. Each group gives the same medicine other than the muscle relaxant during induction of general anesthesia to do the vocal polyp extraction by the same experienced operator. Two groups were recorded in each index of anesthesia induction and tracheal intubation conditions, operation conditions, anesthesia, muscle relaxation monitoring. Results: There are no statistically significant in Cormack-Lehane grading system,Cooper’s grading system and operation satifaction(p>0.05. 2. Group A have shorter intubation time than Group B(p0.05. Conclusion: 1. A single intubating dose of mivacurium can provide similar intubation and surgeon satisfaction for the vocal polyp extraction. 2. Compared with cis-atracurium, mivacurium can shorten the intubation time and the recovery time of anesthesia. The adverse reactions of mivacurium is mild, and it has less Residual muscle relaxation. Therefore mivacurium is more suitable for the vocal polyp extraction than cis-atracurium.

  19. Collaborative work on evaluation of ovarian toxicity. 13) Two- or four-week repeated dose studies and fertility study of PPAR alpha/gamma dual agonist in female rats.

    Science.gov (United States)

    Sato, Norihiro; Uchida, Keisuke; Nakajima, Mikio; Watanabe, Atsushi; Kohira, Terutomo

    2009-01-01

    The main focus of this study was to determine the optimal dosing period in a repeated dose toxicity study based on toxic effects as assessed by ovarian morphological changes. To assess morphological and functional changes induced in the ovary by a peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual agonist, the compound was administered to female rats at dose levels of 0, 4, 20, and 100 mg/kg/day in a repeated dose toxicity study for 2 or 4 weeks, and from 2 weeks prior to mating to Day 7 of pregnancy in a female fertility study. In the repeated dose toxicity study, an increase in atresia of large follicles, a decrease in corpora lutea, and an increase in stromal cells were observed in the treated groups. In addition, the granulosa cell exfoliations into antrum of large follicles and corpora lutea with retained oocyte are morphological characteristics induced by this compound, and they might be related with abnormal condition of ovulation. In the female fertility study, the pregnancy rate tended to decrease in the 100 mg/kg/day group. At necropsy, decreases in the number of corpora lutea, implantations and live embryos were noted in the 20 and 100 mg/kg/day group. No changes were observed in animals given 4 mg/kg/day. These findings indicated that histopathological changes in the ovary are important endpoints for evaluation of drugs inducing ovarian damage. In conclusion, a 2-week administration period is sufficient to detect ovarian toxicity of this test compound in the repeated dose toxicity study.

  20. Intravenous iron supplementation in children on hemodialysis.

    NARCIS (Netherlands)

    Leijn, E.; Monnens, L.A.H.; Cornelissen, E.A.M.

    2004-01-01

    BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in

  1. Intravenous paracetamol overdose in a paediatric patient

    NARCIS (Netherlands)

    Broeks, Ilse J.; Van Roon, Eric N.; Van Pinxteren-Nagler, Evelyn; De Vries, Tjalling W.

    2013-01-01

    BACKGROUND: Paracetamol is a widely used drug in children. In therapeutic doses, paracetamol has an excellent safety profile. Since the introduction of the intravenous form in 2004, only three reports of accidental overdose in children have been published. The low number probably is due to

  2. Administration and monitoring of intravenous anesthetics

    NARCIS (Netherlands)

    Sahinovic, Marko M.; Absalom, Anthony R.; Struys, Michel M. R. F.

    2010-01-01

    Purpose of review The importance of accuracy in controlling the dose-response relation for intravenous anesthetics is directly related to the importance of optimizing the efficacy and quality of anesthesia while minimizing adverse drug effects. Therefore, it is important to measure and control all

  3. Single Intravenous Dose of Oritavancin for Treatment of Acute Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: Summary of Safety Analysis from the Phase 3 SOLO Studies.

    Science.gov (United States)

    Corey, G Ralph; Loutit, Jeffery; Moeck, Greg; Wikler, Matthew; Dudley, Michael N; O'Riordan, William

    2018-04-01

    Oritavancin is a lipoglycopeptide with bactericidal activity against Gram-positive organisms. Its rapid concentration-dependent bactericidal activity and long elimination half-life allow single-dose treatment of acute bacterial skin and skin structure infections (ABSSSI). SOLO I and SOLO II were randomized, double-blind studies evaluating the efficacy and safety of a single 1,200-mg intravenous (i.v.) dose of oritavancin versus twice-daily i.v. vancomycin for 7 to 10 days in ABSSSI patients. Safety data from both studies were pooled for safety analysis. The database comprised pooled safety data for 976 oritavancin-treated patients and 983 vancomycin-treated patients. The incidences of adverse events, serious adverse events, and discontinuations due to adverse events were similar for oritavancin (55.3, 5.8, and 3.7%, respectively) and vancomycin (56.9, 5.9, and 4.2%, respectively). The median time to onset (3.8 days versus 3.1 days, respectively) and the duration (3.0 days for both groups) of adverse events were also similar between the two groups. The most frequently reported events were nausea, headache, and vomiting. Greater than 90% of all events were mild or moderate in severity. There were slightly more infections and infestations, abscesses or cellulitis, and hepatic and cardiac adverse events in the oritavancin group; however, more than 80% of these events were mild or moderate. Subgroup analyses did not identify clinically meaningful differences in the incidence of adverse events attributed to oritavancin. A single 1,200-mg dose of oritavancin was well tolerated and had a safety profile similar to that of twice-daily vancomycin. The long elimination half-life of oritavancin compared to that of vancomycin did not result in a clinically meaningful delay to the onset or prolongation of adverse events. (This study has been registered at ClinicalTrials.gov under registration no. NCT01252719 and NCT01252732.). Copyright © 2018 American Society for Microbiology.

  4. Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33.

    Science.gov (United States)

    Ritter, G; Cohen, L S; Williams, C; Richards, E C; Old, L J; Welt, S

    2001-09-15

    Mouse monoclonal antibody A33 (mAb A33) recognizes a M(r) 43,000 cell surface glycoprotein (designated A33) expressed in human colonic epithelium and colon cancer but absent from most other normal tissues. In patients, mAb A33 localizes with high specificity to colon cancer and is retained for up to 6 weeks in the cancer but cleared rapidly from normal colon (5-6 days). As a carrier of (125)I or (131)I, mAb A33 has shown antitumor activity. Induction of strong human anti-mouse antibody (immunoglobulin; HAMA) responses in patients, however, limits the use of the murine mAb A33 to very few injections. A humanized version of this antibody (huAb A33) has been prepared for Phase I and II clinical studies in patients with colon cancer. In those studies, immunogenicity of huAb A33 has been monitored using a novel, highly sensitive BIACORE method, which allows measurement of human anti-human antibodies (HAHAs) without the use of secondary reagents. We found that 63% (26 of 41) of the patients treated with repeated doses of huAb A33 developed HAHAs against a conformational antigenic determinant located in the V(L) and V(H) regions of huAb A33. Detailed serological analysis showed two distinct types of HAHAs. HAHA of type I (49% of patients) was characterized by an early onset with peak HAHA levels after 2 weeks of treatment, which declined with ongoing huAb A33 treatment. HAHA of type II (17% of patients) was characterized by a typically later onset of HAHA than in type I and by progressively increasing HAHA levels with each subsequent huAb A33 administration. Colon cancer patients with type I HAHAs did not develop infusion-related adverse events. In contrast, HAHA of type II was indicative of infusion-related adverse events. By using this new method, we were able to distinguish these two types of HAHAs in patients while on antibody treatment, allowing patients to be removed from study prior to the onset of severe infusion-related adverse events.

  5. Prediction of drug terminal half-life and terminal volume of distribution after intravenous dosing based on drug clearance, steady-state volume of distribution, and physiological parameters of the body.

    Science.gov (United States)

    Berezhkovskiy, Leonid M

    2013-02-01

    The steady state, V(ss), terminal volume of distribution, V(β), and the terminal half-life, t(1/2), are commonly obtained from the drug plasma concentration-time profile, C(p)(t), following intravenous dosing. Unlike V(ss) that can be calculated based on the physicochemical properties of drugs considering the equilibrium partitioning between plasma and organ tissues, t(1/2) and V(β) cannot be calculated that way because they depend on the rates of drug transfer between blood and tissues. Considering the physiological pharmacokinetic model pertinent to the terminal phase of drug elimination, a novel equation that calculates t(1/2) (and consequently V(β)) was derived. It turns out that V(ss), the total body clearance, Cl, equilibrium blood-plasma concentration ratio, r; and the physiological parameters of the body such as cardiac output, and blood and tissue volumes are sufficient for determination of terminal kinetics. Calculation of t(1/2) by the obtained equation appears to be in good agreement with the experimentally observed vales of this parameter in pharmacokinetic studies in rat, monkey, dog, and human. The equation for the determination of the pre-exponent of the terminal phase of C(p)(t) is also found. The obtained equation allows to predict t(1/2) in human assuming that V(ss) and Cl were either obtained by allometric scaling or, respectively, calculated in silico or based on in vitro drug stability measurements. For compounds that have high clearance, the derived equation may be applied to calculate r just using the routine data on Cl, V(ss), and t(1/2), rather than doing the in vitro assay to measure this parameter. Copyright © 2012 Wiley Periodicals, Inc.

  6. Acute Toxicity of Intravenously Administered Titanium Dioxide Nanoparticles in Mice

    OpenAIRE

    Xu, Jiaying; Shi, Hongbo; Ruth, Magaye; Yu, Hongsheng; Lazar, Lissy; Zou, Baobo; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

    2013-01-01

    BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochem...

  7. A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

    International Nuclear Information System (INIS)

    Mason, Jay W; Moon, Thomas E; O’Boyle, Erin; Dietz, Albert

    2014-01-01

    Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO), intravenous (IV), and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC) injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals. This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF) for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated. The upper one-sided 95% confidence interval (CI) for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36) at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours) and slow elimination (mean half-life 18.6 hours; systemic clearance 20.2 L/hour) of granisetron versus the expected early peak concentration and elimination of granisetron IV. APF530 SC was well tolerated. Adverse events, most commonly constipation and SC injection-site reactions, were generally mild and quickly resolved. APF530 1 g SC did

  8. A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation

    Directory of Open Access Journals (Sweden)

    Mason JW

    2014-03-01

    Full Text Available Jay W Mason,1 Thomas E Moon,2 Erin O’Boyle,3 Albert Dietz41Department of Medicine, University of Utah, Salt Lake City, UT, 2Tarizona eHealth Services, Inc., San Carlos, CA, 3AP Pharma, Redwood City, CA, 4Spaulding Clinical Research, West Bend, WI, USABackground: Regulatory concern about potential QT-interval prolongation by serotonin-receptor antagonist antiemetics prompted product-label changes. The first-generation serotonin-receptor antagonist granisetron is available in oral (PO, intravenous (IV, and transdermal formulations. APF530 is a formulation that provides sustained release of granisetron when administered as a single subcutaneous (SC injection. The Phase I study reported here evaluated effects of APF530 on electrocardiographic intervals.Methods: This single-site, double-blind, placebo-controlled, four-period crossover trial randomized healthy men and women to receive varying sequences of APF530 1 g SC, granisetron 50 μg/kg IV, moxifloxacin 400 mg PO, and placebo. Subjects were assessed for 49 hours after each treatment. The primary objective was to evaluate differences between baseline-adjusted, heart rate-corrected QT-interval change using the Fridericia rate correction (dQTcF for APF530 1 g SC and placebo. Electrocardiograms were performed at various times throughout the assessment period. Pharmacokinetics and safety were evaluated.Results: The upper one-sided 95% confidence interval (CI for mean baseline-adjusted dQTcF at each post-dose time point between APF530 and placebo excluded 10 ms, indicating that APF530 1 g SC had no clinically significant effect on QTcF. Maximum observed QTcF change was 4.15 ms (90% CI, 0.94 to 7.36 at Hour 3. No clinically significant changes in other electrocardiogram intervals were observed. APF530 SC pharmacokinetics were as expected, with slow absorption (maximum plasma concentration 35.8 ng/mL, median time to maximum plasma concentration 11.1 hours and slow elimination (mean half-life 18.6 hours

  9. Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness

    Directory of Open Access Journals (Sweden)

    Zhilu Zou

    2017-01-01

    Full Text Available Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A- CREB (cAMP response element binding protein and NMDA (N-methyl-D-aspartate signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.

  10. Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness.

    Science.gov (United States)

    Zou, Zhilu; Chen, Yin; Shen, Qinqin; Guo, Xiaoyan; Zhang, Yuxuan; Chen, Gang

    2017-01-01

    Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.

  11. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    evaluating the deployment repeatability builds upon the testing or analysis of deployment kinematics (Chapter 6) and adds repetition. Introduction...material yield or failure during a test. For the purposes of this chapter, zero shift will refer to permanent changes in the structure, while reversible ...the content of other chapters in this book: Gravity Compensation (Chapter 4) and Deployment Kinematics and Dynamics (Chapter 6). Repeating the

  12. Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

    Science.gov (United States)

    Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

    2016-05-01

    The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P agents. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Repeated dose 28-day oral toxicity study in Wistar rats with a mixture of five pesticides often found as residues in food: alphacypermethrin, bromopropylate, carbendazim, chlorpyrifos and mancozeb

    DEFF Research Database (Denmark)

    Jacobsen, H.; Østergaard, G.; Lam, Henrik Rye

    2004-01-01

    Six dose groups of 8 male and female rats respectively received a daily dose equivalent to 0, 0.15, 0.006, 0.03, 0.15 or 0.3 mg/kg b.w./day chlorpyrifos (groups 1-6) and the last four dose groups (groups 3-6) received in addition daily doses equivalent to 18 mg/kg b.w./day alphacypermethrin, 30 mg...... of acetylcholinesterase activity in plasma and brain by chlorpyrifos was not enhanced by coadministration of the other four pesticides. Effects were seen in liver, thyroid, thymus and blood in the combination groups. However, identification of the pesticide(s) responsible for these changes would require further studies...

  14. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster

    DEFF Research Database (Denmark)

    Langkilde, Søren; Mandimika, T.; Schrøder, Malene

    2009-01-01

    of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios...... intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7....

  15. Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection.

    Science.gov (United States)

    Adegnika, Ayola A; Zinsou, Jeannot F; Issifou, Saadou; Ateba-Ngoa, Ulysse; Kassa, Roland F; Feugap, Eliane N; Honkpehedji, Yabo J; Dejon Agobe, Jean-Claude; Kenguele, Hilaire M; Massinga-Loembe, Marguerite; Agnandji, Selidji T; Mordmüller, Benjamin; Ramharter, Michael; Yazdanbakhsh, Maria; Kremsner, Peter G; Lell, Bertrand

    2014-05-01

    In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).

  16. A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats.

    Science.gov (United States)

    Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Mizuta, Yasuko; Yoshida, Midori; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2014-04-01

    3-monochloropropane-1,2-diol (3-MCPD), a rat renal and testicular carcinogen, has been reported to occur in various foods and food ingredients as free or esterified forms. Since reports about toxicity of 3-MCPD esters are limited, we conducted a 13-week rat subchronic toxicity study of 3-MCPD esters (palmitate diester: CDP, palmitate monoester: CMP, oleate diester: CDO). We administered a carcinogenic dose (3.6 × 10(-4) mol/kg B.W./day) of 3-MCPD or these esters at equimolar concentrations and two 1/4 lower doses by gavage with olive oil as a vehicle five times a week for 13 weeks to F344 male and female rats. As a result, five out of ten 3-MCPD-treated females died from acute renal tubular necrosis, but none of the ester-treated rats. Decreased HGB was observed in all high-dose 3-MCPD fatty acid ester-treated rats, except CDO-treated males. The absolute and relative kidney weights were significantly increased in the ester-treated rats at medium and high doses. Relative liver weights were significantly increased in the esters-treated rat at high dose, except for CMP females. Significant increase in apoptotic epithelial cells in the initial segment of the epididymis of high-dose ester-treated males was also observed. The results suggested that although acute renal toxicity was lower than 3-MCPD, these three 3-MCPD fatty acid esters have the potential to exert subchronic toxicity to the rat kidneys and epididymis, to a similar degree as 3-MCPD under the present conditions. NOAELs (no-observed-adverse-effect levels) of CDP, CMP and CDO were suggested to be 14, 8 and 15 mg/kg B.W./day, respectively.

  17. Repeating Marx

    DEFF Research Database (Denmark)

    Fuchs, Christian; Monticelli, Lara

    2018-01-01

    This introduction sets out the context of the special issue “Karl Marx @ 200: Debating Capitalism & Perspectives for the Future of Radical Theory”, which was published on the occasion of Marx’s bicentenary on 5 May 2018. First, we give a brief overview of contemporary capitalism’s development...... and its crises. Second, we argue that it is important to repeat Marx today. Third, we reflect on lessons learned from 200 years of struggles for alternatives to capitalism. Fourth, we give an overview of the contributions in this special issue. Taken together, the contributions in this special issue show...... that Marx’s theory and politics remain key inspirations for understanding exploitation and domination in 21st-century society and for struggles that aim to overcome these phenomena and establishing a just and fair society. We need to repeat Marx today....

  18. Deployment Repeatability

    Science.gov (United States)

    2016-08-31

    large cohort of trials to spot unusual cases. However, deployment repeatability is inherently a nonlinear phenomenon, which makes modeling difficult...and GEMS tip position were both tracked during ground testing by a laser target tracking system. Earlier SAILMAST testing in 2005 [8] used...recalls the strategy used by SRTM, where a constellation of lights was installed at the tip of the boom and a modified star tracker was used to track tip

  19. Computed tomography intravenous cholangiography

    International Nuclear Information System (INIS)

    Nascimento, S.; Murray, W.; Wilson, P.

    1997-01-01

    Indications for direct visualization of the bile ducts include bile duct dilatation demonstrated by ultrasound or computed tomography (CT) scanning, where the cause of the bile duct dilatation is uncertain or where the anatomy of bile duct obstruction needs further clarification. Another indication is right upper quadrant pain, particularly in a post-cholecystectomy patient, where choledocholithiasis is suspected. A possible new indication is pre-operative evaluation prior to laparoscopic cholecystectomy. The bile ducts are usually studied by endoscopic retrograde cholangiopancreatography (ERCP), or, less commonly, trans-hepatic cholangiography. The old technique of intravenous cholangiography has fallen into disrepute because of inconsistent bile-duct opacification. The advent of spiral CT scanning has renewed interest in intravenous cholangiography. The CT technique is very sensitive to the contrast agent in the bile ducts, and angiographic and three-dimensional reconstructions of the biliary tree can readily be obtained using the CT intravenous cholangiogram technique (CT IVC). Seven patients have been studied using this CT IVC technique, between February 1995 and June 1996, and are the subject of the present report. Eight further studies have since been performed. The results suggest that CT IVC could replace ERCP as the primary means of direct cholangiography, where pancreatic duct visualization is not required. (authors)

  20. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR)

    NARCIS (Netherlands)

    Rubbert-Roth, Andrea; Tak, Paul P.; Zerbini, Cristiano; Tremblay, Jean-Luc; Carreño, Luis; Armstrong, Gillian; Collinson, Neil; Shaw, Tim M.

    2010-01-01

    Methods. Patients with active RA despite stable MTX (10-25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 x 500 and 2 x 500 mg; 2 x 500 and 2 x 1000 mg (dose escalation); and 2 x 1000 and 2 x 1000 mg. The primary endpoint

  1. Dose-escalated CHOP plus etoposide (MegaCHOEP) followed by repeated stem cell transplantation for primary treatment of aggressive high-risk non-Hodgkin lymphoma

    NARCIS (Netherlands)

    Glass, B; Kloess, M; Bentz, M; Schlimok, G; Berdel, WE; Feller, A; Trumper, L; Loeffler, M; Pfreundschuh, M; Schmitz, N

    2006-01-01

    Feasibility, safety, and efficacy of a 4-course high-dose chemotherapy (HDT) protocol including autologous stem cell transplantation (SCT) after courses 2, 3, and 4 was investigated in 110 patients, aged 18 to 60 years, with primary diagnosis of aggressive NHL (aNHL), and lactic dehydrogenase (LDH)

  2. Drug- not carrier-dependent haematological and biochemical changes in a repeated dose study of cyclosporine encapsulated polyester nano- and micro-particles: Size does not matter

    International Nuclear Information System (INIS)

    Venkatpurwar, V.P.; Rhodes, S.; Oien, K.A.; Elliott, M.A.; Tekwe, C.D.; Jørgensen, H.G.; Kumar, M.N.V. Ravi

    2015-01-01

    Highlights: • The particulate delivery allows an increase in dose range without accrual of toxicities. • The altered haematological and biochemical changes are drug, but not particle dependent. • PLGA nano/microparticles are safe on subacute peroral dosing over 28 days. • Nano-toxicology, drug needs to be considered. - Abstract: Biodegradable nanoparticles are being considered more often as drug carriers to address pharmacokinetic/pharmacodynamic issues, yet nano-product safety has not been systematically proven. In this study, haematological, biochemical and histological parameters were examined on 28 day daily dosing of rats with nano- or micro-particle encapsulated cyclosporine (CsA) to confirm if any changes observed were drug or carrier dependent. CsA encapsulated poly(lactide-co-glycolide) [PLGA] nano- (nCsA) and micro-particles (mCsA) were prepared by emulsion techniques. CsA (15, 30, 45 mg/kg) were administered by oral gavage to Sprague Dawley (SD) rats over 28 days. Haematological and biochemical metrics were followed with tissue histology performed on sacrifice. Whether presented as nCsA or mCsA, 45 mg/kg dose caused significant loss of body weight and lowered food consumption compared to untreated control. Across the doses, both nCsA and mCsA produce significant decreases in lymphocyte numbers compared to controls, commensurate with the proprietary product, Neoral ® 15. Dosing with nCsA showed higher serum drug levels than mCsA presumably owing to the smaller particle size facilitating absorption. The treatment had no noticeable effects on inflammatory/oxidative stress markers or antioxidant enzyme levels, except an increase in ceruloplasmin (CP) levels for high dose nCsA/mCsA group. Further, only subtle, sub-lethal changes were observed in histology of nCsA/mCsA treated rat organs. Blank (drug-free) particles did not induce changes in the parameters studied. Therefore, it is extremely important that the encapsulated drug in the nano-products is

  3. Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration

    Directory of Open Access Journals (Sweden)

    Berkó S

    2016-05-01

    Full Text Available Szilvia Berkó,1,* Kálmán F Szűcs,2,* Boglárka Balázs,1,3 Erzsébet Csányi,1 Gábor Varju,4 Anita Sztojkov-Ivanov,2 Mária Budai-Szűcs,1 Judit Bóta,2 Róbert Gáspár2 1Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 2Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 3Gedeon Richter Plc., Budapest, 4Dr Derm Clinic of Anti-Aging Dermatology, Aesthetic Laser and Plastic Surgery, Budapest, Hungary *These authors contributed equally to this work Purpose: Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. Methods: The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Results: Both intravenously and EP-administered neostigmine (0.2–66.7 µg/kg increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 µg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. Conclusion: The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice. Keywords: transdermal

  4. Action of 50 R X-ray doses on the breeding function of C3H strain mice - effect of splitting the dose, action of repeated irradiations on successive generations

    International Nuclear Information System (INIS)

    Alix, D.

    1965-01-01

    X-rays exposure effect was studied on C3H strain mice, at the standpoint of the effects produced on breeding function. The method used with this purpose was the following: single doses 20 - 30 - 40 and 50 R/dose, fractional doses: 50 R/total dose, divided in 2 - 5 - 10 or 25 irradiations distributed in one month duration. The offsprings were irradiated at the same doses than the parents, consanguinity being maintained. Statistical treatment of results was carried out, that led at the following conclusions: 1) Couples receiving single exposure of 50 R or two exposures of 25 R at one month interval give comparable results. Fractional doses do not involve the slightest diminution of X-rays effect. 2) 30 R exposure brings about a decrease in fertility, with an increase in abortions. Fertility of 20 R irradiated couples remains below controls. 3) After ten times 5 R and twenty-five 2 R, the number of abortions is the largest. Ovarian function is particularly sensitive to X-rays; one may think that twenty-five 2 R give injuries conditioning non-viability of conception products, smaller doses should produce mutations and yield births of altered genotype individuals. (author) [fr

  5. Adherence of radiopharmaceuticals and labeled cells to intravenous tubing

    International Nuclear Information System (INIS)

    Segall, G.M.; Gurevich, N.; McDougall, I.R.

    1986-01-01

    A survey of 67 nuclear medicine departments revealed no agreement on which radiolabeled agents could be injected through intravenous lines (IVs) and which required direct venipuncture. Labeled cells and several common radiopharmaceuticals were tested for adherence to intravenous tubing. Residual activity remaining in the tubing after an adequate flush was less than 1% of the injected dose in each case. Administration of radiolabeled agents through existing IVs is an acceptable alternative to direct venipuncture in many cases

  6. Action of thrice- and five-times repeated exposures of rats to a low dose of X-rays on the carbonhydrate-energy metabolism of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Mironova, T M; Cherkasova, L S; Fomichenko, V G [AN Belorusskoj SSR, Minsk. Inst. Fiziologii

    1975-01-01

    Rats have been subjected to whole-body X-irradiation either 3 times with 2- and 3-day intervals and the total dose of 40 R or 5 times with 3-day intervals and the total dose of 50 R. One day after the end of the 3 times irradiation course the following concentrational changes have been observed in brain hemispheres: increase in the biologically active glycogen-protein complex and creatine phosphate, and decrease in glucose-1-phosphate; after the 5 times irradiation course the changes have not been significant, though an elevated corticosterone level in blood has been noted in both cases. 9 to 15 days after the quintuple irradiation a discoordination of glycogenolysis processes against the background of lowered corticosterone level has been observed. The trend towards restitution of metabolism becomes apparent at the normal hormone level. The glycogenlipid complex has probably an adaptive function.

  7. A 14-day repeated-dose oral toxicological evaluation of an isothiocyanate-enriched hydro-alcoholic extract from Moringa oleifera Lam. seeds in rats.

    Science.gov (United States)

    Kim, Youjin; Jaja-Chimedza, Asha; Merrill, Daniel; Mendes, Odete; Raskin, Ilya

    2018-01-01

    A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5 males/5 females per group) were gavaged daily for 14 d with the vehicle control or MSE, at 78 (low), 257 (mid-low), 772 (mid-high), or 2571 (high) mg/kg bw/d, standardized to MIC-1 (30, 100, 300, or 1000 mg/kg bw/d, respectively). Toxicological endpoints included body weight and weight gain, food consumption and feed efficiency, clinical observations, hematology, gross necropsy and histopathology, and relative organ weights. Mortality was only observed in the high dose group animals, both male and female, representing decreases in body weight/weight gain and food consumption/feed efficiency. Irregular respiratory patterns and piloerection were major clinical observations found primarily in the mid-high and high dose group animals. In the high dose group, gastrointestinal distention and stomach discoloration were observed in non-surviving males and females, and degeneration and necrosis of the testicular germinal cells and epididymal cells were also observed in a non-surviving male. Increased liver weights were found in females in the mid-high and high dose groups. Animals in the low and mid-low groups did not exhibit adverse effects of MSE (100 mg/kg bw/d MIC-1). A no observed adverse effect level (NOAEL) of the standardized MSE was determined as 257 mg/kg bw/d providing 100 mg/kg bw/d MIC-1.

  8. ORAL IBOPAMINE SUBSTITUTION IN PATIENTS WITH INTRAVENOUS DOPAMINE DEPENDENCE

    NARCIS (Netherlands)

    GIRBES, ARJ; MILNER, AR; MCCLOSKEY, BV; ZWAVELING, JH; VANVELDHUISEN, DJ; ZIJLSTRA, JG; LIE, KI

    1995-01-01

    In a prospective open study we evaluated whether intravenous dopamine infusions can be safely switched to enterally administered ibopamine in dopamine-dependent patients. Six patients defined as being clinically stable, normovolaemic, but dopamine dependent, i.e. with repeated inability to stop

  9. [Efficacy of intravenous phenobarbital treatment for status epilepticus].

    Science.gov (United States)

    Muramoto, Emiko; Mizobuchi, Masahiro; Sumi, Yoshihiro; Sako, Kazuya; Nihira, Atsuko; Takeuchi, Akiko; Nakamura, Hirohiko

    2013-08-01

    Intravenous phenobarbital (IV-PB) therapy was launched in Japan in October 2008. We retrospectively investigated its efficacy and tolerability in patients with status epilepticus. Forty-three consecutive patients received IV-PB for status epilepticus between June 2009 and April 2011. Among them, 39 patients had underlying diseases, which included acute diseases in 19 patients and chronic conditions in 20 patients. Although 18 patients had been taking antiepileptic drugs (AEDs) before the occurrence of status epilepticus, the blood AED concentrations in 8 patients was below the therapeutic levels. Before the administration of IV-PB, 39 patients were treated with intravenous benzodiazepine, 17 patients were treated with intravenous phenytoin, and 15 patients with intravenous infusion of lidocaine. The initial doses of IV-PB ranged from 125 to 1,250 mg (1.9-20.0 mg/kg). Additional doses of IV-PB were required in 12 patients. Seizures were controlled in 35 patients (81%) after IV-PB administration. Cessation of status epilepticus was attained in 24 patients after the initial dose and in 11 patients after additional doses. There were no serious adverse effects, although respiratory suppression was observed in 3 patients and drug eruption was observed in 1 patient. IV-PB is relatively safe and effective for controlling status epilepticus. If the first dose is not effective, additional doses are required up to the recommended maximum dose.

  10. Contrast agent choice for intravenous coronary angiography

    International Nuclear Information System (INIS)

    Zeman, H.D.; Siddons, D.P.

    1989-01-01

    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation x-rays and an iodine containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic x-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the x-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation x-rays is visualizing a coronary artery through the left ventricle or aorta which also contains a contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth

  11. Clinical outcomes of intravenous immunoglobulin therapy in refractory uveitis.

    Science.gov (United States)

    Garcia-Geremias, M; Carreño, E; Epps, S J; Lee, R W J; Dick, A D

    2015-04-01

    Intravenous immunoglobulin (IVIg) therapy has multiple mechanisms of immunomodulatory action. We wished therefore to assess its efficacy in a spectrum of patients with refractory uveitis. Retrospective review of clinical charts was conducted to document response to IVIg treatment in consecutive patients with treatment-refractory uveitis. Main outcome measures were control of intraocular inflammation, visual acuity, progression of the disease, and complications. Four (two male) patients, with a mean age at the beginning of the treatment of 47 years (range: 39-64), were included in the study. Indication for treatment was patients with active non-infectious uveitis refractory to steroids and immunomodulatory therapy. All patients received a course of 0.5 g/kg per day of IVIg for three consecutive days, repeating this course at a mean of 11 week (range: 2-39 weeks) intervals when indicated clinically. The median duration of the IVIg therapy was 7 months (range: 3-14 months). In three patients treatment resulted in stabilisation and prevention of progression of the disease, and additionally in two patients it facilitated a decrease in prednisolone dose. Treatment failed to induce long-term remission in one patient with recurrence of macular oedema. IVIg was well tolerated with neither immediate nor longer-term adverse events observed. In three out of four cases IVIg was an effective adjunctive therapy and well tolerated for the management of treatment-refractory uveitis.

  12. Argemone oil, an edible oil adulterant, induces systemic immunosuppression in Balb/c mice in an oral 28 days repeated dose toxicity study.

    Science.gov (United States)

    Mandal, Payal; Tewari, Prachi; Kumar, Sachin; Yadav, Sarika; Ayanur, Anjaneya; Chaturvedi, Rajnish K; Das, Mukul; Tripathi, Anurag

    2018-05-01

    Consumption of edible oils contaminated with Argemone oil (AO) leads to a clinical condition called "Epidemic dropsy". Earlier studies have reported that metabolism and oxidative stress primarily contributes to AO toxicity, however, the involvement of immune system has not been assessed so far. Therefore, the present study was undertaken to systematically assess the effect of AO exposure on the function of immune system in Balb/c mice. The repeated exposure of AO for 28 days caused prominent regression of spleen and thymus; severe inflammatory changes in spleen depicted by the loss of distinct follicles, increased megakaryocyte infiltration, and enhanced expression levels of inflammatory markers (iNOS & COX-2). At the functional level, AO exposure significantly abrogated the mixed lymphocyte reaction and mitogen-stimulated lymphoproliferative activity of T and B cells, which is reflective of profound lymphocyte dysfunction upon antigen exposure. In concordance with the loss in functional activity of lymphocytes in AO exposed animals, it was found the AO altered the relative percentage of CD3 + , CD4 + , and CD28  +  T cells. Further, there was a marked decrease in the relative distribution of cells with prominent MHC I and CD1d expression in AO exposed splenocytes. Moreover, reduced levels of immune stimulatory cytokines (TNF-α, IFN-γ, IL-2, IL-4, and IL-6), and increased levels of immunosuppressive cytokine IL-10 were detected in the serum of AO treated mice. Along with T and B cells, AO exposure also affected the phenotype and activation status of macrophages suggesting the inclination towards "alternative activation of macrophages". Altogether, these functional changes in the immune cells are contributing factors in AO induced immunosuppression. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Long-term Outcomes With Planned Multistage Reduced Dose Repeat Stereotactic Radiosurgery for Treatment of Inoperable High-Grade Arteriovenous Malformations: An Observational Retrospective Cohort Study.

    Science.gov (United States)

    Marciscano, Ariel E; Huang, Judy; Tamargo, Rafael J; Hu, Chen; Khattab, Mohamed H; Aggarwal, Sameer; Lim, Michael; Redmond, Kristin J; Rigamonti, Daniele; Kleinberg, Lawrence R

    2017-07-01

    There is no consensus regarding the optimal management of inoperable high-grade arteriovenous malformations (AVMs). This long-term study of 42 patients with high-grade AVMs reports obliteration and adverse event (AE) rates using planned multistage repeat stereotactic radiosurgery (SRS). To evaluate the efficacy and safety of multistage SRS with treatment of the entire AVM nidus at each treatment session to achieve complete obliteration of high-grade AVMs. Patients with high-grade Spetzler-Martin (S-M) III-V AVMs treated with at least 2 multistage SRS treatments from 1989 to 2013. Clinical outcomes of obliteration rate, minor/major AEs, and treatment characteristics were collected. Forty-two patients met inclusion criteria (n = 26, S-M III; n = 13, S-M IV; n = 3, S-M V) with a median follow-up was 9.5 yr after first SRS. Median number of SRS treatment stages was 2, and median interval between stages was 3.5 yr. Twenty-two patients underwent pre-SRS embolization. Complete AVM obliteration rate was 38%, and the median time to obliteration was 9.7 yr. On multivariate analysis, higher S-M grade was significantly associated ( P = .04) failure to achieve obliteration. Twenty-seven post-SRS AEs were observed, and the post-SRS intracranial hemorrhage rate was 0.027 events per patient year. Treatment of high-grade AVMs with multistage SRS achieves AVM obliteration in a meaningful proportion of patients with acceptable AE rates. Lower obliteration rates were associated with higher S-M grade and pre-SRS embolization. This approach should be considered with caution, as partial obliteration does not protect from hemorrhage. Copyright © 2017 by the Congress of Neurological Surgeons

  14. Intravenous versus oral etoposide

    DEFF Research Database (Denmark)

    Ali, Abir Salwa; Grönberg, Malin; Langer, Seppo W.

    2018-01-01

    High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently...... administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter- and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS......) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (≤ 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS...

  15. [Value of intravenous immunoglobulins. A case of Guillain-Barré syndrome].

    Science.gov (United States)

    Hidou, M; Olivier, J; Vivant, J F

    1992-01-01

    A case of severe Guillain-Barré syndrome (GBS) was treated with high dose intravenous immunoglobulin (IVIG), 400 mg.kg-1.days-1, over three consecutive days. The treatment was repeated once. We observed a time-related response between immunoglobulins administration and clinical improvement. The pathologic lesions of the GBS suggest that this syndrome has an immunologic basis: a humoral factor is probably not the only immunological mechanism and cellular mechanisms are also likely to be of importance. Specific mechanisms might also be present in GBS, such as anti-idiotypic suppression of autoantibodies, and elimination of circulating immune complexes. Treatment with IVIG might have several therapeutic advantages over plasmapheresis: IVIG is easily infused without any delay, is easily available and has been used widely without serious complications.

  16. Methods of preparing and using intravenous nutrient compositions

    International Nuclear Information System (INIS)

    Beigler, M.A.; Koury, A.J.

    1983-01-01

    A method for preparing a stable, dry-packaged, sterile, nutrient composition which upon addition of sterile, pyrogen-free water is suitable for intravenous administration to a mammal, including a human, is described. The method comprises providing the nutrients in a specific dry form and state of physical purity acceptable for intravenous administration, sealing the nutrients in a particular type of container adapted to receive and dispense sterile fluids and subjecting the container and its sealed contents to a sterilizing, nondestructive dose of ionizing radiation. The method results in a packaged, sterile nutrient composition which may be dissolved by the addition of sterile pyrogen-free water. The resulting aqueous intravenous solution may be safely administered to a mammal in need of nutrient therapy. The packaged nutrient compositions of the invention exhibit greatly extended storage life and provide an economical method of providing intravenous solutions which are safe and efficacious for use. (author)

  17. Efficacy and safety of intravenous fentanyl administered by ambulance personnel

    DEFF Research Database (Denmark)

    Friesgaard, Kristian Dahl; Nikolajsen, Lone; Giebner, Matthias

    2016-01-01

    BACKGROUND: Management of pain in the pre-hospital setting is often inadequate. In 2011, ambulance personnel were authorized to administer intravenous fentanyl in the Central Denmark Region. The aim of this study was to evaluate the efficacy and safety of intravenous fentanyl administered...... by ambulance personnel. METHODS: Pre-hospital medical charts from 2348 adults treated with intravenous fentanyl by ambulance personnel during a 6-month period were reviewed. The primary outcome was the change in pain intensity on a numeric rating scale (NRS) from before fentanyl treatment to hospital arrival...... patients (1.3%) and hypotension observed in 71 patients (3.0%). CONCLUSION: Intravenous fentanyl caused clinically meaningful pain reduction in most patients and was safe in the hands of ambulance personnel. Many patients had moderate to severe pain at hospital arrival. As the protocol allowed higher doses...

  18. Intravenous Carbamazepine for Adults With Seizures.

    Science.gov (United States)

    Vickery, P Brittany; Tillery, Erika E; DeFalco, Alicia Potter

    2018-03-01

    To review the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions, and place in therapy of the intravenous (IV) formulation of carbamazepine (Carnexiv) for the treatment of seizures in adult patients. A comprehensive PubMed and EBSCOhost search (1945 to August 2017) was performed utilizing the keywords carbamazepine, Carnexiv, carbamazepine intravenous, IV carbamazepine, seizures, epilepsy, and seizure disorder. Additional data were obtained from literature review citations, manufacturer's product labeling, and Lundbeck website as well as Clinicaltrials.gov and governmental sources. All English-language trials evaluating IV carbamazepine were analyzed for this review. IV carbamazepine is FDA approved as temporary replacement therapy for treatment of adult seizures. Based on a phase I trial and pooled data from 2 open-label bioavailability studies comparing oral with IV dosing, there was no noted indication of loss of seizure control in patients switched to short-term replacement antiepileptic drug therapy with IV carbamazepine. The recommended dose of IV carbamazepine is 70% of the patient's oral dose, given every 6 hours via 30-minute infusions. The adverse effect profile of IV carbamazepine is similar to that of the oral formulation, with the exception of added infusion-site reactions. IV carbamazepine is a reasonable option for adults with generalized tonic-clonic or focal seizures, previously stabilized on oral carbamazepine, who are unable to tolerate oral medications for up to 7 days. Unknown acquisition cost and lack of availability in the United States limit its use currently.

  19. Choice of intravenous contrast material for CT

    International Nuclear Information System (INIS)

    Cohen, M.D.; Herman, E.; Herron, D.; White, S.T.; Smith, J.A.; Cory, D.A.

    1989-01-01

    For CT, minor side effects (e.g., nausea, vomiting, pain) following intravenous administration of contrast medium may degrade image quality by causing patient motion or by delaying scanning. The objective of this study was to see if nonionic contrast agents offer advantages in reducing the incidence of such side effects. One hundred five pediatric patients randomly received iohexol (Omnipaque), Iopamidol (Isovue), or diatrizoate sodium (Hypaque). Contrast medium was given in doses of 2 mL/kg body weight (300 mg of iodine per milliliter). The results are presented in the paper

  20. Repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome undergoing In Vitro fertilization cycles provides a better cycle outcome - a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Krishna Deepika

    2017-01-01

    Full Text Available Objective: Is a single dose of gonadotropin-releasing hormone agonist (GnRHa trigger to induce final oocyte maturation in polycystic ovarian syndrome (PCOS undergoing in vitro fertilization (IVF cycles with GnRH antagonist protocol sufficient to provide optimal oocyte maturity? Design: This is a prospective, randomized, double-blind, proof-of-concept study. Setting: This study was carried out at a tertiary care center. Material and Methods: A total of 125 patients diagnosed with PCOS defined as per the ESHRE/ASRM Rotterdam criteria (2003 undergoing IVF in antagonist protocol were randomized into two groups. Group A: single dose of GnRHa 0.2 mg, 35 h prior to oocyte retrieval, and Group B: 0.2 mg GnRHa 35 h prior to oocyte retrieval + repeat dose of 0.1 mg 12 h following the 1st dose. 12 h post-trigger, luteinizing hormone (LH, progesterone (P4, and follicle-stimulating hormone (FSH values were estimated. Statistical Analysis: Continuous variables were expressed as mean ± standard deviation and categorical variables as proportions where applicable. Independent sample t-test was used for continuous variables which were normally distributed and Mann–Whitney U-test for data not normally distributed. Chi-square test or Fisher's exact test was used for categorical variables where appropriate. Odds ratio (OR with 95% confidence intervals (CIs was calculated. In addition, receiver operating characteristic curve was used to evaluate the post-trigger LH, P4, and FSH values at 12 h as predictors of oocyte maturity. Main Outcome Measures: Primary outcome: maturity rate of the oocytes. Secondary outcomes: oocyte yield, fertilization rate, availability of good quality embryos on day 3, blastocyst conversion, OHSS rates, post-trigger serum LH (IU/L, FSH (IU/L, and P4 (ng/mL levels implantation rate and clinical pregnancy rate. Results: A higher number of mature (metaphase II oocytes were obtained in Group B compared to Group A (OR of 0.47; CI: 0.38–0

  1. Successful outcome after intravenous gasoline injection.

    Science.gov (United States)

    Domej, Wolfgang; Mitterhammer, Heike; Stauber, Rudolf; Kaufmann, Peter; Smolle, Karl Heinz

    2007-12-01

    Gasoline, ingested intentionally or accidentally, is toxic. The majority of reported cases of gasoline intoxication involve oral ingestion or inhalation. Data are scarce on complications and outcomes following hydrocarbon poisoning by intravenous injection. Following a suicide attempt by intravenous self-injection of 10 ml of gasoline, a 26-year-old medical student was admitted to the intensive care unit (ICU) with hemoptysis, symptoms of acute respiratory failure, chest pain, and severe abdominal cramps. Gas exchange was severely impaired and a chest x-ray indicated chemical pneumonitis. Initial treatment consisted of mechanical ventilation, supportive hyperventilation, administration of nitrogen oxide (NO), and prednisone. Unfortunately, the patient developed multi-organ dysfunction syndrome (MODS) complicated by life-threatening severe vasoplegia within 24 hours after gasoline injection. High doses of vasopressors along with massive amounts of parenteral fluids were necessary. Despite fluid replacement, renal function worsened and required hemofiltration on 5 sequential days. After 12 days of intensive care management, the patient recovered completely and was discharged to a psychiatric care facility. Intravenous gasoline injection causes major injury to the lungs, the organ bearing the first capillary bed encountered. Treatment of gasoline poisoning is symptomatic because no specific antidote is available. Early and aggressive supportive care may be conducive to a favorable outcome with minimal residual pulmonary sequelae.

  2. The new generation of intravenous iron: chemistry, pharmacology, and toxicology of ferric carboxymaltose.

    Science.gov (United States)

    Funk, Felix; Ryle, Peter; Canclini, Camillo; Neiser, Susann; Geisser, Peter

    2010-01-01

    An ideal preparation for intravenous iron replacement therapy should balance effectiveness and safety. Compounds that release iron rapidly tend to cause toxicity, while large molecules can induce antibody formation and cause anaphylactic reactions. There is therefore a need for an intravenous iron preparation that delivers appropriate amounts of iron in a readily available form but with minimal side effects and thus with an excellent safety profile. In this paper, a review is given on the chemistry, pharmacology, and toxicology of ferric carboxymaltose (FCM, Ferinject), a stable and robust complex formulated as a colloidal solution with a physiological pH. The complex is gradually taken up mainly from the hepatic reticulo-endothelial system (RES), followed by effective delivery of iron to the endogeneous transport system for the haem synthesis in new erythrocytes, as shown in studies on the pharmacodynamics and pharmacokinetics with radio-labelled FCM. Studies with radio-labelled FCM also demonstrated a barrier function of the placenta and a low transfer of iron into the milk of lactating rats. Safety pharmacology studies indicated a favourable profile with regard to cardiovascular, central nervous, respiratory, and renal toxicity. A high maximum non-lethal dose was demonstrated in the single-dose toxicity studies. Furthermore, based on the No-Observed-Adverse-Effect-Levels (NOAELs) found in repeated-dose toxicity studies and on the cumulative doses administered, FCM has good safety margins. Reproductive and developmental toxicity studies did not reveal any direct or indirect harmful effects. No genotoxic potential was found in in vitro or in vivo studies. Moreover, antigenicity studies showed no cross-reactivity of FMC with anti-dextran antibodies and also suggested that FCM does not possess sensitizing potential. Lastly, no evidence of irritation was found in local tolerance studies with FCM. This excellent toxicity profile and the high effectiveness of FCM allow

  3. Ultrasonography versus intravenous urography

    International Nuclear Information System (INIS)

    Aslaksen, A.

    1991-01-01

    The present study was performed to compare the clinical value of urography and ultrasonography in a non-selected group of patients referred for urography to a university hospital. The conslusions and clinical implications of the study are as follows: Intravenous urography remains the cornerstone imaging examination in the evaluation of ureteral calculi. Ultrasonography is a valuable adjunct in cases of non- visualization of the kidneys, in distal obstruction and known contrast media allergy. When women with recurrent urinary tract infection are referred for imaging of the urinary tract, ultrasonography should be used. Ultrasonography should replace urography for screening of non-acute hydronephrosis like in female genital cancer and benign prostate hyperplasia. There is good correlation between urography and ultrasonography in assessing the degree of hydronephrosis. However, more researh on the relationship between hydronephrosis and obstruction is necessary. Ultrasonography should be used as the only imaging method of the upper urinary tract in patients with microscopic hematuria. In patients less than 50 years with macroscopic hematuria, ultrasonography should be used as the only imaging of the upper urinary tract, and an examination of the urinary bladder should be included. In patients over 50 years, urography supplied with ultrasonography should be used, but more research is necessary on the subject of imaging method and age. 158 refs

  4. Intravenous levetiracetam terminates refractory status epilepticus in two patients with migrating partial seizures in infancy.

    Science.gov (United States)

    Cilio, Maria Roberta; Bianchi, Roberto; Balestri, Martina; Onofri, Alfredo; Giovannini, Simona; Di Capua, Matteo; Vigevano, Federico

    2009-09-01

    To evaluate the efficacy and tolerability of intravenous (IV) levetiracetam in refractory status epilepticus of migrating partial seizures in infancy (MPSI). IV levetiracetam was infused in two infants, first as a loading dose of 60mg/kg in 30min, then at 30mg/kg twice a day. Both infants were continuously monitored with video-EEG before, during and after the drug trial. Blood count, liver enzymes, serum creatinine, ammonia and lactate blood levels were performed repeatedly before and after the IV levetiracetam administration. Follow-up was of 16 and 10 months. EEG monitoring allowed the diagnosis of MPSI, showing the typical seizures pattern in both patients. IV levetiracetam was effective in stopping status epilepticus in both infants. Levetiracetam also prevented the recurrence of status epilepticus during follow-up. No adverse reactions were observed during the infusion phase or during follow-up. MPSI is a newly recognized epileptic syndrome characterized by early onset of intractable partial seizures arisingly independently and sequentially from both hemispheres, migrating from one region of the brain to another and from one hemisphere to another. We report the efficacy of intravenous levetiracetam in resolving refractory status epilepticus in two infants with this new epilepsy syndrome.

  5. Recent results and future prospects of dynamic intravenous coronary angiography using synchrotron radiation

    International Nuclear Information System (INIS)

    Ohtsuka, Sadanori

    1999-01-01

    We have developed a dynamic intravenous coronary angiography (IVCAG) by using synchrotron radiation (SR) as a less invasive and more easy examination in place of CAG. Twelve patients suspected to have angina pectoris underwent IVCAG at the clinic in the National Laboratory for High Energy Accelerator Research Organization (KEK). The patients received an intravenous injection of 40m/of contrast agent, and then irradiation was performed with a wide (130 mm x 80 mm) and monochromatic (35 KeV) X-ray beam. Images were acquired with an image intensifier and recorded with a digital fluorography system as dynamic angiography at 30 or 10 images/sec. IVCAG was repeated in 2 or 3 projections. In all patients, the dynamic images permitted clear visualization of the coronary arteries and enabled evaluation of coronary anatomy. Two patients were diagnosed to have coronary stenosis by IVCAG and were confirmed by conventional CAG. The total irradiation doses used for IVCAG were less than those for conventional angiography. Although the image definition obtained with dynamic IVCAG was somewhat less than that of conventional CAG and needs to be improved, the IVCAG can be easily used for the evaluation of coronary arteries and may be clinically used for screening and follow-up of coronary artery disease. In future, the improvement of imaging system, such as increased intensity of synchrotron radiation and high sensitivity in imaging detector, will make more advance in image quality. (author)

  6. Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans

    DEFF Research Database (Denmark)

    Carl, Peder; Høgskilde, S; Lang-Jensen, T

    1994-01-01

    Eltanolone, a new intravenous steroid anaesthetic agent was administered intravenously in a dose of 0.6 mg.kg-1 over 45 s to eight healthy male volunteers to evaluate some of its pharmacokinetic and pharmacodynamic effects. Drug concentration-time data were analysed by PCNONLIN, a non...

  7. The analgesic efficacy of intravenous versus oral tramadol for preventing postoperative pain after third molar surgery

    NARCIS (Netherlands)

    Ong, Cliff K. S.; Lirk, Phillip; Tan, Juliana M. H.; Sow, Belle W. Y.

    2005-01-01

    The aim of this study was to compare the analgesic efficacy of single-dose preoperative intravenous versus oral tramadol for preventing pain after third molar surgery. Seventy-two patients undergoing elective third molar surgery were randomized to receive either intravenous (n = 36) or oral (n = 36)

  8. Contrast agent choice for intravenous coronary angiography

    International Nuclear Information System (INIS)

    Zeman, H.D.; Siddons, D.P.

    1990-01-01

    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation X-rays and an iodine-containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic X-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron radiation source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the X-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation X-rays is visualizing a coronary artery through the left ventricle or aorta which also contain contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth. The X-ray energy spectrum of the X-17 superconduction wiggler beam line at the National Synchrotron Light Source at Brookhaven National Laboratory has been used for these calculations. Both perfect Si crystals and Si crystals with a small mosaic spread are considered as monochromators. Contrast agents containing Gd or Yb seem to have about the optimal calculated signal to noise ratio. (orig./HSI)

  9. A Phase 1, Single-center, Double-blind, Placebo-controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Clinical Effects, and Pharmacokinetics-Pharmacodynamics of Intravenous Cyclopropyl-methoxycarbonylmetomidate (ABP-700) after a Single Ascending Bolus Dose.

    Science.gov (United States)

    Struys, Michel M R F; Valk, Beatrijs I; Eleveld, Douglas J; Absalom, Anthony R; Meyer, Peter; Meier, Sascha; den Daas, Izaak; Chou, Thomas; van Amsterdam, Kai; Campagna, Jason A; Sweeney, Steven P

    2017-07-01

    Cyclopropyl-methoxycarbonylmetomidate (ABP-700) is a new "soft" etomidate analog. The primary objectives of this first-in-human study were to describe the safety and efficacy of ABP-700 and to determine its maximum tolerated dose. Secondary objectives were to characterize the pharmacokinetics of ABP-700 and its primary metabolite (cyclopropyl-methoxycarbonyl acid), to assess the clinical effects of ABP-700, and to investigate the dose-response and pharmacokinetic/pharmacodynamic relationships. Sixty subjects were divided into 10 cohorts and received an increasing, single bolus of either ABP-700 or placebo. Safety was assessed by clinical laboratory evaluations, infusion-site reactions, continuous monitoring of vital signs, physical examination, adverse event monitoring, and adrenocorticotropic hormone stimulation testing. Clinical effects were assessed with modified observer's assessment of alertness/sedation and Bispectral Index monitoring. Pharmacokinetic parameters were calculated. Stopping criteria were met at 1.00 mg/kg dose. No serious adverse events were reported. Adverse events were dose-dependent and comprised involuntary muscle movement, tachycardia, and ventilatory effects. Adrenocorticotropic hormone stimulation evoked a physiologic cortisol response in all subjects, no different from placebo. Pharmacokinetics were dose-proportional. A three-compartment pharmacokinetic model described the data well. A rapid onset of anesthesia/sedation after bolus administration and also a rapid recovery were observed. A quantitative concentration-effect relationship was described for the modified observer's assessment of alertness/sedation and Bispectral Index. This first-in-human study of ABP-700 shows that ABP-700 was safe and well tolerated after single-bolus injections up to 1.00 mg/kg. Bolus doses of 0.25 and 0.35 mg/kg were found to provide the most beneficial clinical effect versus side-effect profile.

  10. Intravenous ferric carboxymaltose for anaemia in pregnancy.

    Science.gov (United States)

    Froessler, Bernd; Collingwood, Joshua; Hodyl, Nicolette A; Dekker, Gustaaf

    2014-03-25

    Iron deficiency is a common nutritional deficiency amongst women of childbearing age. Peri-partum iron deficiency anaemia (IDA) is associated with significant maternal, fetal and infant morbidity. Current options for treatment are limited: these include oral iron supplementation, which can be ineffective and poorly tolerated, and red blood cell transfusions, which carry an inherent risk and should be avoided. Ferric carboxymaltose is a new treatment option that may be better tolerated.The study was designed to assess the safety and efficacy of iron deficiency anaemia (IDA) correction with intravenous ferric carboxymaltose in pregnant women with mild, moderate and severe anaemia in the second and third trimester. Prospective observational study; 65 anaemic pregnant women received ferric carboxymaltose up to 15 mg/kg between 24 and 40 weeks of pregnancy (median 35 weeks gestational age, SD 3.6). Treatment effectiveness was assessed by repeat haemoglobin (Hb) measurements and patient report of well-being in the postpartum period. Safety was assessed by analysis of adverse drug reactions and fetal heart rate monitoring during the infusion. Intravenous ferric carboxymaltose infusion significantly increased Hb values (p anaemia in pregnancy.

  11. Pre-emptive analgesia using intravenous fentanyl plus low-dose ketamine for radical prostatectomy under general anesthesia does not produce short-term or long-term reductions in pain or analgesic use.

    NARCIS (Netherlands)

    Katz, J.; Schmid, R.L.; Snijdelaar, D.G.; Coderre, T.J.; McCartney, C.J.; Wowk, A.

    2004-01-01

    The aim of the study was to evaluate post-operative pain and analgesic use after pre-operative or post-incisional i.v. fentanyl plus low dose i.v. ketamine vs. a standard treatment receiving i.v. fentanyl but not ketamine. Men undergoing radical prostatectomy under general anesthesia were randomly

  12. Intravenous and Subcutaneous Toxicity and Absorption Kinetics in Mice and Dogs of the Antileishmanial Triterpene Saponin PX-6518

    Directory of Open Access Journals (Sweden)

    Louis Maes

    2013-04-01

    Full Text Available The intravenous (IV and subcutaneous (SC toxicity and absorption kinetics of the antileishmanial triterpene saponin PX-6518 and its active constituents maesabalide-III and -IV were studied in mice and dogs. A high-dose wash-out study of PX-6518 at 20 mg/kg SC for 5 days and a single low-dose wash-out study at 1, 2.5 or 5 mg/kg SC and IV with follow-up until day 35 after treatment were performed in mice. Beagle dogs received three escalating doses of maesabalide-III and -IV at weekly intervals (0.01, 0.1 and 0.5 mg/kg IV and maesabalide-III was also dosed SC at 0.1, 0.2 and 0.4 mg/kg. Endpoint measurements included clinical, hematological and serum biochemical parameters. Pathology and toxicokinetic studies were performed on the dogs. Whereas the neutrophils and aspartate aminotransferase and alanine aminotransferase levels were increased in the high-dose wash-out mouse study, these parameters did not change in the low-dose wash-out study. The dogs were far more susceptible than mice to liver toxicity (hepatocellular necrosis and elevated liver enzymes and developed a painful inflammatory reaction at the SC injection site. Toxicokinetic analysis revealed a non dose-linear systemic availability with plasma concentrations above the antileishmanial IC50 after only a single dose at 0.01 mg/kg IV or 0.1 mg/kg SC. Related to the long half-life (T1/2 71–91 h after SC dosing, repeated dosing at weekly intervals may result in drug accumulation and enhanced toxicity. It was decided not to pursue further drug development for PX-6518 because of the hepatotoxic risk.

  13. Systematic review of the use of intravenous amiodarone and nifekalant for cardiopulmonary resuscitation in Japan

    Directory of Open Access Journals (Sweden)

    Mari Amino, MD, PhD

    2014-06-01

    Conclusions: Amiodarone and nifekalant were equivalent in their prophylactic and defibrillation efficacy. Concerning the initial amiodarone dose, the 125 mg intravenous [i.v.] over 10 min seemed to be more appropriate for the Japanese population.

  14. The Value of Intravenous Prostaglandin E2 after Intra-uterine Death

    African Journals Online (AJOL)

    1974-09-21

    Sep 21, 1974 ... using different routes of administration of the prosta- glandin. Given by ..... The disadvantages of intravenous prostaglandins are the systemic ... advantage of this method is that labour can be accurately monitored and the dose ...

  15. Population pharmacokinetics of intravenous Erwinia asparaginase in pediatric acute lymphoblastic leukemia patients

    NARCIS (Netherlands)

    Sassen, Sebastiaan D. T.; Mathôt, Ron A. A.; Pieters, Rob; Kloos, Robin Q. H.; de Haas, Valérie; Kaspers, Gertjan J. L.; van den Bos, Cor; Tissing, Wim J. E.; te Loo, Maroeska; Bierings, Marc B.; Kollen, Wouter J. W.; Zwaan, Christian M.; van der Sluis, Inge M.

    2017-01-01

    Erwinia asparaginase is an important component in the treatment of pediatric acute lymphoblastic leukemia. A large variability in serum concentrations has been observed after intravenous Erwinia asparaginase. Currently, Dutch Childhood Oncology Group protocols dose alterations are based on trough

  16. Population pharmacokinetics of intravenous Erwinia asparaginase in pediatric acute lymphoblastic leukemia patients

    NARCIS (Netherlands)

    Sassen, Sebastiaan D. T.; Mathot, Ron A. A.; Pieters, Rob; Kloos, Robin Q. H.; de Haas, Valerie; Kaspers, Gertjan J. L.; van den Bos, Cor; Tissing, Wim J. E.; te Loo, D. Maroeska W. M.; Bierings, Marc B.; Kollen, Wouter J. W.; Zwaan, Christian M.; van der Sluis, Inge M.

    Erwinia asparaginase is an important component in the treatment of pediatric acute lymphoblastic leukemia. A large variability in serum concentrations has been observed after intravenous Erwinia asparaginase. Currently, Dutch Childhood Oncology Group protocols dose alterations are based on trough

  17. Comparison in the calculation of committed effective dose using the ICRP 30 and ICRP 60 models for a repeated incorporation by inhalation of I-125; Comparacion en el calculo de la dosis efectiva comprometida usando los modelos del ICRP 30 y del ICRP 60 para una incorporacion repetida por inhalacion de I-125

    Energy Technology Data Exchange (ETDEWEB)

    Carreno P, A.L.; Cortes C, A. [CNSNS, Dr. Barragan 779, Col. Narvarte, Mexico D.F. (Mexico); Alonso V, G.; Serrano P, F. [IPN, Edificio de Fisica Avanzada Zacatenco, 07300 Mexico D.F. (Mexico)

    2005-07-01

    Presently work, a comparison in the calculation of committed effective dose using the models of the ICRP 30 and those of the ICRP 60 for the analysis of internal dose due to repeated incorporation of I-125 is shown. The estimations of incorporated activity are obtained starting from the proportionate data for an exercise of inter comparison, with which it should be determined the internal dose later on. For to estimate the initial activity incorporated by repeated dose was assumed that this it was given through of multiple individual incorporations which happened in the middle points of the monitoring periods. The results using the models of the ICRP 30 and of the ICRP 60 are compared and the causes of the differences are analyzed. (Author)

  18. Errors in the administration of intravenous medication in Brazilian hospitals.

    Science.gov (United States)

    Anselmi, Maria Luiza; Peduzzi, Marina; Dos Santos, Claudia Benedita

    2007-10-01

    To verify the frequency of errors in the preparation and administration of intravenous medication in three Brazilian hospitals in the State of Bahia. The administration of intravenous medications constitutes a central activity in Brazilian nursing. Errors in performing this activity may result in irreparable damage to patients and may compromise the quality of care. Cross-sectional study, conducted in three hospitals in the State of Bahia, Brazil. Direct observation of the nursing staff (nurse technicians, auxiliary nurses and nurse attendants), preparing and administering intravenous medication. When preparing medication, wrong patient error did not occur in any of the three hospitals, whereas omission dose was the most frequent error in all study sites. When administering medication, the most frequent errors in the three hospitals were wrong dose and omission dose. The rates of error found are considered low compared with similar studies. The most frequent types of errors were wrong dose and omission dose. The hospitals studied showed different results with the smallest rates of errors occurring in hospital 1 that presented the best working conditions. Relevance to clinical practice. Studies such as this one have the potential to improve the quality of care.

  19. Concentrations in plasma, epithelial lining fluid, alveolar macrophages and bronchial mucosa after a single intravenous dose of 1.6 mg/kg of iclaprim (AR-100) in healthy men.

    Science.gov (United States)

    Andrews, J; Honeybourne, D; Ashby, J; Jevons, G; Fraise, A; Fry, P; Warrington, S; Hawser, S; Wise, R

    2007-09-01

    A validated microbiological assay was used to measure concentrations of iclaprim (AR-100) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF) after a single 1.6 mg/kg intravenous 60 min iv infusion of iclaprim. Male volunteers were randomly allocated to three nominal sampling time intervals 1-2 h (Group A), 3-4 h (Group B) and 5.5-7.0 h (Group C) after the start of the drug infusion. Mean iclaprim concentrations in plasma, BM, AM and ELF, respectively, were for Group A 0.59 mg/L (SD 0.18), 0.51 mg/kg (SD 0.17), 24.51 mg/L (SD 21.22) and 12.61 mg/L (SD 7.33); Group B 0.24 mg/L (SD 0.05), 0.35 mg/kg (SD 0.17), 7.16 mg/L (SD 1.91) and 6.38 mg/L (SD 5.17); and Group C 0.14 mg/L (SD 0.05), no detectable level in BM, 5.28 mg/L (SD 2.30) and 2.66 mg/L (SD 2.08). Iclaprim concentrations in ELF and AM exceeded the MIC(90) for penicillin-susceptible Streptococcus pneumoniae (MIC90 0.06 mg/L), penicillin-intermediate S. pneumoniae (MIC90 2 mg/L), penicillin-resistant S. pneumoniae (MIC90 4 mg/L) for 7, 7 and 4 h, respectively, and Chlamydia pneumoniae (MIC90 0.5 mg/L) for 7 h. Mean iclaprim concentrations in ELF exceeded the MIC90 for Haemophilus influenzae (MIC90 4 mg/L) and Moraxella catarrhalis (MIC90 8 mg/L) for up to 4 and 2 h, respectively; in AM the MIC90 was exceeded for up to 7 h. Furthermore, the MIC90 for methicillin-resistant Staphylococcus aureus of 0.12 mg/L was exceeded at all sites for up to 7 h. These data suggest that iclaprim reaches lung concentrations that should be effective in the treatment of community-acquired pneumonia.

  20. Orthostatic stability with intravenous levodopa

    Directory of Open Access Journals (Sweden)

    Shan H. Siddiqi

    2015-08-01

    Full Text Available Intravenous levodopa has been used in a multitude of research studies due to its more predictable pharmacokinetics compared to the oral form, which is used frequently as a treatment for Parkinson’s disease (PD. Levodopa is the precursor for dopamine, and intravenous dopamine would strongly affect vascular tone, but peripheral decarboxylase inhibitors are intended to block such effects. Pulse and blood pressure, with orthostatic changes, were recorded before and after intravenous levodopa or placebo—after oral carbidopa—in 13 adults with a chronic tic disorder and 16 tic-free adult control subjects. Levodopa caused no statistically or clinically significant changes in blood pressure or pulse. These data add to previous data that support the safety of i.v. levodopa when given with adequate peripheral inhibition of DOPA decarboxylase.

  1. Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

    Science.gov (United States)

    Elhennawy, Mai Gamal; Lin, Hai-Shu

    2018-06-15

    Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT 0→last ), higher dose-normalized maximal plasma concentration (C max /Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats

    Science.gov (United States)

    2014-01-01

    Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an

  3. Is There a Role for Intravenous Subdissociative-Dose Ketamine Administered as an Adjunct to Opioids or as a Single Agent for Acute Pain Management in the Emergency Department?

    Science.gov (United States)

    Motov, Sergey; Rosenbaum, Steven; Vilke, Gary M; Nakajima, Yuko

    2016-12-01

    Whether acute or chronic, emergency physicians frequently encounter patients reporting pain. It is the responsibility of the emergency physician to assess and evaluate, and if appropriate, safely and effectively reduce pain. Recently, analgesics other than opioids are being considered in an effort to provide safe alternatives for pain management in the emergency department (ED). Opioids have significant adverse effects such as respiratory depression, hypotension, and sedation, to say nothing of their potential for abuse. Although ketamine has long been used in the ED for procedural sedation and rapid sequence intubation, it is used infrequently for analgesia. Recent evidence suggests that ketamine use in subdissociative doses proves to be effective for pain control and serves as a feasible alternative to traditional opioids. This paper evaluates ketamine's analgesic effectiveness and safety in the ED. This is a literature review of randomized controlled trials, systematic reviews, meta-analyses, and observational studies evaluating ketamine for pain control in the ED setting. Based on these search parameters, eight studies were included in the final analysis and graded based on the American Academy of Emergency Medicine Clinical Practice Committee manuscript review process. A total of eight papers were reviewed in detail and graded. Recommendations were given based upon this review process. Subdissociative-dose ketamine (low-dose ketamine) is effective and safe to use alone or in combination with opioid analgesics for the treatment of acute pain in the ED. Its use is associated with higher rates of minor, but well-tolerated adverse side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Evaluation of the repeated-dose liver micronucleus assay using N-nitrosomorpholine in young adult rats: report on collaborative study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study (MMS) Group.

    Science.gov (United States)

    Hayashi, Aya; Kosaka, Mizuki; Kimura, Aoi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

    2015-03-01

    The present study was conducted to evaluate the suitability of a repeated-dose liver micronucleus (LMN) assay in young adult rats as a collaborative study by the Mammalian mutagenicity study (MMS) group. All procedures were performed in accordance with the standard protocols of the MMS Group. Six-week-old male Crl:CD(SD) rats (5 animals/group) received oral doses of the hepatocarcinogen N-nitrosomorpholine (NMOR) at 0 (control), 5, 10, and 30mg/kg/day (10mL/kg) for 14 days. Control animals received vehicle (water). Hepatocytes were collected from the liver 24h after the last dose, and the number of micronucleated hepatocytes (MNHEPs) was determined by microscopy. The number of micronucleated immature erythrocytes (MNIMEs) in the femoral bone marrow was also determined. The liver was examined using histopathologic methods after formalin fixation. The results showed statistically significant and dose-dependent increases in the number of MNHEPs in the liver at doses of 10mg/kg and greater when compared with the vehicle control. However, no significant increase was noted in the number of MNIMEs in the bone marrow at doses of up to 30mg/kg. Histopathology of the liver revealed hypertrophy and single cell necrosis of hepatocytes at doses of 5mg/kg and above. These results showed that the induction of micronuclei by NMOR was detected by the repeated-dose LMN assay, but not by the repeated-dose bone marrow micronucleus assay. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Intravenous immunoglobulin therapy and systemic lupus erythematosus.

    Science.gov (United States)

    Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

    2005-12-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

  6. Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous, subcutaneous and oral administration.

    Science.gov (United States)

    Kimble, B; Black, L A; Li, K M; Valtchev, P; Gilchrist, S; Gillett, A; Higgins, D P; Krockenberger, M B; Govendir, M

    2013-10-01

    The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz ) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss ) of 0.22 ± 0.12 L/kg. Median plasma terminal half-life (t(1/2)) was 1.19 h (range 0.71-1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C(max) 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4-8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate. © 2013 John Wiley & Sons Ltd.

  7. Solar urticaria successfully treated with intravenous immunoglobulin.

    LENUS (Irish Health Repository)

    Hughes, R

    2012-02-01

    Idiopathic solar urticaria (SU) is a rare, debilitating photodermatosis, which may be difficult to treat. First-line treatment with antihistamines is effective in mild cases, but remission after phototherapeutic induction of tolerance is often short-lived. Other treatment options include plasma exchange, photopheresis and cyclosporin. We present two cases of severe, idiopathic SU, which were resistant to conventional treatment. Both patients achieved remission after administration of intravenous immunoglobulin (IVIg) and have remained in remission at 13 months and 4 years, respectively. There are only two case reports of successful treatment of solar urticaria with IVIg. In our experience IVIg given at a total dose of 2 g\\/kg over several 5-day courses about a month apart is an effective treatment option for severe idiopathic SU. It is also generally safe, even if certainly subject to significant theoretical risks, such as induction of viral infection or anaphylaxis.

  8. intravenous infusion of chlorimipramine (anafranil)

    African Journals Online (AJOL)

    the already extensive outpatient facilities at Johannesburg. Hospital as well as the Tara Neuro-Psychiatric Hospital for long-term therapy. Technique of Chlorimipramine Infusion. Initially 1 ampoule of chlorimipramine 25 mg in 250 mg of 5°~ dextrose saline was administered intravenously at the rate of 60 drops per minute.

  9. Intravenous lignocaine infusion for intractable pain in Ewing's sarcoma

    Directory of Open Access Journals (Sweden)

    Nivedita Page

    2018-01-01

    Full Text Available A 23-year-old female presented to our palliative care center with Ewing's sarcoma of the humerus with lung metastases. Pain in her arm was unrelieved by nonsteroidal anti-inflammatory drugs, neuropathic medication as well as morphine. She could not tolerate any further increase in opioid dose but was so distraught due to the pain that she wanted to die. An intravenous lignocaine infusion in a dose of 2 mg/kg was given over an hour for three successive days. This successfully relieved her pain after which she was settled with her original medication. We feel that in palliative care settings, where intractable pain and tolerance to morphine are so common, intravenous lignocaine infusions could provide a safe and effective tool for pain relief.

  10. CHARACTERIZATION OF AN INTRAVENOUS LIPOPOLYSACCHARIDE INFLAMMATION MODEL IN BROILER CHICKENS

    OpenAIRE

    De Boever , Sandra; Croubels , Siska; Meyer , Evelyne; Sys , Stanislas; Beyaert , Rudi; Ducatelle , Richard; De Backer , Patrick

    2009-01-01

    Abstract Intravenous administration of lipopolysaccharide (LPS) from Escherichia coli O127:B8 at a dose of 1,500,000 units/kg BW evoked a hypothermic response followed by a fever phase in five week old broiler chickens. The hypothermic phase coincided with a severe decrease in blood pressure. We assume that this decrease in blood pressure is, at least partly, responsible for the hypothermic phase of the body temperature curve. LPS administration also caused a decrease in circulatin...

  11. Intravenous Therapy: Hazards, Complications and Their Prevention ...

    African Journals Online (AJOL)

    Breaks in aseptic techniques, faulty handling of parenteral fluid containers, failure to discard out-dated intravenous solutions and tubings contribute to occurrence of intravenous-associated sepsis. Improper technique and lack of pharmaceutical knowledge when adding drugs into intravenous fluids contribute to ...

  12. Are intravenous injections of contrast media really less nephrotoxic than intra-arterial injections?

    Energy Technology Data Exchange (ETDEWEB)

    Nyman, Ulf [University of Lund, Department of Diagnostic Radiology, Trelleborg (Sweden); Almen, Torsten [Skaane University Hospital, Department of Clinical Sciences/Medical Radiology, University of Lund, Malmoe (Sweden); Jacobsson, Bo [University of Gothenburg and the Sahlgrenska Academy, Department of Diagnostic Radiology, The Queen Silvia Children' s Hospital, Goeteborg (Sweden); Aspelin, Peter [Karolinska Institute and University Hospital, Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm (Sweden)

    2012-06-15

    We oppose the opinion that the intra-arterial administration of iodine-based contrast media (CM) appears to pose a greater risk of contrast medium-induced nephropathy (CIN) than intravenous administration since (1) in intra-arterial coronary procedures and most other intra-arterial angiographic examinations, CM injections are also intravenous relative to the kidneys, (2) there is a lack of comparative trials studying the risk of CIN between intra-arterial and intravenous procedures with matched risk factors and CM doses, (3) a bias selection of patients with fewer risk factors may explain the seemingly lower rate of CIN after CT in comparison with coronary interventions, (4) the rate of CIN following intra-arterial coronary procedures may also be exaggerated owing to other causes of acute kidney failure, such as haemodynamic instability and microembolisation, (5) roughly the same gram-iodine/GFR ratio ({approx}1:1) as a limit of relatively safe CM doses has preliminarily been found for both intravenous CT and intra-arterial coronary procedures and (6) the substantially higher injected intravenous CM dose rate during CT relative to an intra-arterial coronary procedure might actually pose a higher risk of CIN following CT. Key Points circle Most intra-arterial injections of contrast media are intravenous relative to the kidneys. circle No evidence that intravenous CM injections should be less nephrotoxic than intra-arterial. circle Considerably higher dose rates of CM are used for CT relative to intra-arterial procedures. circle Higher dose rates may pose higher nephrotoxic risk for intravenous based CT studies. (orig.)

  13. Paediatric dose display

    International Nuclear Information System (INIS)

    Griffin, D.W.; Derges, S.; Hesslewood, S.

    1984-01-01

    A compact, inexpensive unit, based on an 8085 microprocessor, has been designed for calculating doses of intravenous radioactive injections for children. It has been used successfully for over a year. The dose is calculated from the body surface area and the result displayed in MBq. The operator can obtain the required dose on a twelve character alphanumeric display by entering the age of the patient and the adult dose using a hexadecimal keyboard. Circuit description, memory map and input/output, and firmware are dealt with. (U.K.)

  14. Intravenous Antiepileptic Drugs in Russia

    Directory of Open Access Journals (Sweden)

    P. N. Vlasov

    2014-01-01

    Full Text Available Launching four intravenous antiepileptic drugs: valproate (Depakene and Convulex, lacosamide (Vimpat, and levetiracetam (Keppra – into the Russian market has significantly broadened the possibilities of rendering care to patients in seizure emergency situations. The chemi- cal structure, mechanisms of action, indications/contraindications, clinical effectiveness and tolerability, advantages/disadvantages, and adverse events of using these drugs in urgent and elective neurology are discussed. 

  15. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    International Nuclear Information System (INIS)

    Aubuchon, Adam C.; Chan, Michael D.; Lovato, James F.; Balamucki, Christopher J.; Ellis, Thomas L.; Tatter, Stephen B.; McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G.

    2011-01-01

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80–90). The mean retreatment dose was 84.4 Gy (range, 60–90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  16. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  17. Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

    Directory of Open Access Journals (Sweden)

    Jiaying Xu

    Full Text Available BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂ nanoparticles (NPs are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg. Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. RESULTS: Death of mice in the highest dose (1387 mg/kg group was observed at day two after TiO₂ NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW coefficients, and lower liver and kidney coefficients in the TiO₂ NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO₂ NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO₂ NPs treated mice. CONCLUSIONS: Intravenous injection of TiO₂ NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.

  18. Conversion from intravenous to oral medications: assessment of a computerized intervention for hospitalized patients.

    Science.gov (United States)

    Fischer, Michael A; Solomon, Daniel H; Teich, Jonathan M; Avorn, Jerry

    2003-11-24

    Many hospitalized patients continue to receive intravenous medications longer than necessary. Earlier conversion from the intravenous to the oral route could increase patient safety and comfort, reduce costs, and facilitate earlier discharge from the hospital without compromising clinical care. We examined the effect of a computer-based intervention to prompt physicians to switch appropriate patients from intravenous to oral medications. This study was performed at Brigham and Women's Hospital, an academic tertiary care hospital at which all medications are ordered online. We targeted 5 medications with equal oral and intravenous bioavailability: fluconazole, levofloxacin, metronidazole, ranitidine, and amiodarone. We used the hospital's computerized order entry system to prompt physicians to convert appropriate intravenous medications to the oral route. We measured the total use of the targeted medications via each route in the 4 months before and after the implementation of the intervention. We also measured the rate at which physicians responded to the intervention when prompted. The average intravenous defined daily dose declined by 11.1% (P =.002) from the preintervention to the postintervention period, while the average oral defined daily dose increased by 3.7% (P =.002). Length of stay, case-mix index, and total drug use at the hospital increased during the study period. The average total monthly use of the intravenous preparation of all of the targeted medications declined in the 4 months after the intervention began, compared with the 4 months before. In 35.6% of 1045 orders for which a prompt was generated, the physician either made a conversion from the intravenous to the oral version or canceled the order altogether. Computer-generated reminders can produce a substantial reduction in excessive use of targeted intravenous medications. As online prescribing becomes more common, this approach can be used to reduce excess use of intravenous medications

  19. Renal function in patients with non-dialysis chronic kidney disease receiving intravenous ferric carboxymaltose

    DEFF Research Database (Denmark)

    Macdougall, Iain C; Bock, Andreas H; Carrera, Fernando

    2017-01-01

    BACKGROUND: Preclinical studies demonstrate renal proximal tubular injury after administration of some intravenous iron preparations but clinical data on renal effects of intravenous iron are sparse. METHODS: FIND-CKD was a 56-week, randomized, open-label, multicenter study in which patients...... with non-dialysis dependent chronic kidney disease (ND-CKD), anemia and iron deficiency without erythropoiesis-stimulating agent therapy received intravenous ferric carboxymaltose (FCM), targeting either higher (400-600 μg/L) or lower (100-200 μg/L) ferritin values, or oral iron. RESULTS: Mean (SD) e...... quartiles of FCM dose, change in ferritin or change in TSAT versus change in eGFR. Dialysis initiation was similar between groups. Renal adverse events were rare, with no indication of between-group differences. CONCLUSION: Intravenous FCM at doses that maintained ferritin levels of 100-200 μg/L or 400...

  20. The Value of Intravenous Prostaglandin E2 after Intra-uterine Death

    African Journals Online (AJOL)

    1974-09-21

    Sep 21, 1974 ... ficantly smaller doses of prostaglandins can achieve deli- very of the fetus and an intravenous route will be the method of choice. However, in cases of rhesus iso- immunisation, where larger doses of prostaglandin are required, with correspondingly more severe side-effects, the extra-amniotic route may be ...

  1. 1-3-7 minute intravenous urography

    International Nuclear Information System (INIS)

    Bahk, Yong Whee; Yoon, Sei Chul; Lee, Myung Hee

    1980-01-01

    Intravenous urography (IVU) as it is used widely today was probably started in early 1950's after the introduction of triiodobenzoic acid compounds as contrast media. This long cherished traditional method consists of taking radiograms at 5, 15 and 25 minutes after the injection of contrast medium. There are a few modifications of this standard urographic examination such as five minute IVU (Woodruff, 1959), minute-sequence pyelogram (Maxwell et al., 1964), drip infusion pyelography (Schencker, 1964) and nephrotomography (Evans et al., 1955). The present study has been undertaken to test if the conventional standard IVU can be more rapidly performed without losing essential informational contents of urograms. In this new clinical trial, urograms were taken at the end of 1, 3 and 7 minutes instead of 5, 15 and 25 minutes after the intravenous injection of contrast medium. We injected 40 ml of meglumine diatrizoate solution within 30 seconds using an 18G iv needle. (The amount of injected contrast medium has been reduced recently to ordinary single dose of 20 ml for subjects weighing less than 8 kg). Upon viewing the 7 minute film in front of an automatic processor, the examination was terminated after obtaining an upright view unless any further radiogram was indicated. As shown in Tables and Figures, our new 1-3-7 minute method has been proven to provide us with as much essential and useful information as conventional 5-15-25 minute urography. Thus, we were able to finish one examination within 10 minutes without losing any necessary diagnostic information. In some of patients with obstructive uropathy such as stone the examination was extended as long as it was desired. Side reactions were occasional nausea, flushing and rare mild vomiting which never prevented the examination

  2. Evaluation the effects of adding ketamine to morphine in intravenous patient-controlled analgesia after orthopedic surgery

    Directory of Open Access Journals (Sweden)

    Godrat Akhavanakbari

    2014-01-01

    Full Text Available Background: Intravenous patient-controlled analgesia (PCA with morphine is commonly used for post-operative pain after major surgery. Ketamine has analgesic property at lower doses, and in combination with opioids it could have synergistic effect. The aim of this study is to determine effects of the addition of ketamine to morphine for PCA after orthopedic surgery. Materials and Methods: In this double-blind randomized clinical trial, 60 patients were randomly allocated to receive PCA consisting: Group 1 (morphine 0.2 mg/ml, Group 2 (morphine 0.2 mg/ml + ketamine 1 mg/ml, and Group 3 (morphine 0.1 mg/ml + ketamine 2 mg/ml. In this, anesthesiologists managed study, patients had orthopedic surgery. Assessments were made at 24 h and 48 h post-operatively. Visual analog scale (VAS was used for recording pain score. PCA morphine use was recorded at 24 h and 48 h. VAS scores over 48 h were analyzed with analysis of variance for repeated measures. Significance level was taken as 0.05. Results: There is no significant difference between demographic information of the three groups ( P > 0.05. Control of pain in Group 2 and Group 3 was better than in Group 1 (only morphine ( P = 0.001 but there was no significant difference between Group 2 and Group 3 ( P > 0.05. Rate of narcotic consumption in groups 2 and 3 was significantly lower than Group 1 ( P < 0.05. Conclusion: After orthopedic surgery, the addition of ketamine to morphine for intravenous PCA was superior to Intravenous PCA opioid alone. The combination induces a significant reduction in pain score and cumulative morphine consumption.

  3. MYCOTIC FEMORAL PSEUDOANEURYSMS FROM INTRAVENOUS DRUG ABUSE

    Directory of Open Access Journals (Sweden)

    Vojko Flis

    2004-04-01

    Full Text Available Background. Parenteral drug abuse is the most common cause of infected femoral artery pseudoaneurysms (IFAP. This complication of intravenous drug abuse is not only limb threatening but can also be life threatening. The management of the IFAP is difficult and controversial. Generally speaking, ligation and excision of the pseudoaneurysm without revascularization is accepted procedure in majority of the patients. However it is not regarded as an appropriate procedure for cases where the high probability of amputation is expected from acute interruption of the femoral artery flow.Patients, methods and results. We present three cases of young (average 20 years, range 18–24 patients with IFAP, in which a primary reconstruction was performed due to absence of doppler signal over pedal arteries after ligation of common femoral artery. In two of them complications in form of haemorrhage and repeated infection developed in late postoperative period. The first one, had an excision and ligation while the second one had a reconstruction made by means of a silver impregnated dacron prosthesis. None of the patients required an amputation.Conclusions. Overall prognosis and prognosis of the reconstruction in parenteral drug abuse patients is uncertain because there is a high incidence of postoperative drug injection despite aggressive drug rehabilitation.

  4. A Lack of Systemic Absorption Following the Repeated Application of Topical Quetiapine in Healthy Adults.

    Science.gov (United States)

    Kayhart, Bryce; Lapid, Maria I; Nelson, Sarah; Cunningham, Julie L; Thompson, Virginia H; Leung, Jonathan G

    2018-01-01

    In the absence of suitable oral or intravenous access for medication administration and when the intramuscular medications are undesirable, alternative routes for drug delivery may be considered. Antipsychotics administered via an inhaled, intranasal, rectal, or topical route have been described in the literature. Topically administered antipsychotics have been previously reported to produce negligible systemic absorption despite being used in clinical practice for nausea and behavioral symptoms associated with dementia. Additionally, the American Academy of Hospice and Palliative Medicine recommends against the use of topical medications that lack supporting literature. Three studies have assessed the systemic absorption of different antipsychotics after administration of only a single, topically applied dose. To evaluate whether the repeated administration of a topically applied antipsychotic may result in detectable serum levels in an accumulating fashion, a pharmacokinetic study was conducted. Five healthy, adult participants consented to receive extemporaneously prepared topical quetiapine in Lipoderm every 4 hours for a total of 5 doses. Blood samples were drawn at baseline and hours 2, 4, 8, 12, 16, and 24, and serum quetiapine concentrations were measured using high-performance liquid chromatography. Quetiapine was undetectable in every sample from 3 participants. Two participants had minimally detectable serum quetiapine levels no sooner than hour 12 of the study period. Extemporaneously prepared quetiapine in Lipoderm resulted in nonexistent or minimal serum level following repeated topical administration. The use of topically applied quetiapine should still be questioned.

  5. Intravenous cobinamide versus hydroxocobalamin for acute treatment of severe cyanide poisoning in a swine (Sus scrofa) model.

    Science.gov (United States)

    Bebarta, Vikhyat S; Tanen, David A; Boudreau, Susan; Castaneda, Maria; Zarzabal, Lee A; Vargas, Toni; Boss, Gerry R

    2014-12-01

    Hydroxocobalamin is a Food and Drug Administration-approved antidote for cyanide poisoning. Cobinamide is a potential antidote that contains 2 cyanide-binding sites. To our knowledge, no study has directly compared hydroxocobalamin with cobinamide in a severe, cyanide-toxic large-animal model. Our objective is to compare the time to return of spontaneous breathing in swine with acute cyanide-induced apnea treated with intravenous hydroxocobalamin, intravenous cobinamide, or saline solution (control). Thirty-three swine (45 to 55 kg) were intubated, anesthetized, and instrumented (continuous mean arterial pressure and cardiac output monitoring). Anesthesia was adjusted to allow spontaneous breathing with FiO2 of 21% during the experiment. Cyanide was continuously infused intravenously until apnea occurred and lasted for 1 minute (time zero). Animals were then randomly assigned to receive intravenous hydroxocobalamin (65 mg/kg), cobinamide (12.5 mg/kg), or saline solution and monitored for 60 minutes. A sample size of 11 animals per group was selected according to obtaining a power of 80%, an α of .05, and an SD of 0.17 in mean time to detect a 20% difference in time to spontaneous breathing. We assessed differences in time to death among groups, using Kaplan-Meier estimation methods, and compared serum lactate, blood pH, cardiac output, mean arterial pressure, respiratory rate, and minute ventilation time curves with repeated-measures ANOVA. Baseline weights and vital signs were similar among groups. The time to apnea and cyanide dose required to achieve apnea were similar. At time zero, mean cyanide blood and lactate concentrations and reduction in mean arterial pressure from baseline were similar. In the saline solution group, 2 of 11 animals survived compared with 10 of 11 in the hydroxocobalamin and cobinamide groups (Pcyanide concentrations became undetectable at the end of the study in both antidote-treated groups, and no statistically significant differences

  6. Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.

    Science.gov (United States)

    van der Westhuizen, J; Kuo, P Y; Reed, P W; Holder, K

    2011-03-01

    Gastric absorption of oral paracetamol (acetaminophen) may be unreliable perioperatively in the starved and stressed patient. We compared plasma concentrations of parenteral paracetamol given preoperatively and oral paracetamol when given as premedication. Patients scheduled for elective ear; nose and throat surgery or orthopaedic surgery were randomised to receive either oral or intravenous paracetamol as preoperative medication. The oral dose was given 30 minutes before induction of anaesthesia and the intravenous dose given pre-induction. All patients were given a standardised anaesthetic by the same specialist anaesthetist who took blood for paracetamol concentrations 30 minutes after the first dose and then at 30 minute intervals for 240 minutes. Therapeutic concentrations of paracetamol were reached in 96% of patients who had received the drug parenterally, and 67% of patients who had received it orally. Maximum median plasma concentrations were 19 mg.l(-1) (interquartile range 15 to 23 mg.l(-1)) and 13 mg.l(-1) (interquartile range 0 to 18 mg.l(-1)) for the intravenous and oral group respectively. The difference between intravenous and oral groups was less marked after 150 minutes but the intravenous preparation gave higher plasma concentrations throughout the study period. It can be concluded that paracetamol gives more reliable therapeutic plasma concentrations when given intravenously.

  7. Oral ftorafur versus intravenous 5-fluorouracil. A comparative study in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Andersen, E; Pedersen, H

    1987-01-01

    The toxicities of oral Ftorafur (1 g/m2/day 1-21) and intravenous 5-fluorouracil (5-FU) (500 mg/m2/day 1-5) were compared in a prospective randomized study in patients with colorectal cancer. The treatment courses were repeated every 6th week. Leucopenia was more common after 5-FU. Leucocyte nadir...

  8. [Study of personal best value of peak expiratory flow in patients with asthma--comparison of the highest value of daily PEF under good control and the highest value of daily PEF obtained after using repeated inhaled beta2-agonist during high-dose inhaled steroid treatment].

    Science.gov (United States)

    Watanabe, Naoto; Makino, Sohei; Kihara, Norio; Fukuda, Takeshi

    2008-12-01

    In the guideline for asthma management, it is important to find the personal best value of peak expiratory flow (best PEF). Recently, we have substituted the highest value of PEF in daily life under good control (daily highest PEF) for the best PEF. In the present study, we considered whether the daily highest PEF could be used as the best PEF or not. Subjects were 30 asthmatics who were well controlled but whose baseline PEF values were less than 80 percent of predicted values. We compared the daily highest PEF and the highest of PEF obtained after repeated inhaled beta2-agonist (salbutamol MDI every 20 minutes three times). All subjects then received 1600 microg/day of beclomethasone dipropionate (BDP) for 4 to 8 weeks. We studied the effect of high-dose inhaled steroid treatment on each PEF value and compared the daily highest PEF and the highest PEF obtained after using repeated salbutamol MDI during high dose inhaled steroid therapy on the examination day again. The baseline PEF, daily highest PEF and the highest PEF obtained after salbutamol MDI were significantly less than the each values obtained after high-dose BDP. The best PEF value of them was the value obtained after repeated salbutamol MDI during high dose BDP. We suggest that the daily highest PEF under good control is not a substitute for best PEF because it changes according to the degree of improvement of airway inflammation. We recommend that a course of high dose inhaled steroid is effective in finding the best value of PEF for each individual with moderate asthma.

  9. Conscious sedation procedures using intravenous midazolam for dental care in patients with different cognitive profiles: a prospective study of effectiveness and safety.

    Directory of Open Access Journals (Sweden)

    Valérie Collado

    Full Text Available The use of midazolam for dental care in patients with intellectual disability is poorly documented. This study aimed to evaluate the effectiveness and safety of conscious sedation procedures using intravenous midazolam in adults and children with intellectual disability (ID compared to dentally anxious patients (DA. Ninety-eight patients with ID and 44 patients with DA programmed for intravenous midazolam participated in the study over 187 and 133 sessions, respectively. Evaluation criteria were success of dental treatment, cooperation level (modified Venham scale, and occurrence of adverse effects. The mean intravenous dose administered was 8.8±4.9 mg and 9.8±4.1 mg in ID and DA sessions respectively (t-test, NS. 50% N₂O/O₂ was administered during cannulation in 51% of ID sessions and 61% of DA sessions (NS, Fisher exact test. Oral or rectal midazolam premedication was administered for cannulation in 31% of ID sessions and 3% of DA sessions (p<0,001, Fisher exact test. Dental treatment was successful in 9 out of 10 sessions for both groups. Minor adverse effects occurred in 16.6% and 6.8% of ID and DA sessions respectively (p = 0.01, Fisher exact test. Patients with ID were more often very disturbed during cannulation (25.4% ID vs. 3.9% DA sessions and were less often relaxed after induction (58.9% ID vs. 90.3% DA and during dental treatment (39.5% ID vs. 59.7% DA (p<0.001, Fisher exact test than patients with DA. When midazolam sedation was repeated, cooperation improved for both groups. Conscious sedation procedures using intravenous midazolam, with or without premedication and/or inhalation sedation (50% N₂O/O₂, were shown to be safe and effective in patients with intellectual disability when administered by dentists.

  10. Feasibility of using intravenous contrast-enhanced computed tomography (CT) scans in lung cancer treatment planning

    International Nuclear Information System (INIS)

    Xiao Jianghong; Zhang Hong; Gong Youling; Fu Yuchuan; Tang Bin; Wang Shichao; Jiang Qingfeng; Li Ping

    2010-01-01

    Background and purpose: To investigate the feasibility of using intravenous contrast-enhanced computed tomography (CT) scans in 3-dimensional conformal radiotherapy (3D-CRT), stereotactic body radiation therapy (SBRT) and intensity-modulated radiotherapy (IMRT) treatment planning for lung cancers, respectively. Materials and methods: Twelve patients with bulky lung tumors and 14 patients with small lung tumors were retrospectively analyzed. Each patient took two sets of CT in the same position with active breathing control (ABC) technique before and after intravenous contrast agent (CA) injections. Bulky tumors were planned with 3D-CRT, while SBRT plans were generated for patients with small tumors based on CT scans with intravenous CA. In addition, IMRT plans were generated for patients with bulky tumors to continue on a planning study. All plans were copied and replaced on the scans without intravenous CA. The radiation doses calculated from the two sets of CTs were compared with regard to planning volumes (PTV), the organ at-risk (OAR) and the lungs using Wilcoxon's signed rank test. Results: In comparisons for 3D-CRT plans, CT scans with intravenous CA reduced the mean dose and the maximum dose of PTV with significant differences (p 95 ) for targets, respectively (p < 0.05). There was no statistical significance for lung parameters between two sets of scans in SBRT plans and IMRT plans. Conclusions: The enhanced CT scans can be used for both target delineation and treatment planning in 3D-CRT. The dose difference caused by intravenous CA is small. But for SBRT and IMRT, the minimum irradiation dose in targets may be estimated to be increased up to 2.71% while the maximum dose may be estimated to be decreased up to 1.36%. However, the difference in dose distribution in most cases were found to be clinical tolerable.

  11. High dose intravenous immunoglobulin in Rh and ABO hemolytic ...

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 12, No 1 (2014) >. Log in or Register to get access to full text downloads.

  12. High dose intravenous immunoglobulin in Rh and ABO hemolytic ...

    African Journals Online (AJOL)

    Ehab

    suggested as an alternative therapy to ET for rhesus. HDN.11-13 ... (HD-IVIG) in reducing the need for exchange transfusion, duration of phototherapy and/or hospitalization in ... blood group A and 34 neonates with blood group B, distributed ...

  13. Effectiveness of intravenous levetiracetam as an adjunctive treatment in pediatric refractory status epilepticus.

    Science.gov (United States)

    Kim, Jon Soo; Lee, Jeong Ho; Ryu, Hye Won; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Kim, Hunmin

    2014-08-01

    Intravenous levetiracetam (LEV) has been shown to be effective and safe in treating adults with refractory status epilepticus (SE). We sought to investigate the efficacy and safety of intravenous LEV for pediatric patients with refractory SE. We performed a retrospective medical-record review of pediatric patients who were treated with intravenous LEV for refractory SE. Clinical information regarding age, sex, seizure type, and underlying neurological status was collected. We evaluated other anticonvulsants that were used prior to administration of intravenous LEV and assessed loading dose, response to treatment, and any adverse events from intravenous LEV administration. Fourteen patients (8 boys and 6 girls) received intravenous LEV for the treatment of refractory SE. The mean age of the patients was 4.4 ± 5.5 years (range, 4 days to 14.6 years). Ten of the patients were neurologically healthy prior to the refractory SE, and the other 4 had been previously diagnosed with epilepsy. The mean loading dose of intravenous LEV was 26 ± 4.6 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 6 (43%) of the 14 patients. In particular, 4 (57%) of the 7 patients younger than 2 years showed seizure termination. No immediate adverse events occurred during or after infusions. The current study demonstrated that the adjunctive use of intravenous LEV was effective and well tolerated in pediatric patients with refractory SE, even in patients younger than 2 years. Intravenous LEV should be considered as an effective and safe treatment option for refractory SE in pediatric patients.

  14. Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors.

    Science.gov (United States)

    Lai, Pauline Siew Mei; Wong, Yin Yen; Low, Yong Chia; Lau, Hui Ling; Chin, Kin-Fah; Mahadeva, Sanjiv

    2014-01-01

    Background. Proton pump inhibitors (PPIs) are currently the most effective agents for acid-related disorders. However, studies show that 25-75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing. Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution. Setting. Prospective audit in a tertiary hospital in Malaysia. Method. Every 4th intravenous PPI prescription received in the pharmacy was screened against hospital guidelines. Interventions for incorrect indication/dose/duration were performed. Patients' demographic data, medical history and the use of intravenous PPI were collected. Included were all adult inpatients prescribed intravenous PPI. Main Outcome Measure. Proportion of appropriate IV PPI prescriptions. Results. Data for 106 patients were collected. Most patients were male [65(61.3%)], Chinese [50(47.2%)], with mean age ± SD = 60.3 ± 18.0 years. Most intravenous PPI prescriptions were initiated by junior doctors from the surgical [47(44.3%)] and medical [42(39.6%)] departments. Only 50/106(47.2%) patients had upper gastrointestinal endoscopy/surgery performed to verify the source of bleeding. Unexplained abdominal pain [81(76.4%)] was the main driver for prescribing intravenous PPIs empirically, out of which 73(68.9%) were for suspected upper gastrointestinal bleed. Overall, intravenous PPI was found to be inappropriately prescribed in 56(52.8%) patients for indication, dose or duration. Interventions on the use of intravenous PPI were most effective when performed by senior doctors (100%), followed by clinical pharmacists (50%), and inpatient pharmacists (37.5%, p = 0.027). Conclusion. Inappropriate intravenous PPI usage is still prevalent despite the enforcement of hospital guidelines. The promotion of prescribing awareness and evidence-based prescribing

  15. Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors

    Directory of Open Access Journals (Sweden)

    Pauline Siew Mei Lai

    2014-06-01

    Full Text Available Background. Proton pump inhibitors (PPIs are currently the most effective agents for acid-related disorders. However, studies show that 25–75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing.Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution.Setting. Prospective audit in a tertiary hospital in Malaysia.Method. Every 4th intravenous PPI prescription received in the pharmacy was screened against hospital guidelines. Interventions for incorrect indication/dose/duration were performed. Patients’ demographic data, medical history and the use of intravenous PPI were collected. Included were all adult inpatients prescribed intravenous PPI.Main Outcome Measure. Proportion of appropriate IV PPI prescriptions.Results. Data for 106 patients were collected. Most patients were male [65(61.3%], Chinese [50(47.2%], with mean age ± SD = 60.3 ± 18.0 years. Most intravenous PPI prescriptions were initiated by junior doctors from the surgical [47(44.3%] and medical [42(39.6%] departments. Only 50/106(47.2% patients had upper gastrointestinal endoscopy/surgery performed to verify the source of bleeding. Unexplained abdominal pain [81(76.4%] was the main driver for prescribing intravenous PPIs empirically, out of which 73(68.9% were for suspected upper gastrointestinal bleed. Overall, intravenous PPI was found to be inappropriately prescribed in 56(52.8% patients for indication, dose or duration. Interventions on the use of intravenous PPI were most effective when performed by senior doctors (100%, followed by clinical pharmacists (50%, and inpatient pharmacists (37.5%, p = 0.027.Conclusion. Inappropriate intravenous PPI usage is still prevalent despite the enforcement of hospital guidelines. The promotion of prescribing awareness and evidence

  16. INTRAVENOUS IMMUNOGLOBULIN IN PEDIATRIC RHEUMATOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    E. I. Alexeeva

    2015-01-01

    Full Text Available Modern successful treatment of rheumatic diseases is impossible without the use of intravenous immunoglobulin. The use of intravenous immunoglobulin is based on strict indications developed as a result of long-term multicenter controlled studies. The article highlights the issues of using immunoglobulin in pediatric rheumatology practice, and provides the review of literature with the results from the evaluation of the efficiency of intravenous immunoglobulin confirming the efficiency of the drug only for certain rheumatic diseases. 

  17. Effects of Intrarenal and Intravenous Infusion of the Phosphodiesterase 3 Inhibitor Milrinone on Renin Secretion

    Science.gov (United States)

    Kumagai, Kazuhiro; Reid, Ian A.

    1994-01-01

    We have reported that administration of the phosphodiesterase III inhibitor milrinone increases renin secretion in conscious rabbits. The aim of the present study was to determine if the increase in renin secretion results from a direct renal action of milrinone, or from an indirect extrarenal effect of the drug. This was accomplished by comparing the effects of intrarenal and intravenous infusion of graded doses of milrinone on plasma renin activity in unilaterally nephrectomized conscious rabbits. Milrinone was infused into the renal artery in doses of 0.01, 0.1 and 1.0 micro-g/kg/min, and intravenously in the same rabbits in doses of 0.01, 0.1, 1.0 and 10 micro-g/kg/min. Each dose was infused for 15 min. No intrarenal dose of milrinone altered plasma renin activity or arterial pressure, although at the highest dose, there was a small increase in heart rate. Intravenous infusion of milrinone at 1.0 micro-g/kg/min increased plasma renin activity to 176 +/- 55% of the control value (P less than 0.05). Heart rate increased but arterial pressure did not change. Intravenous infusion of milrinone at 1O micro-g/kg/min increased plasma renin activity to 386 +/- 193% of control in association with a decrease in arterial pressure and an increase in heart rate. These results confirm that milrinone increases renin secretion, and indicate that the stimulation is due to an extrarenal effect of the drug.

  18. Intravenous amino acids in third trimester isolated oligohydramnios

    International Nuclear Information System (INIS)

    Qureshi, F.U.

    2011-01-01

    To determine the efficacy of maternal administration of intravenous amino acid solution in improving amniotic fluid volume in cases of isolated oligohydramnios and to observe its impact on mode of delivery and neonatal outcome. Study Design: A prospective case series. Methodology: Forty two women with singleton pregnancy, well established gestational age and clinically and sonographically proven isolated oligohydramnios in the third trimester before 36 weeks were administered amino acid solution intravenously after excluding cases of premature rupture of membranes, congenital anomaly of fetus, maternal pulmonary, cardiovascular and hypertensive disorders, and severe placental insufficiency (raised S/D ratio). Pre-infusion and postinfusion Amniotic fluid Index (AFI) was measured and repeated weekly. Women were followed till delivery. Results: According to repeated measurement analysis of variance, mean pre-infusion AFI was 4.7 cm, mean one week postinfusion AFI was 5.8 cm, mean two week post-infusion AFI was 6.2 cm and mean three week AFI was 6.3 cm (p-value 0.029, significant). Cesarean section became a predominant mode of delivery in this group without a firm evidence of associated fetal compromise. Conclusion: Amino acid infusion is an effective therapy for raising AFI in isolated oligohydramnios in this case series. Liberal use of cesarean section in this selected group should be carefully re-evaluated. (author)

  19. Intravenous coronary angiography using the orbital radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ohtsuka, Sadanori; Yamaguchi, Iwao; Wu, Jin; Takeda, Toru; Itai, Yuji; Maruhashi, Akira [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Hyodo, Kazuyuki; Ando, Masami [High Energy Accelerator Research Org., Tsukuba, Ibaraki (Japan). Inst. of Materials Structure Science

    2002-09-01

    This review described the progress and current status of intravenous coronary angiography (IVCAG) using the orbital radiation generated by the synchrotron. Authors diagnosed 4 patients of coronary artery disease in 1996 and 33 until 2000. Monochromatic 2-D X-ray beam (2.0 X 10{sup 10} photons/mm{sup 2}/sec, 130 X 75 mm) of 37 keV was obtained by non-symmetrical reflection of synchrotron radiation generated by 5.0 GeV accelerated electron. The use of 2-D beam enabled to give the dynamic IVCAG image in contrast with the static image by the 1-D slit beam. Intermittent irradiation (5 msec/100 msec) reduced the exposure dose to <750 mSv. Images were recorded in the Sony digital video-recorder placed behind the Sony Charge-coupled device (CCD) camera and Toshiba photo-multiplier, and gave the precision of 1 mm of the artery. The IVCAG by synchrotron radiation reduced patients' burden and was expected to be more widely used in future. (K.H.)

  20. Floating arterial thrombus related stroke treated by intravenous thrombolysis.

    Science.gov (United States)

    Vanacker, P; Cordier, M; Janbieh, J; Federau, C; Michel, P

    2014-01-01

    The effects of intravenous thrombolysis on floating thrombi in cervical and intracranial arteries of acute ischemic stroke patients are unknown. Similarly, the best prevention methods of early recurrences remain controversial. This study aimed to describe the clinical and radiological outcome of thrombolyzed strokes with floating thrombi. We retrospectively analyzed all thrombolyzed stroke patients in our institution between 2003 and 2010 with floating thrombi on acute CT-angiography before the intravenous thrombolysis. The floating thrombus was diagnosed if an elongated thrombus of at least 5 mm length, completely surrounded by contrast on supra-aortic neck or intracerebral arteries, was present on CT-angiography. Demographics, vascular risk factors, and comorbidities were recorded and stroke etiology was determined after a standardized workup. Repeat arterial imaging was performed by CTA at 24 h or before if clinical worsening was noted and then by Doppler and MRA during the first week and at four months. Of 409 thrombolyzed stroke patients undergoing acute CT Angiography, seven (1.7%) had a floating thrombus; of these seven, six had it in the anterior circulation. Demographics, risk factors and stroke severity of these patients were comparable to the other thrombolyzed patients. After intravenous thrombolysis, the floating thrombi resolved completely at 24 h in four of the patients, whereas one had an early recurrent stroke and one developed progressive worsening. One patient developed early occlusion of the carotid artery with floating thrombus and subsequently a TIA. The two patients with a stable floating thrombus had no clinical recurrences. In the literature, only one of four reported cases were found to have a thrombolysis-related early recurrence. Long-term outcome seemed similar in thrombolyzed patients with floating thrombus, despite a possible increase of very early recurrence. It remains to be established whether acute mechanical thrombectomy could be

  1. Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L

    2016-08-01

    Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights

  2. Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation.

    Directory of Open Access Journals (Sweden)

    Niklas Lofruthe

    Full Text Available Intravenous iron supplementation is an effective therapy in iron deficiency anemia (IDA, but controversial in anemia of inflammation (AI. Unbound iron can be used by bacteria and viruses for their replication and enhance the inflammatory response. Nowadays available high molecular weight iron complexes for intravenous iron substitution, such as ferric carboxymaltose, might be useful in AI, as these pharmaceuticals deliver low doses of free iron over a prolonged period of time. We tested the effects of intravenous iron carboxymaltose in murine AI: Wild-type mice were exposed to the heat-killed Brucella abortus (BA model and treated with or without high molecular weight intravenous iron. 4h after BA injection followed by 2h after intravenous iron treatment, inflammatory cytokines were upregulated by BA, but not enhanced by iron treatment. In long term experiments, mice were fed a regular or an iron deficient diet and then treated with intravenous iron or saline 14 days after BA injection. Iron treatment in mice with BA-induced AI was effective 24h after iron administration. In contrast, mice with IDA (on iron deficiency diet prior to BA-IA required 7d to recover from AI. In these experiments, inflammatory markers were not further induced in iron-treated compared to vehicle-treated BA-injected mice. These results demonstrate that intravenous iron supplementation effectively treated the murine BA-induced AI without further enhancement of the inflammatory response. Studies in humans have to reveal treatment options for AI in patients.

  3. Safety of Intravenous Application of Mistletoe (Viscum album L. Preparations in Oncology: An Observational Study

    Directory of Open Access Journals (Sweden)

    Megan L. Steele

    2014-01-01

    Full Text Available Background. Traditional mistletoe therapy in cancer patients involves subcutaneous applications of Viscum album L. preparations, with doses slowly increasing based on patient responses. Intravenous infusion of high doses may improve therapeutic outcomes and is becoming more common. Little is known about the safety of this “off-label” application of mistletoe. Methods. An observational study was performed within the Network Oncology. Treatment with intravenous mistletoe applications is described. The frequency of adverse drug reactions (ADRs to intravenous mistletoe applications was calculated and compared to ADR data from a study on subcutaneous applications. Results. Of 475 cancer patients who received intravenous infusions of Helixor, Abnoba viscum, or Iscador mistletoe preparations, 22 patients (4.6% reported 32 ADRs of mild (59.4% or moderate severity (40.6%. No serious ADRs occurred. ADRs were more frequently reported to i.v. mistletoe administered alone (4.3%, versus prior to chemotherapy (1.6%. ADR frequency differed with respect to preparation type, with Iscador preparations showing a higher relative frequency, compared to Abnoba viscum and Helixor. Overall, patients were almost two times less likely to experience an ADR to intravenous compared to subcutaneous application of mistletoe. Conclusion. Intravenous mistletoe therapy was found to be safe and prospective studies for efficacy are recommended.

  4. Efeitos da associação entre pequenas doses subaracnóideas de morfina e cetoprofeno venoso e oral em pacientes submetidas à cesariana Efectos de la asociación entre pequeñas dosis subaracnóideas de morfina y cetoprofeno venoso y oral en pacientes sometidas a cesariana Effects of low spinal morphine doses associated to intravenous and oral ketoprofen in patients submitted to cesarean sections

    Directory of Open Access Journals (Sweden)

    Eliana Marisa Ganem

    2003-08-01

    de efectos colaterales en pacientes sometidas a cesariana, bajo anestesia subaracnóidea con bupivacaína hiperbárica y morfina en las dosis de 0,05 mg y 0,1 mg, asociadas al cetoprofeno por las vías venosa y oral. MÉTODO: Participaron del estudio 60 gestantes de término, estado físico ASA I y II, que fueron sometidas a cesariana electiva. Las pacientes fueron divididas en dos grupos: grupo 1 - morfina 0,1 mg, grupo 2 - 0,05 mg, asociada a 15 mg de bupivacaína hiperbárica. Todas recibieron cetoprofeno (100 mg por vía venosa en el per-operatorio y por vía oral a cada 8 horas en el primer día del pos-operatorio. Las pacientes fueron evaluadas 6, 12 y 24 horas después del término de la cirugía, con relación a la intensidad del dolor y presencia de efectos colaterales (sedación, prurito, náusea y vómito. La presencia de estos últimos también fue evaluada en el per-operatorio. RESULTADOS: Ambos grupos fueron idénticos cuanto a los datos antropométricos y la duración de la cirugía y de la anestesia. También fueron homogéneos con relación a la intensidad del dolor pos-operatorio y a la presencia de prurito, sedación, náusea y vómito. CONCLUSIONES: La morfina, en las dosis de 0,05 mg y 0,1 mg administradas en el espacio subaracnóideo, asociada al cetoprofeno por las vías venosa y oral, presentó la misma calidad de analgesia pos-operatoria y determinó la misma ocurrencia de efectos colaterales.BACKGROUND AND OBJECTIVES: Low spinal morphine doses are effective in relieving postoperative pain of patients submitted to Cesarean sections, with low incidence of side-effects. This study aimed at evaluating postoperative analgesia and the incidence of side-effects in patients submitted to Cesarean sections under spinal anesthesia with hyperbaric bupivacaine and 0.05 mg and 0.1 mg morphine associated to intravenous and oral ketoprofen. METHODS: Sixty pregnant women, physical status ASA I and II, undergoing elective Cesarean sections, were divided in

  5. REVIEW ARTICLE – Intravenous paracetamol in pediatrics: A global perspective

    Directory of Open Access Journals (Sweden)

    Muzammil Irshad, MBBS

    2012-12-01

    Full Text Available Intravenous (IV Paracetamol is an excellent post operative analgesic and antipyretic in children. Efficacy and tolerability of IV Propacetamol have been established in pediatric practice. It is believed that paracetamol works by inhibiting cyclooxygenase-2 (COX-2 enzymes. Studies bring to light that therapeutic doses of IV acetaminophen are effective and tolerable in children with least chances of hepatotoxicity. However, overdose toxicity has been reported in children and drug induced hypotension in febrile critically ill patients. Therapeutic doses according to body weight of neonates and children can be administered in hospital settings. Special education of health care staff regarding precise dose and solution is necessary to assess the role of IV paracetamol preparation in pediatric practice.

  6. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  7. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  8. Intentional intravenous mercury injection | Yudelowitz | South African ...

    African Journals Online (AJOL)

    Intravenous mercury injection is rarely seen, with few documented cases. Treatment strategies are not clearly defined for such cases, although a few options do show benefit. This case report describes a 29-year-old man suffering from bipolar disorder, who presented following self-inflicted intravenous injection of mercury.

  9. Quantum repeated games revisited

    International Nuclear Information System (INIS)

    Frąckiewicz, Piotr

    2012-01-01

    We present a scheme for playing quantum repeated 2 × 2 games based on Marinatto and Weber’s approach to quantum games. As a potential application, we study the twice repeated Prisoner’s Dilemma game. We show that results not available in the classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games proposed by Iqbal and Toor. We point out the drawbacks that make their results unacceptable. (paper)

  10. Clinical experience with intravenous radiosensitizers in unresectable sarcomas

    International Nuclear Information System (INIS)

    Kinsella, T.J.; Glatstein, E.

    1987-01-01

    Traditionally, adult bone and soft tissue sarcomas have been considered to be ''radioresistant.'' Because of this philosophy, patients who present with locally advanced, unresectable sarcomas often are treated in a palliative fashion, usually with low-dose radiotherapy. Over the last 6 years, 29 patients with unresectable primary or metastatic sarcomas were treated using a combination of intravenous chemical radiosensitizers and high-dose irradiation. Twenty-two of 29 patients achieved clinical local control, with six patients having a complete clinical response. The time to tumor response is often several months or longer, which is in contrast to other tumor histologies (carcinomas, lymphomas), where tumor response usually occurs over several weeks. Several large tumors have shown only a minimal tumor response, yet were found to be sterilized in posttreatment biopsy or autopsy examination. Of 15 patients with primary sarcomas without metastases, 11 patients (73%) remain free of local tumor progression from 12 to 83 months. Adult high-grade sarcomas can be controlled with high-dose radiotherapy and intravenous radiosensitizers, although the precise role of these agents is unclear

  11. Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

    Science.gov (United States)

    El-Kersh, Karim; Ruf, Kathryn M; Smith, J Shaun

    There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

  12. Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous administration of dipyridamole

    International Nuclear Information System (INIS)

    Taillefer, R.; Lette, J.; Phaneuf, D.C.; Leveille, J.; Lemire, F.; Essiambre, R.

    1986-01-01

    Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 images. It is concluded from this study that thallium-201 myocardial imaging after coronary vasodilation with a 400 mg oral dose of dipyridamole is a safe, widely available and reliable alternative for the evaluation of coronary artery disease in patients unable to achieve an adequate exercise level on stress testing

  13. Evaluation of the repeated-dose liver and gastrointestinal tract micronucleus assays with 22 chemicals using young adult rats: summary of the collaborative study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/The Japanese Environmental Mutagen Society (JEMS) - Mammalian Mutagenicity Study Group (MMS).

    Science.gov (United States)

    Hamada, Shuichi; Ohyama, Wakako; Takashima, Rie; Shimada, Keisuke; Matsumoto, Kazumi; Kawakami, Satoru; Uno, Fuyumi; Sui, Hajime; Shimada, Yasushi; Imamura, Tadashi; Matsumura, Shoji; Sanada, Hisakazu; Inoue, Kenji; Muto, Shigeharu; Ogawa, Izumi; Hayashi, Aya; Takayanagi, Tomomi; Ogiwara, Yosuke; Maeda, Akihisa; Okada, Emiko; Terashima, Yukari; Takasawa, Hironao; Narumi, Kazunori; Wako, Yumi; Kawasako, Kazufumi; Sano, Masaki; Ohashi, Nobuyuki; Morita, Takeshi; Kojima, Hajime; Honma, Masamitsu; Hayashi, Makoto

    2015-03-01

    The repeated-dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect hepatocarcinogens. We conducted a collaborative study to assess the performance of this assay and to evaluate the possibility of integrating it into general toxicological studies. Twenty-four testing laboratories belonging to the Mammalian Mutagenicity Study Group, a subgroup of the Japanese Environmental Mutagen Society, participated in this trial. Twenty-two model chemicals, including some hepatocarcinogens, were tested in 14- and/or 28-day RDLMN assays. As a result, 14 out of the 16 hepatocarcinogens were positive, including 9 genotoxic hepatocarcinogens, which were reported negative in the bone marrow/peripheral blood micronucleus (MN) assay by a single treatment. These outcomes show the high sensitivity of the RDLMN assay to hepatocarcinogens. Regarding the specificity, 4 out of the 6 non-liver targeted genotoxic carcinogens gave negative responses. This shows the high organ specificity of the RDLMN assay. In addition to the RDLMN assay, we simultaneously conducted gastrointestinal tract MN assays using 6 of the above carcinogens as an optional trial of the collaborative study. The MN assay using the glandular stomach, which is the first contact site of the test chemical when administered by oral gavage, was able to detect chromosomal aberrations with 3 test chemicals including a stomach-targeted carcinogen. The treatment regime was the 14- and/or 28-day repeated-dose, and the regime is sufficiently promising to incorporate these methods into repeated-dose toxicological studies. The outcomes of our collaborative study indicated that the new techniques to detect chromosomal aberrations in vivo in several tissues worked successfully. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Repeat migration and disappointment.

    Science.gov (United States)

    Grant, E K; Vanderkamp, J

    1986-01-01

    This article investigates the determinants of repeat migration among the 44 regions of Canada, using information from a large micro-database which spans the period 1968 to 1971. The explanation of repeat migration probabilities is a difficult task, and this attempt is only partly successful. May of the explanatory variables are not significant, and the overall explanatory power of the equations is not high. In the area of personal characteristics, the variables related to age, sex, and marital status are generally significant and with expected signs. The distance variable has a strongly positive effect on onward move probabilities. Variables related to prior migration experience have an important impact that differs between return and onward probabilities. In particular, the occurrence of prior moves has a striking effect on the probability of onward migration. The variable representing disappointment, or relative success of the initial move, plays a significant role in explaining repeat migration probabilities. The disappointment variable represents the ratio of actural versus expected wage income in the year after the initial move, and its effect on both repeat migration probabilities is always negative and almost always highly significant. The repeat probabilities diminish after a year's stay in the destination region, but disappointment in the most recent year still has a bearing on the delayed repeat probabilities. While the quantitative impact of the disappointment variable is not large, it is difficult to draw comparisons since similar estimates are not available elsewhere.

  15. Comparative study of intravenous urographic bolus (I.U.B.) and intravenous urographic infusion (I.U.I.) in dogs

    International Nuclear Information System (INIS)

    Thibaut L, Julio; Ditzel, G.; Vargas, L; Born, R; Deppe G, Rodolfo

    1996-01-01

    Two urographic methods were compared: the intravenous urographic bolus (i.u.b.) and the intravenous urographic infusion (i.u.i.). In both methods, two groups of seven healthy adult dogs of both sexes, weighing7.0 to 16.5 kg were used and were anaesthesized with 2% thiopentone sodium in doses of 20 mg/kg via cephalica. In the i.u.b., meglumine diatrizoate (Hypaque-M, 60%) was injected via saphena with a concentration of 282 mg of iodine per mi in doses of 564 mg of iodine per kg. In the i.u.i., meglumine diatrizoate was injected via saphena by drip infusion with a concentration of 200 mg of iodine per mi in doses of 500 mg of iodine per kg. Three series of two X-rays each were taken in ventrodorsal projection 1, 4 and 8 min and left lateral recumbency 30 sec after administering the contrast medium. The X-ray plates obtained were analyzed and compared intra and inter group considering the advance speed of the contrast medium, the radiographic density and outline, and kidney size. The advance speed of the contrast medium was higher in the i.u.i., reaching the kidney, ureter and bladder 1 min after administration in both projections; in ventrodorsal projections in the i.u.b. only the kidneys were reached while in the left lateral recumbency, the kidney and ureters were reached [es

  16. Effects of single and repeated doses of the calcium antagonist felodipine on blood pressure, renal function, electrolytes and water balance, and renin-angiotensin-aldosterone system in hypertensive patients.

    Science.gov (United States)

    Leonetti, G; Gradnik, R; Terzoli, L; Fruscio, M; Rupoli, L; Cuspidi, C; Sampieri, L; Zanchetti, A

    1986-01-01

    Doses of 10 mg b.i.d. of the new dihydropyridine calcium antagonist, felodipine, were tested for seven consecutive days in 11 hospitalized hypertensive patients. A significant reduction of both systolic and diastolic blood pressures, with patients in both the supine and upright positions, occurred immediately after the first dose and was maintained (daily average 15%) throughout the following days. An increase in heart rate was observed after the first dose (15 and 23 beats/min, in supine and upright postures), and subsequently declined to average values of 8 and 14 beats/min on the seventh day. There was a marked natriuretic response during the first and second day, during which an average negative sodium balance of 95 mmol developed; on the following days sodium output was not significantly different from control, but a negative balance averaging 135 mmol was still present on the seventh day of felodipine administration. A moderate negative potassium balance also progressively developed and reached -48 mmol on the seventh day. Glomerular filtration rate was unchanged, but renal plasma flow increased significantly during administration of felodipine. Plasma renin activity and plasma aldosterone were also increased very moderately by felodipine. Compared with previous observations by our group with higher doses of felodipine (12.5, 25, and 50 mg t.i.d.), 10 mg b.i.d. of this new calcium antagonist appear to exert a marked and prolonged blood pressure reduction, accompanied by a definite natriuretic instead of an antinatriuretic effect.

  17. Safety profile of the intravenous administration of brain-targeted stable nucleic acid lipid particles

    Directory of Open Access Journals (Sweden)

    Mariana Conceição

    2016-03-01

    Full Text Available In a clinical setting, where multiple administrations of the therapeutic agent are usually required to improve the therapeutic outcome, it is crucial to assess the immunogenicity of the administered nanoparticles. In this data work, we investigated the safety profile of the repeated intravenous administration of brain-targeted stable nucleic acid lipid particles (RVG-9r-targeted SNALPs. To evaluate local activation of the immune system, we performed analysis of mouse tissue homogenates and sections from cerebellum. To investigate peripheral activation of the immune system, we used serum of mice that were intravenously injected with RVG-9r-targeted SNALPs. These data are related and were discussed in the accompanying research article entitled “Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado–Joseph disease neurological phenotype” (Conceição et al., in press [1].

  18. Perineural versus intravenous clonidine as an adjuvant to Bupivacaine in supraclavicular Brachial plexus block

    Directory of Open Access Journals (Sweden)

    Vikram Bedi

    2017-07-01

    Conclusion: Addition of clonidine 2mcg/kg to 28 ml of 0.5% bupivacaine in brachial plexus blocks results in a faster onset, increased duration of block and longer postoperative pain relief when compared to bupivacaine alone. These advantages are not observed when the same dose of clonidine is injected intravenously.

  19. Reversal of progressive necrotizing vasculitis with intravenous pulse cyclophosphamide and methylprednisolone.

    Science.gov (United States)

    Fort, J G; Abruzzo, J L

    1988-09-01

    We describe a patient with polyarteritis nodosa who, despite therapy with daily doses of oral prednisone and cyclophosphamide, developed acute renal failure. Renal histopathologic examination demonstrated crescentic glomerulonephritis. Treatment with intravenous pulse cyclophosphamide and methylprednisolone resulted in clinical improvement and significant recovery of renal function.

  20. Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery

    NARCIS (Netherlands)

    Prins, Sandra A.; van Dijk, Monique; van Leeuwen, Pim; Searle, Susan; Anderson, Brian J.; Tibboel, Dick; Mathot, Ron A. A.

    2008-01-01

    The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. During surgery all infants (6 months-2 years) received a rectal loading dose of 40 mg.kg(-1) paracetamol 2 h

  1. Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery

    NARCIS (Netherlands)

    Prins, Sandra A.; Van Dijk, Monique; Van Leeuwen, Pim; Searle, Susan; Anderson, Brian J.; Tibboel, Dick; Mathot, Ron A. A.

    Background: The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. Methods: During surgery all infants (6 months-2 years) received a rectal loading dose of 40

  2. Acute effect of oral, intraperitoneal, and intravenous 1 alpha-hydroxycholecalciferol on markers of bone metabolism

    DEFF Research Database (Denmark)

    Joffe, P; Ladefoged, S D; Cintin, C

    1994-01-01

    ,25-(OH)2D3 was measured. DESIGN: Single doses of 1 alpha-OHD3 (80 ng/kg body wt) were given in randomized cross-over fashion, orally, intraperitoneally (i.p.) and intravenously (i.v.) on three occasions. Blood was sampled at 0, 1, 6, 12, and 24 h after administration of 1 alpha-OHD3. MAIN RESULTS...

  3. Intravenous and inhalation toxicokinetics of sarin stereoisomers in atropinized guinea pigs

    NARCIS (Netherlands)

    Spruit, W.E.T.; Langenberg, J.P.; Trap, H.C.; Wiel, H.J. van der; Helmich, R.B.; Helden, H.P.M. van; Benschop, H.P.

    2000-01-01

    We report the first toxicokinetic studies of (±)-sarin. The toxicokinetics of the stereoisomers of this nerve agent were studied in anesthetized, atropinized, and restrained guinea pigs after intravenous bolus administration of a dose corresponding to 0.8 LD50 and after nose-only exposure to vapor

  4. The Pentapeptide Repeat Proteins

    OpenAIRE

    Vetting, Matthew W.; Hegde, Subray S.; Fajardo, J. Eduardo; Fiser, Andras; Roderick, Steven L.; Takiff, Howard E.; Blanchard, John S.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S,T,A,V][D,N][L,F]-[S,T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Myc...

  5. Rectal dihydroartemisinin versus intravenous quinine in the ...

    African Journals Online (AJOL)

    Rectal dihydroartemisinin versus intravenous quinine in the treatment of severe malaria: A randomised clinical trial. F Esamai, P Ayuo, W Owino-Ongor, J Rotich, A Ngindu, A Obala, F Ogaro, L Quoqiao, G Xingbo, L Guangqian ...

  6. INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

    Directory of Open Access Journals (Sweden)

    E. Y. Ponomareva

    2014-07-01

    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  7. INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

    Directory of Open Access Journals (Sweden)

    E. Y. Ponomareva

    2011-01-01

    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  8. Clinical perspectives of intravenous ketamine anaesthesia in peafowl (Pavo cristatus).

    Science.gov (United States)

    Athar, M; Shakoor, A; Muhammad, G; Sarwar, M N; Chaudhry, N I

    1996-01-01

    A total of 29 peafowl (Pavo cristatus), rectified surgically for infraorbital abscesses (n = 22), lacerated wounds (n = 4), and fractures of tibia (n = 2) and radius (n = 1), were anaesthetized by the intravenous administration of ketamine hydrochloride (Inj. Calypsol, Gedeon Richter, Hungary) in a dose of 15 20 mg/kg body weight. Divided doses (10 mg + 5 mg + 5 mg) were used with an interval of 1-2 min. No premedication was undertaken in any of the birds. Anaesthesia lasted for about 15 min and the birds gained their feet completely after 30 min to 3 hours. The respiration rate was markedly depressed (8-10/min) and the respiratory pattern was deep abdominal. Only a slight increase was observed in the heart rate. Analgesia was incomplete and muscle relaxation was not satisfactory. Mild salivation was also noticed in some of the birds (n = 3). Recovery, although not smooth, was uneventful.

  9. Phase I and pharmacokinetic study of the combination of topotecan and ifosfamide administered intravenously every 3 weeks

    NARCIS (Netherlands)

    Kerbusch, T.; Groenewegen, G.; Mathôt, R. A. A.; Herben, V. M. M.; ten Bokkel Huinink, W. W.; Swart, M.; Ambaum, B.; Rosing, H.; Jansen, S.; Voest, E. E.; Beijnen, J. H.; Schellens, J. H. M.

    2004-01-01

    To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and pharmacokinetics of topotecan administered as a 30-min intravenous (i.v.) infusion over 5 days in combination with a 1-h i.v. infusion of ifosfamide (IF) for 3 consecutive days every 3 weeks. Patients with advanced

  10. Hypersensitivity reaction with intravenous GnRH after pulsatile subcutaneous GnRH treatment in male hypogonadotrophic hypogonadism.

    OpenAIRE

    Popović, V.; Milosević, Z.; Djukanović, R.; Micić, D.; Nesović, M.; Manojlović, D.; Djordjević, P.; Mićić, J.

    1988-01-01

    Chronic pulsatile subcutaneous administration of low doses of gonadotrophin releasing hormone (GnRH) is an effective therapy for men with hypogonadotrophic hypogonadism. Hypersensitivity reactions to GnRH are rare. We wish to report hypersensitivity reactions with intravenous GnRH after low dose subcutaneous pulsatile GnRH treatment in two men with hypogonadotrophic hypogonadism due to suprasellar disease.

  11. Intravenous iron-containing products: EMA procrastination.

    Science.gov (United States)

    2014-07-01

    A European reassessment has led to identical changes in the summaries of product characteristics (SPCs) for all intravenous iron-containing products: the risk of serious adverse effects is now highlighted, underlining the fact that intravenous iron-containing products should only be used when the benefits clearly outweigh the harms. Unfortunately, iron dextran still remains on the market despite a higher risk of hypersensitivity reactions than with iron sucrose.

  12. Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride.

    Science.gov (United States)

    Wu, George; Powers, Dan; Yeung, Stanley; Chen, Frank; Neelon, Kelly

    2018-01-01

    Prophylaxis or therapy with a combination of a neurokinin 1 (NK-1) receptor antagonist (RA), a 5-hydroxytryptamine- 3 (5-HT3) RA, and dexamethasone is recommended by international antiemesis guidelines for the prevention of chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy and for select patients receiving moderately emetogenic chemotherapy. VARUBI (rolapitant) is a substance P/NK-1 RA that was recently approved by the U.S. Food and Drug Administration as an injectable emulsion in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Granisetron Hydrochloride Injection USP is one of the 5-HT3 RAs indicated for the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin. Herein, we describe the physical and chemical compatibility and stability of VARUBI (rolapitant) injectable emulsion (166.5 mg/92.5 mL [1.8 mg/mL], equivalent to 185 mg of rolapitant hydrochloride) admixed with Granisetron Hydrochloride Injection USP (1.0 mg/mL, equivalent to 1.12 mg/mL hydrochloride). Binary admixtures of VARUBI injectable emulsion and Granisetron Hydrochloride Injection USP were prepared and stored in VARUBI ready-to-use glass vials and in four types of commonly used intravenous administration (tubing) sets. Evaluation of the physical and chemical compatibility and stability of the admixtures in the VARUBI ready-to-use vials stored at room temperature (20°C to 25°C) under fluorescent light and under refrigeration (2°C to 8°C protected from light) was conducted at 0, 1, 6, 24, and 48 hours, and that of the admixtures in the intravenous tubing sets was evaluated at 0, 2, and 6 hours of storage at 20°C to 25°C. Physical stability was evaluated by visual examination

  13. Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

    Science.gov (United States)

    Liu, Dongzhou J; Collaku, Agron

    2018-01-01

    Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

  14. Repeated Causal Decision Making

    Science.gov (United States)

    Hagmayer, York; Meder, Bjorn

    2013-01-01

    Many of our decisions refer to actions that have a causal impact on the external environment. Such actions may not only allow for the mere learning of expected values or utilities but also for acquiring knowledge about the causal structure of our world. We used a repeated decision-making paradigm to examine what kind of knowledge people acquire in…

  15. simple sequence repeat (SSR)

    African Journals Online (AJOL)

    In the present study, 78 mapped simple sequence repeat (SSR) markers representing 11 linkage groups of adzuki bean were evaluated for transferability to mungbean and related Vigna spp. 41 markers amplified characteristic bands in at least one Vigna species. The transferability percentage across the genotypes ranged ...

  16. Effect of Intravenous Infusion Solutions on Bioelectrical Impedance Spectroscopy.

    Science.gov (United States)

    Yap, Jason; Rafii, Mahroukh; Azcue, Maria; Pencharz, Paul

    2017-05-01

    Bioelectrical impedance (BIA) is often used to measure body fluid spaces and thereby body composition. However, in acute animal studies, we found that impedance was driven by the saline content of intravenous (IV) fluids and not by the volume. The aim of the study was to investigate the effect of 3 different fluids acutely administered on the change in impedance, specifically resistance (R). Nine healthy adults participated in 3 treatment (0.9% saline, 5% dextrose, and a mixture of 0.3% saline + 3.3% dextrose) experiments on nonconsecutive days. They all received 1 L of one of the treatments intravenously over a 1-hour period. Repeated BIA measurements were performed prior to IV infusion and then every 5 minutes for the 1-hour infusion period, plus 3 more measurements up to 15 minutes after the completion of the infusion. The change in R in the 0.9% saline infusion experiment was significantly lower than that of the glucose and mixture treatment ( P < .001). Bioelectrical impedance spectroscopy and BIA measure salt rather than the volume changes over the infusion period. Hence, in patients receiving IV fluids, BIA of any kind (single frequency or multifrequency) cannot be used to measure body fluid spaces or body composition.

  17. Digital repeat analysis; setup and operation.

    Science.gov (United States)

    Nol, J; Isouard, G; Mirecki, J

    2006-06-01

    Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

  18. Modelling Framework and Assistive Device for Peripheral Intravenous Injections

    Science.gov (United States)

    Kam, Kin F.; Robinson, Martin P.; Gilbert, Mathew A.; Pelah, Adar

    2016-02-01

    Intravenous access for blood sampling or drug administration that requires peripheral venepuncture is perhaps the most common invasive procedure practiced in hospitals, clinics and general practice surgeries.We describe an idealised mathematical framework for modelling the dynamics of the peripheral venepuncture process. Basic assumptions of the model are confirmed through motion analysis of needle trajectories during venepuncture, taken from video recordings of a skilled practitioner injecting into a practice kit. The framework is also applied to the design and construction of a proposed device for accurate needle guidance during venepuncture administration, assessed as consistent and repeatable in application and does not lead to over puncture. The study provides insights into the ubiquitous peripheral venepuncture process and may contribute to applications in training and in the design of new devices, including for use in robotic automation.

  19. Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants.

    Science.gov (United States)

    Krekels, Elke H J; van Ham, Saskia; Allegaert, Karel; de Hoon, Jan; Tibboel, Dick; Danhof, Meindert; Knibbe, Catherijne A J

    2015-09-01

    Based on recovered metabolite ratios in urine, it has been concluded that paracetamol glucuronidation may be up-regulated upon multiple dosing. This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling approach. A population pharmacokinetic model was developed in NONMEM VI, based on paracetamol plasma concentrations from 54 preterm and term neonates and infants, and on paracetamol, paracetamol-glucuronide and paracetamol-sulphate amounts in urine from 22 of these patients. Patients received either a single intravenous propacetamol dose or up to 12 repeated doses. Paracetamol and metabolite disposition was best described with one-compartment models. The formation clearance of paracetamol-sulphate was 1.46 mL/min/kg(1.4), which was about 5.5 times higher than the formation clearance of the glucuronide of 0.266 mL/min/kg. The renal excretion rate constants of both metabolites was estimated to be 11.4 times higher than the excretion rate constant of unchanged paracetamol, yielding values of 0.580 mL/min/kg. Developmental changes were best described by bodyweight in linear relationships on the distribution volumes, the formation of paracetamol-glucuronide and the unchanged excretion of paracetamol, and in an exponential relationship on the formation of paracetamol-sulphate. There was no evidence for up-regulation or other time-varying changes in any of the model parameters. Simulations with this model illustrate how paracetamol-glucuronide recovery in urine increases over time due to the slower formation of this metabolite and in the absence of up-regulation. Developmental changes, described by bodyweight-based functions, rather than up-regulation, explain developmental changes in paracetamol disposition in neonates and infants.

  20. Safety of Repeated Yttrium-90 Radioembolization

    International Nuclear Information System (INIS)

    Lam, Marnix G. E. H.; Louie, John D.; Iagaru, Andrei H.; Goris, Michael L.; Sze, Daniel Y.

    2013-01-01

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver’s cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51–71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction

  1. Safety of Repeated Yttrium-90 Radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Marnix G. E. H.; Louie, John D. [Stanford University School of Medicine, Division of Interventional Radiology (United States); Iagaru, Andrei H.; Goris, Michael L. [Stanford University School of Medicine, Division of Nuclear Medicine (United States); Sze, Daniel Y., E-mail: dansze@stanford.edu [Stanford University School of Medicine, Division of Interventional Radiology (United States)

    2013-10-15

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  2. A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

    Science.gov (United States)

    Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

    2014-03-01

    The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  3. Epidural versus intravenous steroids application following percutaneous endoscopic lumbar discectomy.

    Science.gov (United States)

    Hu, Annan; Gu, Xin; Guan, Xiaofei; Fan, Guoxin; He, Shisheng

    2018-05-01

    Retrospectively study.The purpose of this study was to compare the effects of intraoperative epidural steroids and single dose intravenous steroids following a percutaneous endoscopic lumbar discectomy (PELD).Inflammatory irritation of dorsal root ganglia or sensory nerve roots may cause postoperative pain. Epidural steroids have been applied after a lumbar discectomy for more than 20 years. Epidural steroid application after a PELD is easier to perform and safer because the operations are under observation of the scope.We retrospectively reviewed the medical records of patients with lumbar intervertebral disc herniation who had undergone transforaminal PELD at our department. There are 60 patients in epidural steroid group, intravenous steroid group, and control group, respectively. Visual analog scores (VAS) and the Oswestry Disability Index (ODI) were collected. Successful pain control is defined as 50% or more reduction in back and leg pain (VAS scores).VAS scores (back and leg) and ODI showed a significant decrease in all groups when comparing pre- and postoperatively. Epidural steroid group had a significant improvement in successful pain control compared with the control group at 2 weeks of follow-up. VAS scores (leg) in the epidural steroid group showed a significant decrease compared with the intravenous steroids group at 1, 3, and 7 days after the surgery, but this difference had no statistical significance at 1, 6, and 12 months of follow-up. All groups did not show a significant difference in ODI at 1, 6, and 12 months follow-up.Epidural application of steroid has a better effect on controlling the postoperative pain of PELD in the short term. The epidural application of steroid did not show a tendency to cause infection.

  4. Disposition of nasal, intravenous, and oral methadone in healthy volunteers.

    Science.gov (United States)

    Dale, Ola; Hoffer, Christine; Sheffels, Pamela; Kharasch, Evan D

    2002-11-01

    Nasal administration of many opioids demonstrates rapid uptake and fast onset of action. Nasal administration may be an alternative to intravenous and oral administration of methadone and was therefore studied in human volunteers. The study was approved by the Institutional Review Board of the University of Washington, Seattle. Eight healthy volunteers (6 men and 2 women) aged 19 to 33 years were enrolled after informed written consent was obtained. Subjects received 10 mg methadone hydrochloride nasally, orally, or intravenously on 3 separate occasions in a crossover design. Nasal methadone (50 mg/mL in aqueous solution) was given as a 100-microL spray in each nostril (Pfeiffer BiDose sprayer). Blood samples for liquid chromatography-mass spectrometry analyses of methadone and the metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were drawn for up to 96 hours. The methadone effect was measured by noninvasive infrared pupilometry coincident with blood sampling. Nasal uptake of methadone was rapid, with maximum plasma concentrations occurring within 7 minutes. The maximum effects of intravenous, nasal, and oral methadone, on the basis of dark-adapted pupil diameter, were reached in about 15 minutes, 30 minutes, and 2 hours, respectively. The respective durations were 24, 10, and 8 hours. Both nasal and oral bioavailabilities were 0.85. Subjects reported that nasal methadone caused a burning sensation. Nasal administration of methadone results in rapid absorption and onset of effect and high bioavailability, which was greater than that reported for other nasal opioids, with a similar duration of effect. Nasal administration may be an alternative route of methadone administration; however, improved formulations are desirable to reduce nasal irritation.

  5. Remifentanil Prevents Withdrawal Movements Caused by Intravenous Injection of Rocuronium

    Science.gov (United States)

    Choi, Byung In; Choi, Seung Ho; Shin, Yang-Sik; Lee, Sung Jin; Yoon, Kyung Bong; Shin, Seo Kyung

    2008-01-01

    Purpose The incidence of pain induced withdrawal movement following intravenous injection of rocuronium is high. This randomized, double-blind, placebo-controlled study was designed to evaluate the effect of pretreatment of remifentanil on the withdrawal movements due to intravenous injection of rocuronium during anesthetic induction. Materials and Methods Ninety adult female patients undergoing thyroidectomy were randomly allocated to three groups. Each patient intravenously received one of three solutions of equal volume (4 mL): normal saline (Group I, n = 30), 0.5 µg/kg remifentanil (Group II, n = 30) or 1 µg/kg remifentanil (Group III, n = 30). Thirty seconds after remifentanil administration, anesthesia was induced with 5 mg/kg IV thiopental. Twenty seconds after thiopental injection, 0.6 mg/kg IV rocuronium was administered (injection rate of 0.5 mL/sec) and patients' withdrawal movements were assessed. Mean arterial pressure (MAP) and heart rate were assessed on arrival in the operation room, before the tracheal intubation and immediately, 1 and 2 min after the tracheal intubation. Results The incidence of withdrawal movements was significantly lower in both of the remifentanil groups (3 and 0% in Group II and III, respectively) than in the saline group (70%). Remifentanil attenuated the increase of heart rate and MAP immediately and 1 min after the tracheal intubation. Conclusion The pretreatment with 0.5 and 1.0 µg/kg remifentanil of bolus doses prevented the withdrawal movements caused by rocuronium injection, and effectively blunted cardiovascular activation following tracheal intubation. PMID:18452256

  6. Intravenous human immunoglobulins for refractory recurrent pericarditis: a systematic review of all published cases.

    Science.gov (United States)

    Imazio, Massimo; Lazaros, George; Picardi, Elisa; Vasileiou, Panagiotis; Carraro, Mara; Tousoulis, Dimitrios; Belli, Riccardo; Gaita, Fiorenzo

    2016-04-01

    Refractory recurrent pericarditis is a major clinical challenge after colchicine failure, especially in corticosteroid-dependent patients. Human intravenous immunoglobulins (IVIGs) have been proposed as possible therapeutic options for these cases. The goal of this systematic review is to assess the efficacy and safety of IVIGs in this context. Studies reporting the use of IVIG for the treatment of recurrent pericarditis and published up to October 2014 were searched in several databases. All references found, upon initial assessment at title and abstract level for suitability, were consequently retrieved as full reports for further appraisal. Among the 18 citations retrieved, 17 reports (4 case series and 13 single case reports, with an overall population of 30 patients) were included. The mean disease duration was 14 months and the mean number of recurrences before IVIG was 3. Approximately 47% of patients had idiopathic recurrent pericarditis, 10% had an infective cause, and the remainder a systemic inflammatory disease. Nineteen out of the 30 patients (63.3%) were on corticosteroids at IVIG commencement. IVIGs were generally administered at a dose of 400-500 mg/kg/day for 5 consecutive days with repeated cycles according to the clinical response. Complications were uncommon (headache in ~3%) and not life-threatening. After a mean follow-up of approximately 33th months, recurrences occurred in 26.6% of cases after the first IVIG cycle, and 22 of the 30 patients (73.3%) were recurrence-free. Five patients (16.6%) were on corticosteroids at the end of the follow-up. IVIGs are rapidly acting, well tolerated, and efficacious steroid-sparing agents in refractory pericarditis.

  7. Treatment of a mild chronic case of ciguatera fish poisoning with intravenous mannitol, a case study.

    Science.gov (United States)

    Mitchell, Gary

    2005-03-01

    This article describes a recent case of ciguatera poisoning treated with intravenous mannitol. Mannitol has been used with good effect in non-controlled studies in acutely severely poisoned patients, but is not described in the treatment of chronic or milder poisoning. Our patient was a 35-year-old Niuean man who had eaten a ciguatoxic fish two weeks previously. His symptoms were not severe but were very unpleasant and restricted his ability to work. He was given a single dose of mannitol (0.66g/kg) as an intravenous infusion over two hours. His symptoms dramatically improved within 24 hours, and within a few days he felt virtually back to his former self. He experienced no side effects to the mannitol. It is suggested that intravenous mannitol may prove to be a useful treatment for mild to moderate ciguatera poisoning, and for patients who present late for treatment.

  8. Combined use of intravenous anesthetics and hypothermia in treating refractory status epilepticus

    Directory of Open Access Journals (Sweden)

    Guo-ping REN

    2015-11-01

    Full Text Available The primary choice of treating refractory status epilepticus (RSE is intravenous anesthetics, but the seizures of some patients can not get a good control. Thus, other therapies must be combined. Hypothermia not only can terminate seizures, but also play a part in brain protection. Though combined use of intravenous anesthetics and hypothermia is not a regular clinical scheme, the favorable effect has been proved by a lot of clinical research. This paper mainly focuses on the dose of intravenous anesthetics, the time, temperature and procedure of hypothermia, the indications and contraindications of combined therapy, and so on. DOI: 10.3969/j.issn.1672-6731.2015.11.006

  9. Comparison of the image quality of intravenous urograms using low-osmolar contrast media

    International Nuclear Information System (INIS)

    Kaye, B.; Howard, J.; Foord, K.D.; Cumberland, D.C.

    1988-01-01

    Almost equivalent, intravenous iodine doses of the three new low-osmolar contrast media, ioxaglate (Hexabrix), iopamidol (Niopam) and iohexol (Omnipaque) have been compared for image quality on the intravenous urogram. Generally good radiographic images were obtained. Iohexol gave better results for the nephrogram and pelvicalyceal distension compared with the other contrast media, but only the nephrogram results were statistically significant. Pyelographic density and ureteric distension and density were similar with all three contrast media. In patients where low-osmolality contrast media need to be used for intravenous urography, we suggest that iohexol gives the best radiographic images. Other factors, such as cost and the relative incidence of side-effects of the low-osmolar contrast media also need to be taken into consideration. (author)

  10. [Peripheral intravenous catheter-related phlebitis].

    Science.gov (United States)

    van der Sar-van der Brugge, Simone; Posthuma, E F M Ward

    2011-01-01

    Phlebitis is a very common complication of the use of intravenous catheters. Two patients with an i.v. catheter complicated by thrombophlebitis are described. Patient A was immunocompromised due to chronic lymphatic leukaemia and developed septic thrombophlebitis with positive blood cultures for S. Aureus. Patient B was being treated with flucloxacillin because of an S. Aureus infection and developed chemical phlebitis. Septic phlebitis is rare, but potentially serious. Chemical or mechanical types of thrombophlebitis are usually less severe, but happen very frequently. Risk factors include: female sex, previous episode of phlebitis, insertion at (ventral) forearm, emergency placement and administration of antibiotics. Until recently, routine replacement of peripheral intravenous catheters after 72-96 h was recommended, but randomised controlled trials have not shown any benefit of this routine. A recent Cochrane Review recommends replacement of peripheral intravenous catheters when clinically indicated only.

  11. Emergency department treatment of viral gastritis using intravenous ondansetron or dexamethasone in children.

    Science.gov (United States)

    Stork, Christine M; Brown, Kathleen M; Reilly, Tracey H; Secreti, LaLaina; Brown, Lawrence H

    2006-10-01

    To compare the efficacy of intravenous ondansetron or dexamethasone compared with intravenous fluid therapy alone in children presenting to the emergency department with refractory vomiting from viral gastritis who had failed attempts at oral hydration. This double-blind, randomized, controlled trial was performed in a tertiary care pediatric emergency department. Children aged 6 months to 12 years presenting with more than three episodes of vomiting in the past 24 hours, mild/moderate dehydration, and failed oral hydration were included. Patients with other medical causes were excluded. Subjects were randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at 10-20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those not tolerating oral fluids at four hours were admitted. Discharged patients were evaluated at 24 and 72 hours for vomiting and repeat health care visits. The primary study outcome was hospitalization rates between the groups. Data were analyzed using chi-square test, Kruskal-Wallis test, Mantel-Haenszel test, and analysis of variance, with p hydration than NS-treated patients (29 [67.4%]; relative risk, 1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in number of mean episodes of vomiting or repeat visits to health care at 24 and 72 hours in the ondansetron, dexamethasone, or NS groups. In children with dehydration secondary to vomiting from acute viral gastritis, ondansetron with intravenous rehydration improves tolerance of oral fluids after two hours and reduces the hospital admission rate when compared with intravenous rehydration with or without dexamethasone.

  12. Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Palonosetron Hydrochloride Injection and Dexamethasone Sodium Phosphate Injection.

    Science.gov (United States)

    Wu, George; Powers, Dan; Yeung, Stanley; Chen, Frank

    2018-01-01

    Prophylaxis or therapy with a combination of a neurokinin 1 (NK-1) receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone is recommended by international antiemesis guidelines for the prevention of chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy and for selected patients receiving moderately emetogenic chemotherapy. VARUBI (rolapitant) is a substance P/NK-1 RA that was recently approved by the U.S. Food and Drug Administration as an injectable emulsion in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Palonosetron is one of the 5-HT3 RAs indicated for the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin. Herein, we describe the physical and chemical compatibility and stability of VARUBI injectable emulsion (166.5 mg/92.5 mL [1.8 mg/mL, free base], equivalent to 185 mg of rolapitant hydrochloride) admixed with palonosetron injection 0.25 mg free base in 5 mL (equivalent to 0.28 mg hydrochloride salt) and with either 5 mL (20 mg) or 2.5 mL (10 mg) of dexamethasone sodium phosphate. Admixtures were prepared and stored in VARUBI injectable emulsion ready-to-use glass vials as supplied by the rolapitant manufacturer and in four types of commonly used intravenous administration (tubing) sets. Assessment of the physical and chemical compatibility and stability of the admixtures in the VARUBI ready-to-use vials stored at room temperature (20°C to 25°C) under fluorescent light and under refrigeration (2°C to 8°C protected from light) was conducted at 0, 1, 6, 24, and 48 hours, and that of the admixtures in the intravenous tubing sets was evaluated at 0, 2, and 6 hours of storage at 20°C to 25°C. Physical stability

  13. Use of intravenous immunoglobulins in clinical practice

    Directory of Open Access Journals (Sweden)

    E.K. Donyush

    2011-01-01

    Full Text Available Immunoglobulins are main component of immune defense; they take part in anti-infectious resistance of organism and regulate processes of different immune reactions. Intravenous immunoglobulins are the most frequently used products made from donor blood plasma. The need in these drugs is steadily increasing during last 15–20 years, and indications are widening due to modern hightechnology methods of production and cleaning. The article presents modern data on formula, mechanisms of action and indications for different groups of intravenous immunoglobulins (standard, hyperimmune, fortified and description of possible adverse events.Key words: immuglobulines, prophylaxis, treatment, unfavorable reaction, children.

  14. Intravenous nitroglycerin as an experimental model of vascular headache. Basic characteristics

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg; Olesen, J; Tfelt-Hansen, P

    1989-01-01

    To develop a reliable experimental model of vascular headache, we studied the dose-response relationship between headache and i.v. nitroglycerin (NTG) in 10 healthy subjects. NTG was infused intravenously over periods of 10 min separated by wash-out periods. Doses of 0.25, 0.50, 1.00 and 2......) at various doses and declined rapidly after NTG discontinuation. Wash-out periods of 10-20 min were sufficient. The reproducibility of headache intensity and character was satisfactory in the retest experiment. There were no unpleasant side effects and no visible flushing. Thus blindness was maintained. I...

  15. Intravenous digital subtraction angiography contrast media time-concentration curves

    International Nuclear Information System (INIS)

    Burbank, F.H.; Brody, W.R.

    1985-01-01

    At any specified radiation dose and system signal-to-noise ratio, temporal (masked-mode) intravenous digital subtraction angiography (IV-DSA) image quality is dependent upon the shape of the arterial time-concentration curve produced by the intravenous injection of iodinated contrast media. If contrast media appears in the arterial circulation as a compact bolus and reaches a high peak, images containing low or no iodine (the mask image or images) and high iodine concentration (the enhanced image or images) can be obtained close together in time, maximizing contrast media enhancement and minimizing the potential for spatial movement (misregistration). However, if the contrast media bolus is broad, rising slowly to a low concentration peak, sufficient time may pass for movement to occur and the opacification difference between the mask image and the enhanced image may be too small to visualize vessels of interest. Consequently, knowledge of the rules which govern the formation of time-concentration curves is central to IV-DSA

  16. Intravenous vs. left ventricular injection of ionic contrast material: hemodynamic implications for digital subtraction angiography

    International Nuclear Information System (INIS)

    Mancini, G.B.; Ostrander, D.R.; Slutsky, R.A.; Shabetai, R.; Higgins, C.B.

    1983-01-01

    Because of the increased use of intravenous injection of contrast material for the evaluation of cardiac structure and function by digital subtraction techniques, a study was done to assess the hemodynamic effects of contrast material when used in this fashion in man. In 10 patients, with each serving as his own control, the effects of intravenous and intraventricular injections of sodium meglumine diatrizoate (Renografin 76) in the same dose were compared. There was no difference between these two methods with respect to changes in pulmonary wedge pressures, systemic pressures, and pulmonary vascular resistance. The elevation of mean pulmonary artery and right atrial pressure was greater after the intraventricular injection (p <0.05). The elevated cardiac output and systemic vascular resistance returned to control values somewhat more quickly after the intravenous injection (p<0.001 and p<0.05, respectively); and the increase in cardiac output was greater after the intravenous injection at 1 min (p<0.05), but less than after the intraventricular injection at 2 min (p<0.05). Despite the detection of these statistically significant differences, the magnitude and timing of these differences are too small to justify the notion that imaging by intravenous injections of standard ionic contrast media provides any substantial hemodynamic benefits or decreased risk to the patient

  17. Action of 50 R X-ray doses on the breeding function of C3H strain mice - effect of splitting the dose, action of repeated irradiations on successive generations; Action de 50 R de rayons X sur la fonction de reproduction des souris de race C3H - influence du fractionnement. Action de la repetition des irradiations au cours des generations successives

    Energy Technology Data Exchange (ETDEWEB)

    Alix, D [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires

    1965-07-01

    X-rays exposure effect was studied on C3H strain mice, at the standpoint of the effects produced on breeding function. The method used with this purpose was the following: single doses 20 - 30 - 40 and 50 R/dose, fractional doses: 50 R/total dose, divided in 2 - 5 - 10 or 25 irradiations distributed in one month duration. The offsprings were irradiated at the same doses than the parents, consanguinity being maintained. Statistical treatment of results was carried out, that led at the following conclusions: 1) Couples receiving single exposure of 50 R or two exposures of 25 R at one month interval give comparable results. Fractional doses do not involve the slightest diminution of X-rays effect. 2) 30 R exposure brings about a decrease in fertility, with an increase in abortions. Fertility of 20 R irradiated couples remains below controls. 3) After ten times 5 R and twenty-five 2 R, the number of abortions is the largest. Ovarian function is particularly sensitive to X-rays; one may think that twenty-five 2 R give injuries conditioning non-viability of conception products, smaller doses should produce mutations and yield births of altered genotype individuals. (author) [French] L'action d'une exposition aux rayons X de souris de race C3H a ete etudiee du point de vue des effets produits sur la fonction reproductrice. La methode utilisee fut la suivante: doses administrees en irradiation unique: 20 - 30 - 40 et 50 R/seance, en irradiations fractionnees: 50 R au total en 2 - 5 - 10 ou 25 seances reparties en un mois. Les descendants ont ete irradies aux memes doses que leurs parents, en maintenant la consanguinite. Un traitement statistique des resultats a ete effectue dont on a pu conclure : 1) Chez les couples ayant recu une seule exposition de 50 R ou deux expositions de 25 R a intervalle d'un mois les resultats sont comparables. Le fractionnement n' entrainant aucune attenuation de l'action des rayons X. 2) Une exposition de 30 R entraine une baisse de fecondite

  18. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-12-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation (MLI) has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five Glenn Research Center (GRC) provided coupons with 25 layers was shown to be +/- 8.4% whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0%. A second group of 10 coupons has been fabricated by Yetispace and tested by Florida State University, the repeatability between coupons has been shown to be +/- 15-25%. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  19. Renal effects of the non-ionic contrast medium iopentol after intravenous injection in healthy volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Jakobsen, J.A.; Berg, K.J.; Waaler, A.; Andrew, E. (Rikshospitalet, Oslo (Norway). Dept. of Radiology Rikshospitalet, Oslo (Norway). Renal Section Nycomed A/S, Oslo (Norway). Dept. of Clinical Research and Development)

    1990-01-01

    Renal effects of the new non-ionic contrast medium iopentol in increasing doses were assessed and compared with the effects of physiologic saline. Twenty-four healthy male volunteers, allocated to three dose groups, were given iopentol intravenously in doses of 0.3, 0.6, and 1.2 g I/kg body weight, respectively. The highest dose group was also given physiologic saline separately as a control. The diuresis increased in all groups, most in the highest dose group, and with a concomitant fall of urine osmolality and increase in osmolar clearance. A slight decrease of serum osmolality, creatinine and urea occurred at 3 hours due to hemodilution. The glomerular filtration rate was unaffected by iopentol. The urinary excretion of albumin and {beta}{sub 2}-microglobulin was unchanged. However, urinary N-acetyl-{beta}-glucosaminidase and alkaline phosphatase increased significantly, most in the highest dose group. All changes were reversible. (orig.).

  20. Effect of intravenous amino acids on interdigestive antroduodenal motility and small bowel transit time.

    Science.gov (United States)

    Gielkens, H A; van den Biggelaar, A; Vecht, J; Onkenhout, W; Lamers, C B; Masclee, A A

    1999-02-01

    Patients on total parenteral nutrition have an increased risk of developing gallstones because of gall bladder hypomotility. High dose amino acids may prevent biliary stasis by stimulating gall bladder emptying. To investigate whether intravenous amino acids also influence antroduodenal motility. Eight healthy volunteers received, on three separate occasions, intravenous saline (control), low dose amino acids (LDA), or high dose amino acids (HDA). Antroduodenal motility was recorded by perfusion manometry and duodenocaecal transit time (DCTT) using the lactulose breath hydrogen test. DCTT was significantly prolonged during LDA and HDA treatment compared with control. The interdigestive motor pattern was maintained and migrating motor complex (MMC) cycle length was significantly reduced during HDA compared with control and LDA due to a significant reduction in phase II duration. Significantly fewer phase IIIs originated in the gastric antrum during LDA and HDA compared with control. Duodenal phase II motility index was significantly reduced during HDA, but not during LDA, compared with control. Separate intravenous infusion of high doses of amino acids in healthy volunteers: (1) modulates interdigestive antroduodenal motility; (2) shortens MMC cycle length due to a reduced duration of phase II with a lower contractile incidence both in the antrum and duodenum (phase I remains unchanged whereas the effect on phase III is diverse: in the antrum phase III is suppressed and in the duodenum the frequency is increased); and (3) prolongs interdigestive DCTT.

  1. Assessment of the pharmacodynamics of intranasal, intravenous and oral scopolamine

    Science.gov (United States)

    Tietze, Karen J.

    1990-01-01

    Space motion sickness is an important issue in the space medical sciences program. One of the objectives of the ongoing clinical experimental protocol Pharmacokinetics of Intranasal Scopolamine in Normal Subjects is to evaluate the pharmacodynamics of scopolamine using salivary flow rate and pH profiles and cognitive performance tests as pharmacodynamic parameters. Normal volunteers collected saliva and performed the NTI Multiresource Performance Battery tests at designed time intervals to establish control saliva flow rates, salivary pH profiles, and the characteristics of the learning curve for the performance program under normal conditions. In the clinical part of the study, saliva samples and performance test scores are collected from healthy nonsmoking subjects after receiving a single 0.4 mg dose of either intranasal, intravenous, or oral scopolamine.

  2. Intravenous Immunoglobulin in the Treatment of Primary Immunodeficiency Diseases.

    Science.gov (United States)

    De Ranieri, Deirdre; Fenny, Nana Sarkoah

    2017-01-01

    Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases (PIDDs) for more than 50 years. Its role as a therapeutic agent has expanded over the past couple of decades as its anti-inflammatory and immune-modulatory mechanisms of action have been elucidated. It is now used "off-label" to treat other autoimmune diseases. This article focuses on the role of IVIG in the treatment of PIDDs characterized by absent or deficient antibody production. Replacement doses are given on a monthly basis in these conditions as a prophylactic measure to prevent acute and serious bacterial infections. [Pediatr Ann. 2017;46(1):e8-e12.]. Copyright 2017, SLACK Incorporated.

  3. Urinary iron excretion induced by intravenous infusion of deferoxamine in ß-thalassemia homozygous patients

    Directory of Open Access Journals (Sweden)

    Boturão-Neto E.

    2002-01-01

    Full Text Available The purpose of the present study was to identify noninvasive methods to evaluate the severity of iron overload in transfusion-dependent ß-thalassemia and the efficiency of intensive intravenous therapy as an additional tool for the treatment of iron-overloaded patients. Iron overload was evaluated for 26 ß-thalassemia homozygous patients, and 14 of them were submitted to intensive chelation therapy with high doses of intravenous deferoxamine (DF. Patients were classified into six groups of increasing clinical severity and were divided into compliant and non-compliant patients depending on their adherence to chronic chelation treatment. Several methods were used as indicators of iron overload. Total gain of transfusion iron, plasma ferritin, and urinary iron excretion in response to 20 to 60 mg/day subcutaneous DF for 8 to 12 h daily are useful to identify iron overload; however, urinary iron excretion in response to 9 g intravenous DF over 24 h and the increase of urinary iron excretion induced by high doses of the chelator are more reliable to identify different degrees of iron overload because of their correlation with the clinical grades of secondary hemochromatosis and the significant differences observed between the groups of compliant and non-compliant patients. Finally, the use of 3-9 g intravenous DF for 6-12 days led to a urinary iron excretion corresponding to 4.1 to 22.4% of the annual transfusion iron gain. Therefore, continuous intravenous DF at high doses may be an additional treatment for these patients, as a complement to the regular subcutaneous infusion at home, but requires individual planning and close monitoring of adverse reactions.

  4. Clinical Evaluation of Ciprofloxacin Intravenous Preparation ...

    African Journals Online (AJOL)

    The most common site of bacteria infection in humans is the urinary tract. For nosocomial infections it is the catheterized urinary tract. Compromised immune responses in hospitalized patients contribute to the difficulties encountered in treating their infections. In these patients, administration of intravenous antibiotic is ...

  5. The adverse effects of inadvertent intraoperative intravenous ...

    African Journals Online (AJOL)

    Inadvertent intravenous injection of 1% phenylephrine (10 mg) induced severe hypertension and tachycardia in a previously healthy female patient undergoing elective gynaecological surgery. This medical error was investigated using the criticalincident technique that is available in our department. This case report ...

  6. [Phlebitis associated to intravenous/infusional therapy].

    Science.gov (United States)

    Nicotera, Raffaela

    2011-01-01

    Phlebitis is a common problem associated to intravenous therapies, it may cause pain, sepsis and increased duration of hospitalization. Several factors can increase the risk of phlebitis. The literature review addresses the mechanisms of chemical phlebitis, the characteristics of drugs likely to cause a phlebitis and the main measures to be adopted for prevention and treatment.

  7. Campaign best practice in intravenous therapy.

    Science.gov (United States)

    Baldwin, Wayne; Murphy, Jayne; Shakespeare, David; Kelly, Chris; Fox, Louise; Kelly, Matthew

    Intravenous therapy is an integral part of nursing care but is associated with a high risk of infection. This article outlines a campaign that aimed to increase awareness of best practice for IV therapy and reduce the risks of healthcare-associated IV infections in hospital and community settings.

  8. Intravenous voriconazole after toxic oral administration

    NARCIS (Netherlands)

    Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

    In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

  9. Complex intravenous anesthesia in interventional procedures

    International Nuclear Information System (INIS)

    Xie Zonggui; Hu Yuanming; Huang Yunlong; You Yong; Wu Juan; Huang Zengping; Li Jian

    2006-01-01

    Objective: To evaluate the value and safety of Diprivan and Fentany intravenous administration of analgesia in interventional procedures. Methods: Diprivan with Fentany intravenous administration for analgesia was used in eighty interventional procedures of sixty-five patients, without tracheal tube insertion. Vital signs including HR, BP, arterial oxygen saturation (SpO 2 ) and patients' reaction to operating were recorded. Results: Intravenous anesthesia was cared out successfully in eighty interventional procedures, with patients under sleeping condition during the operation, together with no pain and no agony memory of the procedure. The amount of Diprivan was 500±100 mg and Fentany was 0.2±0.025 mg. Mean arterial pressure and SpO 2 were 11.4±2.2 kPa, 10.6±2.1 kPa and 98±1.0, 96±1.5 respectively before and after ten minutes of the operation, with no significant difference. Conclusions: Diprivan with Fentany intravenous administration for interventional procedure analgesia possess good safety, painless and no agony memory of the procedure; therefor ought to be recommended. (authors)

  10. The impact of using an intravenous workflow management system (IVWMS) on cost and patient safety.

    Science.gov (United States)

    Lin, Alex C; Deng, Yihong; Thaibah, Hilal; Hingl, John; Penm, Jonathan; Ivey, Marianne F; Thomas, Mark

    2018-07-01

    The aim of this study was to determine the financial costs associated with wasted and missing doses before and after the implementation of an intravenous workflow management system (IVWMS) and to quantify the number and the rate of detected intravenous (IV) preparation errors. A retrospective analysis of the sample hospital information system database was conducted using three months of data before and after the implementation of an IVWMS System (DoseEdge ® ) which uses barcode scanning and photographic technologies to track and verify each step of the preparation process. The financial impact associated with wasted and missing >IV doses was determined by combining drug acquisition, labor, accessory, and disposal costs. The intercepted error reports and pharmacist detected error reports were drawn from the IVWMS to quantify the number of errors by defined error categories. The total number of IV doses prepared before and after the implementation of the IVWMS system were 110,963 and 101,765 doses, respectively. The adoption of the IVWMS significantly reduced the amount of wasted and missing IV doses by 14,176 and 2268 doses, respectively (p system was $144,019 over 3 months. The total number of errors detected was 1160 (1.14%) after using the IVWMS. The implementation of the IVWMS facilitated workflow changes that led to a positive impact on cost and patient safety. The implementation of the IVWMS increased patient safety by enforcing standard operating procedures and bar code verifications. Published by Elsevier B.V.

  11. Repeat Customer Success in Extension

    Science.gov (United States)

    Bess, Melissa M.; Traub, Sarah M.

    2013-01-01

    Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

  12. 78 FR 65594 - Vehicular Repeaters

    Science.gov (United States)

    2013-11-01

    ... coordinators estimate the effect on coordination fees? Does the supposed benefit that mobile repeater stations... allow the licensing and operation of vehicular repeater systems and other mobile repeaters by public... email: [email protected] or phone: 202-418- 0530 or TTY: 202-418-0432. For detailed instructions for...

  13. Comparative study of clindamycin concentration in the cerebrospinal fluid after intravenous and intrathecal administration in patients with toxoplasmic meningoencephalitis

    Directory of Open Access Journals (Sweden)

    Сергій Петрович Борщов

    2015-07-01

    Full Text Available Aim of the work: to study the difference of clindamycin concentration in CSF at the intravenous and combined (intrathecal + intravenous ways of administration of preparation.Materials and methods: study was carried out at the treatment of 11 HIV-positive patients 27-63 years old (men and women with toxoplasmic meningoencephalitises.There was measured the clindamycin concentration in CSF of every patient after intravenous and combined (intrathecal + intravenous ways of administration of preparation. The determinations of concentration were done by the way of the reverse-phase high-performance liquid chromatography (HPLC with ultraviolet (UV detection. Statistic processing of the received data was carried out using the Wilcoxon criterion.Results of research. There was received the statistically significant increase of clindamycin concentration in CSF of patients in a day after combined (intrathecal + intravenous administration of preparation comparing with an intravenous administration.Conclusions. 1. Intrathecal administration of 150 mg. of clindamycin with 8 mg. of dexamethasone is safe.2. Intrathecal administration of 150 mg. of clindamycin with 8 mg. of dexamethasone in combination with an intravenous administration of preparation leads to statistically significant increase of clindamycin concentration in CSF at least during a day after injection.3. Intrathecal administration of clindamycin with dexamethasone in offered doses can be recommended for treatment of meningoencephalitises that caused by microorganisms susceptible to clindamycin.4. If the therapy of toxoplasmic meningoencephalitis was started with an intravenous prescription of clindamycin it is recommended an additional treatment with an intrathecal administration of clindamycin with dexamethasone in offered doses to increase efficiency by creating an effective concentration of preparation in the nidus of infection.5. Intrathecal methods of therapy must be used by the specialists of

  14. Short-term intravenous antimicrobial prophylaxis for elective rectal cancer surgery: results of a prospective randomized non-inferiority trial.

    Science.gov (United States)

    Ishibashi, Keiichiro; Ishida, Hideyuki; Kuwabara, Kouki; Ohsawa, Tomonori; Okada, Norimichi; Yokoyama, Masaru; Kumamoto, Kensuke

    2014-04-01

    To investigate the non-inferiority of postoperative single-dose intravenous antimicrobial prophylaxis to multiple-dose intravenous antimicrobial prophylaxis in terms of the incidence of surgical site infections (SSIs) in patients undergoing elective rectal cancer surgery by a prospective randomized study. Patients undergoing elective surgery for rectal cancer were randomized to receive a single intravenous injection of flomoxef (group 1) or five additional doses (group 2) of flomoxef after the surgery. All the patients had received preoperative oral antibiotic prophylaxis (kanamycin and erythromycin) after mechanical cleansing within 24 h prior to surgery, and had received intravenous flomoxef during surgery. A total of 279 patients (including 139 patients in group 1 and 140 in group 2) were enrolled in the study. The incidence of SSIs was 13.7% in group 1 and 13.6% in group 2 (difference [95% confidence interval]: -0.2% [-0.9 to 0.7%]). The incidence of SSIs was not significantly different in patients undergoing elective rectal surgery who were treated using a single dose of postoperative antibiotics compared to those treated using multiple-dose antibiotics when preoperative mechanical and chemical bowel preparations were employed.

  15. The effect of tubing dwell time on insulin adsorption during intravenous insulin infusions.

    Science.gov (United States)

    Thompson, Cecilia D; Vital-Carona, Jessica; Faustino, E Vincent S

    2012-10-01

    Insulin adsorbs to plastic tubing, which decreases the concentration of an insulin solution delivered from an intravenous infusion set. Dwelling insulin within tubing before starting the infusion decreases adsorption but delays treatment initiation and wastes time in infusion preparation. The lack of data on dwell time effects results in wide variability in practice. We aim to determine the effect of dwell time on insulin concentration from intravenous infusion tubing. In this in vitro study, we used insulin solutions with concentrations of 0.1 unit/mL, 1 unit/mL, and 10 units/mL. Each solution dwelled in intravenous infusion sets for 0, 15, 30, or 60 min. After the dwell, we measured insulin concentrations from the solution bags and tubing. We repeated each insulin concentration-dwell time combination five times. Comparisons were performed using analyses of variance. For each of the three insulin concentrations, the mean insulin concentrations from the tubing were not significantly different between dwell times. Duration of dwell time did not affect insulin adsorption in polypropylene intravenous infusion sets. We recommend that following a 20-mL flush, insulin infusions can be started without any dwell time. Removal of dwell times may improve clinical practice by minimizing preparation time and will allow faster initiation of insulin infusion therapy.

  16. Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy.

    Science.gov (United States)

    Letko, Erik; Yeh, Steven; Foster, C Stephen; Pleyer, Uwe; Brigell, Mitchell; Grosskreutz, Cynthia L

    2015-05-01

    Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to patients with active, chronic, noninfectious uveitis. This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in patients with noninfectious uveitis. Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial. Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy. Patients were randomized to secukinumab 300 mg SC every 2 weeks for 4 doses, secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or secukinumab 30 mg/kg IV every 4 weeks for 2 doses. Intravenous or SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose). Percentage of patients with treatment response, defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening. Percentage of patients with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening. Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC dose, produced higher responder rates (72.7% and 61.5% vs. 33.3%, respectively) and remission rates (27.3% and 38.5% vs. 16.7%, respectively). Statistical and clinical superiority for the 30 mg/kg IV dose compared with the 300 mg SC dose was established in a Bayesian probability model. Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring IV dosing. Secukinumab, administered in IV or SC formulations, appeared

  17. Intravenous/oral ciprofloxacin therapy versus intravenous ceftazidime therapy for selected bacterial infections.

    Science.gov (United States)

    Gaut, P L; Carron, W C; Ching, W T; Meyer, R D

    1989-11-30

    The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms.

  18. Optimal timing for intravenous administration set replacement.

    Science.gov (United States)

    Gillies, D; O'Riordan, L; Wallen, M; Morrison, A; Rankin, K; Nagy, S

    2005-10-19

    Administration of intravenous therapy is a common occurrence within the hospital setting. Routine replacement of administration sets has been advocated to reduce intravenous infusion contamination. If decreasing the frequency of changing intravenous administration sets does not increase infection rates, a change in practice could result in considerable cost savings. The objective of this review was to identify the optimal interval for the routine replacement of intravenous administration sets when infusate or parenteral nutrition (lipid and non-lipid) solutions are administered to people in hospital via central or peripheral venous catheters. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, EMBASE: all from inception to February 2004; reference lists of identified trials, and bibliographies of published reviews. We also contacted researchers in the field. We did not have a language restriction. We included all randomized or quasi-randomized controlled trials addressing the frequency of replacing intravenous administration sets when parenteral nutrition (lipid and non-lipid containing solutions) or infusions (excluding blood) were administered to people in hospital via a central or peripheral catheter. Two authors assessed all potentially relevant studies. We resolved disagreements between the two authors by discussion with a third author. We collected data for the outcomes; infusate contamination; infusate-related bloodstream infection; catheter contamination; catheter-related bloodstream infection; all-cause bloodstream infection and all-cause mortality. We identified 23 references for review. We excluded eight of these studies; five because they did not fit the inclusion criteria and three because of inadequate data. We extracted data from the remaining 15 references (13 studies) with 4783 participants. We conclude that there is no evidence that changing intravenous administration sets more often than every 96 hours

  19. Intravenous Topiramate: Pharmacokinetics in Dogs with Naturally-Occurring Epilepsy

    Directory of Open Access Journals (Sweden)

    Irene Vuu

    2016-12-01

    Full Text Available Barriers to developing treatments for human status epilepticus (SE include the inadequacy of experimental animal models. In contrast, naturally-occurring canine epilepsy is similar to the human condition and can serve as a platform to translate research from rodents to humans. The objectives of this study were to characterize the pharmacokinetics (PK of an intravenous (IV dose of topiramate (TPM in dogs with epilepsy, and evaluate its effect on intracranial electroencephalographic (iEEG features. Five dogs with naturally occurring epilepsy were used for this study. Three were getting at least one antiseizure drug as maintenance therapy including phenobarbital (PB. Four (ID 1-4 were used for the 10 mg/kg IV TPM + PO TPM study, and three (ID 3-5 were used for the 20 mg/kg IV TPM study. IV TPM was infused over 5 minutes at both doses. The animals were observed for vomiting, diarrhea, ataxia, and lethargy. Blood samples were collected at scheduled pre- and post-dose times. Plasma concentrations were measured using a validated HPLC-MS method. Non-compartmental and population compartmental modeling were performed (Phoenix WinNonLin and NLME using plasma concentrations from all dogs in the study. Intracranial EEG (iEEG was acquired in one dog. The difference between averaged iEEG energy levels at 15 minutes pre- and post-dose was assessed using a Kruskal-Wallis test. No adverse events were noted. Topiramate concentration-time profiles were best fit by a two-compartment model. PB co-administration was associated with a 5.6 fold greater clearance and a ~4 fold shorter elimination half-life. iEEG data showed that TPM produced a significant energy increase at frequencies >4 Hz across all 16 electrodes within 15 minutes of dosing. Simulations suggested that dogs on an enzyme inducer would require 25 mg/kg, while dogs on non-inducing drugs would need 20 mg/kg to attain the target concentration (20-30 µg/mL at 30-minutes post-dose.This study shows that IV

  20. Intravenous Lacosamide in Pediatric Status Epilepticus: An Open-Label Efficacy and Safety Study.

    Science.gov (United States)

    Poddar, Karan; Sharma, Rohan; Ng, Yu-Tze

    2016-08-01

    Lacosamide is an antiepilepsy drug approved by the Food and Drug Administration for patients aged 17 years and older for partial-onset seizures as monotherapy or adjunctive therapy. We reviewed the use of intravenous lacosamide in children aged less than 17 years with status epilepticus. Children who received at least one dose of intravenous lacosamide for status epilepticus at our tertiary care children's hospital from December 2011 to March 2014 were studied. Status epilepticus was defined as continuous seizure activity for longer than 20 minutes or two or more recurrent seizures without regaining baseline level of awareness. Efficacy was defined as seizure freedom or more than 50% reduction of seizures within 24 hours of administering lacosamide. Nine children with a mean age of 5.7 years (range: three months to 16 years) were included. The mean initial or loading dose was 8.7 mg/kg, with seven of nine patients receiving a dose of 10 mg/kg. The average total amount of intravenous lacosamide administered within the initial 24 hours was 13.8 mg/kg. Lacosamide was found to be efficacious in seven of nine (77.8%) patients. Four patients (44.4%) became seizure free. Two patients continued to have status epilepticus within 24 hours of lacosamide administration. Bradycardia was observed in one patient. In children with status epilepticus, intravenous lacosamide was efficacious in 78% of the patients and 44% become seizure free. In addition, no significant adverse reactions were observed. An appropriate safe, effective initial, or loading dose may be 10 mg/kg. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Repeated causal decision making.

    Science.gov (United States)

    Hagmayer, York; Meder, Björn

    2013-01-01

    Many of our decisions refer to actions that have a causal impact on the external environment. Such actions may not only allow for the mere learning of expected values or utilities but also for acquiring knowledge about the causal structure of our world. We used a repeated decision-making paradigm to examine what kind of knowledge people acquire in such situations and how they use their knowledge to adapt to changes in the decision context. Our studies show that decision makers' behavior is strongly contingent on their causal beliefs and that people exploit their causal knowledge to assess the consequences of changes in the decision problem. A high consistency between hypotheses about causal structure, causally expected values, and actual choices was observed. The experiments show that (a) existing causal hypotheses guide the interpretation of decision feedback, (b) consequences of decisions are used to revise existing causal beliefs, and (c) decision makers use the experienced feedback to induce a causal model of the choice situation even when they have no initial causal hypotheses, which (d) enables them to adapt their choices to changes of the decision problem. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  2. Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants

    Directory of Open Access Journals (Sweden)

    Mukae Takehiro

    2011-09-01

    Full Text Available Abstract Background Fibromyalgia (FM is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS. Results In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief. Conclusions These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.

  3. Characterization of an intravenously injected bolus

    International Nuclear Information System (INIS)

    Samuel, A.M.; Raikar, U.R.; Atmaram, S.H.; Ganatra, R.D.

    1976-01-01

    A study of some parameters affecting the time activity histogram of an intravenous bolus injection of radioactivity was performed. A scoring system for bolus compactness was attempted. A score of 2 and above was considered to be a satisfactory bolus. Volumes less than 1 ml tended to result in a satisfactory bolus. The nature of radiopharmaceutical injected, different injecters and age of the patient did not affect the score. Thyrotoxic patients gave the best bolus score. (orig.) [de

  4. Intrathecal morphine is superior to intravenous PCA in patients undergoing minimally invasive cardiac surgery

    Directory of Open Access Journals (Sweden)

    Chirojit Mukherjee

    2012-01-01

    Full Text Available Aim of our study was to evaluate the beneficial effect of low dose intrathecal morphine on postoperative analgesia, over the use of intravenous patient controlled anesthesia (PCA, in patients undergoing fast track anesthesia during minimally invasive cardiac surgical procedures. A randomized controlled trial was undertaken after approval from local ethical committee. Written informed consent was obtained from 61 patients receiving mitral or tricuspid or both surgical valve repair in minimal invasive technique. Patients were assigned randomly to 2 groups. Group 1 received general anesthesia and intravenous patient controlled analgesia (PCA pump with Piritramide (GA group. Group 2 received a single shot of intrathecal morphine (1.5 μg/kg body weight prior to the administration of general anesthesia (ITM group. Site of puncture was confined to lumbar (L1-2 or L2-3 intrathecal space. The amount of intravenous piritramide used in post anesthesia care unit (PACU and the first postoperative day was defined as primary end point. Secondary end points included: time for tracheal extubation, pain and sedation scores in PACU upto third postoperative day. For statistical analysis Mann-Whitney-U Test and Fishers exact test (SPSS were used. We found that the demand for intravenous opioids in PACU was significantly reduced in ITM group (P <0.001. Pain scores were significantly decreased in ITM group until second postoperative day (P <0.01. There was no time delay for tracheal extubation in ITM group, and sedation scores did not differ in either group. We conclude that low dose single shot intrathecal morphine provides adequate postoperative analgesia, reduces the intravenous opioid consumption during the early postoperative period and does not defer early extubation.

  5. Antithrombotic effect of repeated doses of the ethanolic extract of ...

    African Journals Online (AJOL)

    2013-05-22

    May 22, 2013 ... extract of local olive (Olea europaea L.) leaves in rabbits. Abdallah M. ... olives have focused on olive oil and a few on olive leaves (OLEs). In this study .... thrombus was carefully removed, blotted on filter paper, and weighed ...

  6. Pharmacokinetics of rectal paracetamol after repeated dosing in children

    DEFF Research Database (Denmark)

    Hahn, T W; Henneberg, S W; Holm-Knudsen, R J

    2000-01-01

    Twenty-three children (aged between 9 weeks and 11 yr) were given paracetamol suppositories 25 mg kg-1 every 6 h (maximum 5 days) after major surgery and serum and saliva concentrations were measured. There was a good correlation (r = 0.91, P

  7. The Effects of Repeated Low-Dose Sarin Exposure

    Science.gov (United States)

    2005-08-01

    support the idea that there is a triphasic NT model for onset and progression of seizures and subsequent brain damage upon acute exposure to OP ChE...An ACh microbore column (1x530 mm ID, 10 µm UniJet, BAS #MF-8904) coupled with AChE/choline oxidase immobilized enzyme reactor (BAS # MF-8903) was...peroxidase to the electrode for the reduction of hydrogen peroxide that was generated from the immobilized enzyme reactor . The detector was set at (-)1.0

  8. Intravenous Lipids for Preterm Infants: A Review

    Directory of Open Access Journals (Sweden)

    Ghassan S. A. Salama

    2015-01-01

    Full Text Available Extremely low birth weight infants (ELBW are born at a time when the fetus is undergoing rapid intrauterine brain and body growth. Continuation of this growth in the first several weeks postnatally during the time these infants are on ventilator support and receiving critical care is often a challenge. These infants are usually highly stressed and at risk for catabolism. Parenteral nutrition is needed in these infants because most cannot meet the majority of their nutritional needs using the enteral route. Despite adoption of a more aggressive approach with amino acid infusions, there still appears to be a reluctance to use early intravenous lipids. This is based on several dogmas that suggest that lipid infusions may be associated with the development or exacerbation of lung disease, displace bilirubin from albumin, exacerbate sepsis, and cause CNS injury and thrombocytopena. Several recent reviews have focused on intravenous nutrition for premature neonate, but very little exists that provides a comprehensive review of intravenous lipid for very low birth and other critically ill neonates. Here, we would like to provide a brief basic overview, of lipid biochemistry and metabolism of lipids, especially as they pertain to the preterm infant, discuss the origin of some of the current clinical practices, and provide a review of the literature, that can be used as a basis for revising clinical care, and provide some clarity in this controversial area, where clinical care is often based more on tradition and dogma than science.

  9. Influences on physicians' choices of intravenous colloids.

    Science.gov (United States)

    Miletin, Michael S; Stewart, Thomas E; Norton, Peter G

    2002-07-01

    Controversy over the optimal intravenous fluid for volume resuscitation continues unabated. Our objectives were to characterize the demographics of physicians who prescribe intravenous colloids and determine factors that enter into their decision to choose a colloid. Questionnaire with 61 items. Ten percent ( n = 364) of frequent intravenous fluid prescribers in the province of Ontario, Canada. The response rate was 74%. Colloid use in the past year was reported by 79% of the responding physicians. Important reasons for choosing a colloid included blood loss and manipulation of oncotic pressure. Physicians tended to prefer either albumin or pentastarch, but no important reasons were found for choosing between the two. Albumin with or without crystalloid was preferred in 5/13 scenarios by more than 50% of the respondents, whereas pentastarch was not favored by more than 50% of respondents in any scenario. Physicians practising in critical care areas and teaching hospitals generally preferred pentastarch to albumin. Physicians reporting pentastarch as representing greater than 90% of total colloid use were more likely to have been visited by a drug detailer for pentastarch than those who used less synthetic colloid (54 vs 22%, p distribution. Although albumin appeared to be preferred in more clinical niches, most physicians did not state reasons for choosing between products. Marketing, specialty, location of practice and clinical scenario appear to play significant roles in the utilization of colloid products.

  10. Phase I study of intravenous iododeoxyuridine as a clinical radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Kinsella, T.J.; Russo, A.; Mitchell, J.B.; Collins, J.M.; Rowland, J.; Wright, D.; Glatstein, E.

    1985-11-01

    Twenty-four patients with locally advanced (19 patients) or metastatic (5 patients) tumors were treated in a Phase I study combining constant intravenous infusions of iododeoxyuridine (IUdR) and hyperfractionated radiation therapy. IUdR was given as a constant infusion for 12 hours/day for two separate 14-day infusion periods in most patients. The dose of IUdR was escalated from 250 to 1200 mg/m2/12-hour infusion in this study. The initial tumor volume was treated to 45 Gy/1.5 Gy BID/3 weeks followed by a cone-down boost to 20-25 Gy/1.25 Gy BID/2 weeks after a planned 2-week break. THe IUdR infusion preceded the initial and cone-down irradiation by 1 week. Local acute toxicity (within the radiation volume) was uncommon and few patients required an alteration of the planned treatment schedule. Two patients developed late local toxicity with one patient showing clinical signs of radiation hepatitis and another patient developing a large bowel obstruction that required surgical bypass. Dose-limiting systemic toxicity was confined to the bone marrow with moderate to severe thrombocytopenia developing on Day 10-14 of infusions at 1200 mg/m2/12 hours. Mild stomatitis and partial alopecia occurred in some patients at this dose level. No systemic skin toxicity was seen. Pharmacology studies revealed steady-state arterial plasma levels of IUdR of 1 to 8 X 10(-6) M over the dose range used. In vivo IUdR incorporation into tumors was studied in three patients with high-grade sarcomas using an anti-IUdR monoclonal antibody and immunohistochemistry and demonstrated incorporation in up to 50-70% of tumor cells. The preliminary treatment results, particularly in patients with unresectable sarcomas, are encouraging.

  11. Effect of intravenous 1-alpha-hydroxyvitamin D3 on secondary hyperparathyroidism in chronic uremic patients on maintenance hemodialysis

    DEFF Research Database (Denmark)

    Brandi, L; Daugaard, H; Tvedegaard, E

    1989-01-01

    The effect of intravenous 1 alpha(OH)D3 on circulating intact parathyroid hormone (PTH) and COOH-terminal immunoreactive PTH was examined in 21 patients on chronic hemodialysis. The patients were treated for 3 months with increasing doses of 1 alpha(OH)D3 under careful control of serum Ca2+. 1 al...

  12. Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Ryszard M Pluta

    Full Text Available BACKGROUND: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. METHODOLOGY: Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075 between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21-56 years were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr. Clinical, physiologic and laboratory data before, during and after infusion were analyzed. FINDINGS: The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. CONCLUSION: Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. CLINICAL TRIAL REGISTRATION INFORMATION: http

  13. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  14. Moxidectin toxicosis in a puppy successfully treated with intravenous lipids.

    Science.gov (United States)

    Crandell, Dawn E; Weinberg, Guy L

    2009-04-01

    To describe successful treatment of canine moxidectin toxicosis with the novel therapy of IV lipid administration. A 16-week-old female Jack Russell Terrier was presented with acute onset of seizures followed by paralysis and coma shortly following suspected exposure to an equine formulation of moxidectin. Moxidectin toxicity was later confirmed. Initial therapy consisted of diazepam, glycopyrrolate, and IV fluids. Mechanical ventilation and supportive nursing care were provided as needed. An emulsion of 20% soybean oil in water, commonly used as the fat component of parenteral nutrition, was administered intravenously as a bolus of 2 mL/kg followed by 4 mL/kg/h for 4 hours beginning 10 hours after exposure and was administered again at a rate of 0.5 mL/kg/min for 30 minutes beginning 25.5 hours post-exposure. Mild improvement was seen after the first dose, and dramatic improvement was noted within 30 minutes of the second dose. The puppy's neurologic status returned to normal within 6 hours of the second administration, with no relapses. IV lipid therapy is a novel treatment approach for moxidectin toxicity. Its use is supported by recent research and case studies involving IV lipid administration for bupivacaine and other fat-soluble toxins. Lipid administration appeared to reverse the signs of toxicity and may prove to be a highly effective therapy for moxidectin and other fat-soluble toxins.

  15. The Effect of Intravenous Dexmedetomidine on Spinal Block and Sedation

    Directory of Open Access Journals (Sweden)

    Abdurrahman Ekici

    2015-03-01

    Material and Methods: Our randomised, double-blind study was applied to ASA I-III, 18-75 years old 50 patients scheduled for transurethral surgery. The patients were divided into two groups and spinal anesthesia with 5% levobupivacaine 12.5 mg was administered to all patients. Intravenous dexmedetomidine was received 1 and micro;g/kg for loading dose before 0.5 and micro;g/kg/hour infusion to Group D (n=25. Saline infusion was given 1 and micro;g/kg for loading dose before 0.5 and micro;g/kg/hour infusion to Group S (n=25. Systolic, diastolic and mean arterial pressure, heart rate, peripheral oxygen saturation values, pain and sedation score, the level and duration of motor and sensorial block, recovery and patient comfort score and side effects were recorded. Results: Time to reach maximum block level and duration of spinal anesthesia were longer in Group D than Group S. Sedation scores were significantly higher in Group D than Group S intraoperatively (except 1th minute and postoperatively 10th and 15th minutes. The incidence of side effects, postoperative recovery and patient comfort values were similar between the groups. Conclusion: We found that dexmedetomidine prolongs duration of motor block, provides safe and effective sedation without increasing the incidence of side effect in the patients under spinal anesthesia. [Cukurova Med J 2015; 40(1.000: 55-62

  16. [Adult-onset Still's disease with pulmonary and cardiac involvement and response to intravenous immunoglobulin].

    Science.gov (United States)

    Neto, Nilton Salles Rosa; Waldrich, Leandro; de Carvalho, Jozélio Freire; Pereira, Rosa Maria Rodrigues

    2009-01-01

    Cardiopulmonary manifestations of adult-onset Still's disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

  17. Intravenous immunoglobulin in ABO and Rh hemolytic diseases of newborn.

    Science.gov (United States)

    Nasseri, Fatemeh; Mamouri, Gholam A; Babaei, Homa

    2006-12-01

    To evaluate whether the use of intravenous immunoglobulin in newborn infants with isoimmune hemolytic jaundice due to Rh and ABO incompatibility is an effective treatment in reducing the need for exchange transfusion. This study included all direct Coombs' test positive Rh and ABO isoimmunized babies, who admitted in the Neonatal Intensive Care Unit of Ghaem Hospital of Mashhad University of Medical Sciences, Iran, from October 2003 to October 2004. Significant hyperbilirubinemia was defined as rising by >or=0.5 mg/dl per hour. Babies were randomly assigned to received phototherapy with intravenous immunoglobulin (IVIg) 0.5 g/kg over 4 hours, every 12 hours for 3 doses (study group) or phototherapy alone (control group). Exchange transfusion was performed in any group if serum bilirubin exceeded >or=20mg/dl or rose by >or=1mg/dl/h. A total of 34 babies were eligible for this study (17 babies in each group). The number of exchange transfusion, duration of phototherapy and hospitalization days, were significant shorter in the study group versus control group. When we analyzed the outcome results in ABO and Rh hemolytic disease separately, the efficacy of IVIg was significantly better in Rh versus ABO isoimmunization. Late anemia was more common in the IVIg group 11.8% versus 0%, p=0.48. Adverse effects were not observed during IVIg administration. Administration of IVIg to newborns with significant hyperbilirubinemia due to Rh hemolytic disease reduced the need for exchange transfusion but in ABO hemolytic disease there was no significant difference between IVIg and double surface blue light phototherapy.

  18. The analgesic efficacy of intravenous lidocaine infusion after laparoscopic fundoplication: a prospective, randomized, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Dale GJ

    2016-12-01

    Full Text Available Gregory J Dale,1 Stephanie Phillips,2 Gregory L Falk3 1Westmead Hospital Clinical School, The University of Sydney, 2Sydney Adventist Hospital Clinical School, The University of Sydney, 3Concord Clinical School, The University of Sydney, Sydney, Australia Abstract: This study aimed to determine if intravenous lidocaine infusion reduces postoperative pain intensity following laparoscopic fundoplication surgery and to also validate the safety of intravenous lidocaine at the dose tested. This was an equally randomized, double-blind, placebo-controlled, parallel-group, single center trial. Adult patients undergoing laparoscopic fundoplication were recruited. The intervention group received 1 mg/kg intravenous lidocaine bolus prior to induction of anesthesia, then an intravenous infusion at 2 mg/kg/h for 24 hours. The primary outcome was pain, measured using a numeric rating scale for 30 hours postoperatively. Secondary outcomes were nausea and vomiting, opioid requirements, adverse events, serum lidocaine concentration, and length of hospital stay. The study was terminated after an interim analysis of 24 patients showed evidence of futility. There was no difference in postoperative pain scores (lidocaine versus control, mean ± standard deviation at rest (2.0 ± 2.7 vs 2.1 ± 2.4, P=0.286 or with movement (2.0 ± 2.6 vs 2.6 ± 2.7, P=0.487. Three adverse events occurred in the lidocaine group (25% of patients. Intravenous lidocaine did not provide clinically significant analgesia to patients undergoing laparoscopic fundoplication. The serum lidocaine concentration of patients who experienced adverse events were within the therapeutic range. This trial cannot confirm the safety of intravenous lidocaine at the dose tested. Keywords: analgesia, local anesthetics, intravenous infusions, pharmacokinetics

  19. Intravenous ibuprofen: the first injectable product for the treatment of pain and fever

    Directory of Open Access Journals (Sweden)

    P Brandon Bookstaver

    2010-05-01

    Full Text Available P Brandon Bookstaver, April D Miller, Celeste N Rudisill, LeAnn B NorrisDepartment of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina Campus, Columbia, South Carolina, USAAbstract: This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in a series of post-operative patient populations. Two recent studies have also noted the improvement in fever curves in critically ill and burn patients. These data, along with pharmacokinetic and pharmacologic properties, are explored in this review, which addresses the clinical utility of a parenteral NSAID in a hospitalized patient for post-operative pain management and fever reduction. Further data on intravenous ibuprofen are needed to define long-term utilization, management of acute pain, and use in special populations.Keywords: ibuprofen, intravenous, injectable, nonsteroidal anti-inflammatory drug

  20. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

    Directory of Open Access Journals (Sweden)

    Hao Jiqing

    2009-03-01

    Full Text Available Abstract Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms.

  1. Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain

    Science.gov (United States)

    Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie

    2009-01-01

    Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934

  2. Early treatment with intravenous lipid emulsion in a potentially lethal hydroxychloroquine intoxication.

    Science.gov (United States)

    Ten Broeke, R; Mestrom, E; Woo, L; Kreeftenberg, H

    2016-06-01

    This case report describes the possible benefit of intravenous lipid emulsion in two patients surviving a severe intoxication with hydroxychloroquine in a dose that was previously considered to be lethal. The first case involves a 25-year-old female who ingested 17.5 grams of hydroxychloroquine, approximately one hour before presentation. An ECG showed QRS widening and the lab results showed hypokalaemia. She became unconscious, and developed hypotension and eventually apnoea. After intubation, supportive care consisted of norepinephrine and supplementation of potassium. Moreover, sodium bicarbonate and intravenous lipid emulsion were started to prevent cardiac toxicity. After these interventions, haemodynamic stability was established within a few hours. Although cardiomyopathy was confirmed, the patient recovered after two weeks. The second case concerns a 25-year-old male who took 5 grams of hydroxychloroquine. At presentation, two hours after intake, he showed QTc prolongation and hypokalaemia. The patient was treated with the usual supportive care and, although presentation to hospital was later, with intravenous lipid emulsion. Also this patient recovered. In conclusion, these cases show the benefit of supplemental intravenous lipid emulsion to prevent cardiac toxicity after a severe intoxication with hydroxychloroquine.

  3. Intravenous acetaminophen is superior to ketamine for postoperative pain after abdominal hysterectomy: results of a prospective, randomized, double-blind, multicenter clinical trial

    Directory of Open Access Journals (Sweden)

    Faiz HR

    2014-01-01

    Full Text Available Hamid Reza Faiz,1 Poupak Rahimzadeh,1 Ognjen Visnjevac,2 Behzad Behzadi,1 Mohammad Reza Ghodraty,1 Nader D Nader2 1Iran University of Medical Sciences, Tehran, Iran; 2VA Western NY Healthcare System, University at Buffalo, Buffalo, NY, USA Background: In recent years, intravenously (IV administered acetaminophen has become one of the most common perioperative analgesics. Despite its now-routine use, IV acetaminophen's analgesic comparative efficacy has never been compared with that of ketamine, a decades-old analgesic familiar to obstetricians, gynecologists, and anesthesiologists alike. This double-blind clinical trial aimed to evaluate the analgesic effects of ketamine and IV acetaminophen on postoperative pain after abdominal hysterectomy. Methods: Eighty women aged 25–70 years old and meeting inclusion and exclusion criteria were randomly allocated into two groups of 40 to receive either IV acetaminophen or ketamine intraoperatively. Postoperatively, each patient had patient-controlled analgesia. Pain and sedation (Ramsay Sedation Scale were documented based on the visual analog scale in the recovery room and at 4 hours, 6 hours, 12 hours, and 24 hours after the surgery. Hemodynamic changes, adverse medication effects, and the need for breakthrough meperidine were also recorded for both groups. Data were analyzed by repeated-measures analysis of variance. Results: Visual analog scale scores were significantly lower in the IV acetaminophen group at each time point (P<0.05, and this group required significantly fewer doses of breakthrough analgesics compared with the ketamine group (P=0.039. The two groups had no significant differences in terms of adverse effects. Conclusion: Compared with ketamine, IV acetaminophen significantly improved postoperative pain after abdominal hysterectomy. Keywords: intravenous acetaminophen, abdominal hysterectomy, ketamine, analgesia, postoperative pain

  4. Initial experience with intravenous pentobarbital sedation for children undergoing MRI at a tertiary care pediatric hospital: the learning curve

    International Nuclear Information System (INIS)

    Greenberg, S.B.; Adams, R.C.; Aspinall, C.L.

    2000-01-01

    Objective. Our purpose is to describe the initial experience with intravenous pentobarbital sedation in children undergoing MRI at a tertiary pediatric hospital to identify errors associated with inexperience. Subjects and methods. The study included the first 100 children sedated with intravenous pentobarbital prior to magnetic resonance examination at a tertiary pediatric hospital. The protocol included a maximum dose of 6 mg/kg administered in three divided doses with the total dose not to exceed 200 mg. Flow sheets documenting vital signs, administered drug doses, and adverse reactions were maintained contemporaneous to sedation. Results. Sedation was successful in 92 children. Of the eight children who failed sedation, three were at least 12 years old and three weighed more than 50 kg. χ 2 tests identified significantly greater failure rates in children older than 11 years or weight greater than 50 kg. Two children had prolonged sedation after the maximum suggested dose was exceeded. Conclusions. The success rate was good, but could have been improved by restricting the use of pentobarbital to children less than 12 years of age and weighing less than 50 kg. Radiologists inexperienced with intravenous sedation should strictly observe the maximum suggested dose of pentobarbital to prevent prolonged sedation. (orig.)

  5. Regional cerebral energy metabolism during intravenous anesthesia with etomidate, ketamine or thiopental

    International Nuclear Information System (INIS)

    Davis, D.W.

    1987-01-01

    Regional brain glucose utilization (rCMRglc) was measured in rats during steady-state levels of intravenous anesthesia to determine if alterations in brain function due to anesthesia could provide information on the mechanisms of anesthesia. Intravenous anesthetics from three different chemical classes were studied: etomidate, ketamine and thiopental. All rCMRglc experiments were conducted in freely moving rats in isolation chambers, with the use of [6- 14 C] glucose and guantitative autoradiography. Etomidate caused a rostral-to-caudal gradient of depression of rCMRglc. The four doses of etomidate did not differ in their effects on energy metabolism. Sub-anesthetic (5 mg kg -1 ) and anesthetic (30 mg kg -1 ) doses of ketamine produced markedly different patterns of behavior. Brain energy metabolism during the sub-anesthetic dose was stimulated in most regions, while the anesthetic dose selectively stimulated the hippocampus, leaving most brain regions unaffected. Thiopental produced a dose-dependent reduction of rCMRglc in all gray matter regions. No brain region was selectively affected. Comparison of the drug-specific alterations of cerebral energy metabolism suggests these anesthetics do not act through a common mechanism. The hypothesis that each acts by binding to specific cell membrane receptors is consistent with these observations

  6. Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A. [ISRCTN75125874

    Directory of Open Access Journals (Sweden)

    Ridolfi Ruggero

    2006-02-01

    Full Text Available Abstract Background High-dose interferon alfa-2b (IFNalfa-2b, according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described. Methods Stage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m2/d intravenously (IV 5 days/week × 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm, or IFNalfa-2b 20 MU/m2/d IV 5 days/week × 4 weeks followed by 10 MU/m2 subcutaneously (SC three times per week × 48 weeks (High Dose Interferon, HDI, arm. Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle. Results The most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psichiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9% (p = 0.0074, yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m2/week was statistically higher than that delivered in the HDI arm (30.7 MU/m2/week (p = 0.003. Conclusion Four cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited.

  7. Film repeats in radiology department

    International Nuclear Information System (INIS)

    Suwan, A. Z.; Al-Shakharah, A. I

    1997-01-01

    During a one year period, 4910 radiographs of 55780 films were repeated. The objective of our study was to analyse and to classify the causes in order to minimize the repeats, cut the expenses and to provide optimal radiographs for accurate diagnosis. Analysis of the different factors revealed that, 43.6% of film repeats in our service were due to faults in exposure factors, centering comprises 15.9% of the repeats, while too much collimation was responsible for 7.6% of these repeats. All of which can be decreased by awareness and programmed training of technicians. Film blurring caused by patient motion was also responsible for 4.9% for radiographs reexamination, which can be minimized by detailed explanation to the patient and providing the necessary privacy. Fogging of X-Ray films by improper storage or inadequate handling or processing faults were responsible for 14.5% in repeats in our study. Methods and criteria for proper storage and handling of films were discussed. Recommendation for using modern day-light and laser processor has been high lighted. Artefacts are noticeably high in our cases, due to spinal dresses and frequent usage of precious metals for c osmotic purposes in this part of the world. The repeated films comprise 8.8% of all films We conclude that, the main factor responsible for repeats of up to 81.6% of cases was the technologists, thus emphasizing the importance of adequate training of the technologists. (authors). 15 refs., 9 figs., 1 table

  8. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  9. Repeated Prescribed Burning in Aspen

    Science.gov (United States)

    Donald A. Perala

    1974-01-01

    Infrequent burning weather, low flammability of the aspen-hardwood association, and prolific sprouting and seeding of shrubs and hardwoods made repeated dormant season burning a poor tool to convert good site aspen to conifers. Repeat fall burns for wildlife habitat maintenance is workable if species composition changes are not important.

  10. Systemic, pulmonary and renal haemodynamic and renal morphologic effects of intravenously infused iodixanol

    International Nuclear Information System (INIS)

    Sunnegaardh, O.; Hietala, S.O.; Holtz, E.; Nycomed A/S, Oslo

    1990-01-01

    The systemic, pulmonary and renal haemodynamic effects following an intravenous infusion (1 ml/s, 4 ml/kg) of a non-ionic isoosmolar contrast medium (iodixanol) were investigated in 8 pigs. Histopathologic changes occurring after infusion of iodixanol were studied by repeated renal biopsies. Iodixanol caused a significant increase of cardiac output, mean right atrial pressure, mean pulmonary arterial pressure, mean pulmonary arterial occlusion pressure and mean arterial pressure. There was a decrease of the systemic and pulmonary vascular resistances. Most renal biopsies showed no pathologic findings after infusion of iodixanol but in 3 specimens proteinaceous content was observed 15 min after infusion. (orig.)

  11. Mycotic aneurysms in intravenous drug abusers: the utility of intravenous digital subtraction angiography

    International Nuclear Information System (INIS)

    Shetty, P.C.; Krasicky, G.A.; Sharma, R.P.; Vemuri, B.R.; Burke, M.M.

    1985-01-01

    Two-hundred thirteen intravenous digital subtraction angiographic (DSA) examinations were performed on 195 intravenous drug abusers to rule out the possibility of a mycotic aneurysm in a groin, neck, or upper extremity infection. Twenty-three surgically proved cases of mycotic aneurysm were correctly identified with no false positive results. In addition, six cases of major venous occlusion were documented. The authors present the results of their experience and conclude that DSA is an effective and cost-efficient method of examining this high risk patient population

  12. Tevatron serial data repeater system

    International Nuclear Information System (INIS)

    Ducar, R.J.

    1981-01-01

    A ten megabit per second serial data repeater system has been developed for the 6.28km Tevatron accelerator. The repeaters are positioned at each of the thirty service buildings and accommodate control and abort system communications as well as distribution of the Tevatron time and energy clocks. The repeaters are transparent to the particular protocol of the transmissions. Serial data are encoded locally as unipolar two volt signals employing the self-clocking Manchester Bi-Phase code. The repeaters modulate the local signals to low-power bursts of 50 MHz rf carrier for the 260m transmission between service buildings. The repeaters also demodulate the transmission and restructure the data for local utilization. The employment of frequency discrimination techniques yields high immunity to the characteristic noise spectrum

  13. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  14. Repeatability of visual acuity measurement.

    Science.gov (United States)

    Raasch, T W; Bailey, I L; Bullimore, M A

    1998-05-01

    This study investigates features of visual acuity chart design and acuity testing scoring methods which affect the validity and repeatability of visual acuity measurements. Visual acuity was measured using the Sloan and British Standard letter series, and Landolt rings. Identifiability of the different letters as a function of size was estimated, and expressed in the form of frequency-of-seeing curves. These functions were then used to simulate acuity measurements with a variety of chart designs and scoring criteria. Systematic relationships exist between chart design parameters and acuity score, and acuity score repeatability. In particular, an important feature of a chart, that largely determines the repeatability of visual acuity measurement, is the amount of size change attributed to each letter. The methods used to score visual acuity performance also affect repeatability. It is possible to evaluate acuity score validity and repeatability using the statistical principles discussed here.

  15. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects.

    Directory of Open Access Journals (Sweden)

    Sebastian J Padayatty

    2010-07-01

    Full Text Available Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM practitioners. The scale of such use in the U.S. and associated side effects are unknown.We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA's Adverse Events Database. Of 199 survey respondents (out of 550, 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25 g/50 ml vials were 318,539 in 2006 and 354,647 in 2008. Manufacturers' yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study.High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit.

  16. Evaluation of the effect of intra-operative intravenous fluid on post-operative pain and pulmonary function: a randomized trial comparing 10 and 30 ml kg(-1) of crystalloid.

    LENUS (Irish Health Repository)

    Straub, B D

    2013-12-10

    Existing evidence suggests that administration of intravenous fluids has been shown to improve outcomes including pain in gynecological laparoscopic surgery but the optimum fluid dose has not been determined.

  17. Effect of intravenous esmolol on analgesic requirements in laparoscopic cholecystectomy

    Directory of Open Access Journals (Sweden)

    Ritima Dhir

    2015-01-01

    Full Text Available Background and Aims: Perioperative beta blockers are also being advocated for modulation of acute pain and reduction of intraoperative anesthetic requirements. This study evaluated the effect of perioperative use of esmolol, an ultra short acting beta blocker, on anesthesia and modulation of post operative pain in patients of laproscopic cholecystectomy. Material and Methods: Sixty adult ASA I & II grade patients of either sex, scheduled for laparoscopic cholecystectomy under general anesthesia, were enrolled in the study. The patients were randomly allocated to one of the two groups E or C according to computer generated numbers. Group E- Patients who received loading dose o