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Sample records for multiple intravenous administrations

  1. 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

  2. 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

  3. Preemptive intravenous immunoglobulin allows safe and timely administration of antineoplastic therapies in patients with multiple myeloma and parvovirus B19 disease.

    Science.gov (United States)

    Katragadda, L; Shahid, Z; Restrepo, A; Muzaffar, J; Alapat, D; Anaissie, E

    2013-08-01

    Parvovirus B19 (B19) disease is a rare cause of anemia in cancer patients and often goes unrecognized, causing delays in anticancer therapy. A retrospective review was carried out of the records of patients with multiple myeloma who underwent melphalan-based autologous stem cell transplantation (MEL-ASCT) and developed B19 infection (January 2009-December 2011). Cases were defined by the presence of clinical and laboratory findings consistent with B19 disease in patients with repeatedly positive plasma quantitative polymerase chain reaction for parvovirus. Six patients qualified as cases; 5 presented with trilineage cytopenias (chronic in 1) and 1 with anemia later progressing to pancytopenia. Transfusion-dependent thrombocytopenia led to testing in 5 patients. Two of these patients also had manifestations of autoimmune disease. Therapy with intravenous immunoglobulin (IVIG) resulted in clinical and hematologic response in all; however, 1 patient, whose white blood cell counts and serum hemoglobin levels improved, required splenectomy for persistent thrombocytopenia. All patients required additional IVIG for recurrent B19 disease. Although viral load at diagnosis did not correlate with the severity of cytopenia, its decrease was associated with response during 17 of 20 evaluable episodes (P = 0.02). Preemptive IVIG allowed the safe administration of chemotherapy in 3 patients, including MEL-ASCT in 1. Parvovirus B19 can cause severe disease in myeloma patients including ASCT recipients. Thrombocytopenia - not anemia - was the leading presentation and may be associated with autoimmune conditions. Patients with unexplained cytopenias, particularly when prolonged, should undergo testing for circulating parvovirus. A reduction in viral load was associated with response to IVIG, although additional therapy was needed for recurrent disease. Most importantly, preemptive IVIG allowed for safe and timely administration of antineoplastic therapy in patients with ongoing B

  4. Pharmacokinetic Study of Intravenous Acetaminophen Administered to Critically Ill Multiple-Trauma Patients at the Usual Dosage and a New Proposal for Administration.

    Science.gov (United States)

    Fuster-Lluch, Oscar; Zapater-Hernández, Pedro; Gerónimo-Pardo, Manuel

    2017-10-01

    The pharmacokinetic profile of intravenous acetaminophen administered to critically ill multiple-trauma patients was studied after 4 consecutive doses of 1 g every 6 hours. Eleven blood samples were taken (predose and 15, 30, 45, 60, 90, 120, 180, 240, 300, and 360 minutes postdose), and urine was collected (during 6-hour intervals between doses) to determine serum and urine acetaminophen concentrations. These were used to calculate the following pharmacokinetic parameters: maximum and minimum concentrations, terminal half-life, area under serum concentration-time curve from 0 to 6 hours, mean residence time, volume of distribution, and serum and renal clearance of acetaminophen. Daily doses of acetaminophen required to obtain steady-state minimum (bolus dosing) and average plasma concentrations (continuous infusion) of 10 μg/mL were calculated (10 μg/mL is the presumed lower limit of the analgesic range). Data are expressed as median [interquartile range]. Twenty-two patients were studied, mostly young (age 44 [34-64] years) males (68%), not obese (weight 78 [70-84] kg). Acetaminophen concentrations and pharmacokinetic parameters were these: maximum concentration 33.6 [25.7-38.7] μg/mL and minimum concentration 0.5 [0.2-2.3] μg/mL, all values below 10 μg/mL and 8 below the detection limit; half-life 1.2 [1.0-1.9] hours; area under the curve for 6 hours 34.7 [29.7-52.7] μg·h/mL; mean residence time 1.8 [1.3-2.6] hours; steady-state volume of distribution 50.8 [42.5-66.5] L; and serum and renal clearance 28.8 [18.9-33.7] L/h and 15 [11-19] mL/min, respectively. Theoretically, daily doses for a steady-state minimum concentration of 10 μg/mL would be 12.2 [7.8-16.4] g/day (166 [112-202] mg/[kg·day]); for an average steady-state concentration of 10 μg/mL, they would be 6.9 [4.5-8.1] g/day (91 [59-111] mg/[kg·day]). In conclusion, administration of acetaminophen at the recommended dosage of 1 g per 6 hours to critically ill multiple-trauma patients yields

  5. Administration costs of intravenous biologic drugs for rheumatoid arthritis

    OpenAIRE

    Soini, Erkki J; Leussu, Miina; Hallinen, Taru

    2013-01-01

    Background Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. Objectives To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs wit...

  6. Cost-minimization of mabthera intravenous versus subcutaneous administration

    NARCIS (Netherlands)

    Bax, P.; Postma, M.J.

    2013-01-01

    Objectives: To identify and compare all costs related to preparing and administrating MabThera for the intravenous and subcutaneous formulations in Dutch hematological patients. The a priori notion is that the costs of subcutaneous MabThera injections are lower compared to intravenous infusion due

  7. 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

  8. Intravenous alcohol self-administration in the P rat.

    Science.gov (United States)

    Windisch, Kyle A; Kosobud, Ann E K; Czachowski, Cristine L

    2014-08-01

    Alcohol consumption produces a complex array of effects that can be divided into two types: the explicit pharmacological effects of ethanol (which can be temporally separate from time of intake) and the more temporally "relevant" effects (primarily olfactory and taste) that bridge the time from intake to onset of the pharmacological effects. Intravenous (IV) self-administration of ethanol limits the confounding "non-pharmacological" effects associated with oral consumption, allows for controlled and precise dosing, and bypasses first order absorption kinetics, allowing for more direct and better-controlled assessment of alcohol's effect on the brain. IV ethanol self-administration has been reliably demonstrated in mouse and human experimental models; however, models of IV self-administration have been historically problematic in the rat. An operant multiple-schedule study design was used to elucidate the role of each component of a compound IV-ethanol plus oral-sucrose reinforcer. Male alcohol-preferring P rats had free access to both food and water during all IV self-administration sessions. Animals were trained to press a lever for orally delivered 1% sucrose (1S) on a fixed ratio 4 schedule, and then surgically implanted with an indwelling jugular catheter. Animals were then trained to respond on a multiple FR4-FR4 schedule composed of alternating 2.5-min components across 30-min sessions. For the multiple schedule, two components were used: an oral 1S only and an oral 1S plus IV 20% ethanol (25 mg/kg/injection). Average total ethanol intake was 0.47 ± 0.04 g/kg. We found significantly higher earning of sucrose-only reinforcers and greater sucrose-lever error responding relative to the compound oral-sucrose plus IV-ethanol reinforcer. These response patterns suggest that sucrose, not ethanol, was responsible for driving overall responding. The work with a compound IV ethanol-oral sucrose reinforcer presented here suggests that the existing intravenous ethanol

  9. Usefulness of MR cholangiopancreatography after intravenous morphine administration

    International Nuclear Information System (INIS)

    Lee, So Jung; Ko, Ji Ho; Cho, Young Duk; Jung, Mi Hee; Yoon, Byung Chull

    2007-01-01

    We wanted to assess the usefulness of MRCP after intravenous morphine administration in the evaluation of the hepatopancreatic pancreatico-biliary ductal system. We studied 15 patients who were suspected of having disease of hepatopancreatic ductal system and they did not have any obstructive lesion on ultrasonography and/or CT. MRCP was acquired before and after morphine administration (0.04 mg/kg, intravenously). Three radiologists scored the quality of the images of the anatomic structures in the hepatopancreatic ductal system. We directly compared the quality of the images obtained with using the two methods and the improvement of the artifacts by pulsatile vascular compression. The MRCP images obtained after intravenous morphine administration were better than those obtained before morphine administration for visualizing the hepatopancreatic ductal system. On direct comparison, the MRCP images obtained after morphine administration were better in 12 cases, equivocal in two cases, and the images before morphine administration were better in only one case. In three patients, MRCP before morphine injection showed signal loss at the duct across the pulsatile hepatic artery. In two of three patients, MRCP after morphine injection showed no signal loss in this ductal area. MRCP after intravenous morphine administration enables physicians to see the hepatopancreatic ductal system significantly better and the artifacts caused by pulsation of the hepatic artery can be avoided

  10. Intraosseous Administration of Antidotes in the Chemical Weapons Victim - An Alternative to the Intravenous Route

    International Nuclear Information System (INIS)

    Borron, S. W.; Arias, J. C.

    2007-01-01

    Hazardous materials paradigms call for definitive treatment of chemical victims to begin in the 'warm zone' during decontamination. This delay may result in lethal outcomes, particularly in the case of multiple victims, where rescue may be delayed due to insufficient numbers of rescue teams. It is virtually impossible for rescuers in full protective gear to establish intravenous lines. In recent years, significant advances have been made in intraosseous (IO) infusion devices. An IO device developed in our institution, the EZ-IO, is very easily placed by rescuers in typical work uniforms. IO placement takes longer while in protective gear, but is feasible. The IO is equivalent to an intravenous line, allowing more rapid administration of antidotes in the event of chemical mass casualties. Antidotes not amenable to intramuscular administration and even those often given IM may be more effective given IO. IO administration has the following possible advantages over intravenous or intramuscular antidote administration: 1. Drugs administered IO reach the vascular system virtually instantaneously. 2. IO administration may be performed in protective clothing and could theoretically be employed while awaiting rescue. 3. IO administration may be preferred over intravenous administration in the warm zone. In summary, IO administration of antidotes should be further evaluated for use in chemical disasters. The ease and speed of placement, ready access to the vascular tree, and potential for earlier intervention make it a potentially ideal means of vascular access and antidotal administration in the mass casualty situation. (author)

  11. Training requirements for the administration of intravenous contrast ...

    African Journals Online (AJOL)

    Background. The administration of intravenous contrast media (IVCM) is one of the key areas currently under investigation for inclusion in the South African (SA) radiographers' scope of practice. However, for the radiographers to legally administer IVCM, training guidelines must first be identified, developed and accredited ...

  12. Safety profile of the intravenous administration of brain-targeted stable nucleic acid lipid particles

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    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].

  13. 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.

  14. Stroke code improves intravenous thrombolysis administration in acute ischemic stroke.

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    Chih-Hao Chen

    Full Text Available Timely intravenous (IV thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with "Stroke Code" (SC may increase IV tissue plasminogen activator (tPA administration. The present study aimed to investigate the impact of SC on thrombolysis.The study period was divided into the "pre-SC era" (January 2006 to July 2010 and "SC era" (August 2010 to July 2013. Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis, stroke severity, and clinical outcomes were recorded and compared between the two eras.During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8% arrived at the emergency department within 3 h of stroke onset and 307 (5.2% received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9% to the SC era (n = 216, 33.3% (P<0.001. SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001 and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001. The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2 at discharge (49.5 vs. 39.6%, P = 0.11, with no difference in symptomatic hemorrhage events or in-hospital mortality.The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time.

  15. Pharmacokinetics of insulin following intravenous and subcutaneous administration in canines.

    Science.gov (United States)

    Ravis, W R; Comerci, C; Ganjam, V K

    1986-01-01

    Studies were conducted to examine the absorption and disposition kinetics of insulin in dogs following intravenous (IV) and subcutaneous (SC) administration of commercial preparations. After IV and SC dosing, the plasma levels were described by models which considered basal insulin level contributions. Intersubject variation in the disposition kinetics was small with half-lives of 0.52 +/- 0.05 h and total body clearances of 16.21 +/- 2.08 ml min-1 kg-1. Calculated insulin plasma secretion rates in the canines were 14.4 +/- 3.3 mUh-1 kg-1. Following SC injection of regular insulin, the rate and extent of absorption were noted to be quite variable. The absorption process appeared first-order with half-life values of 2.3 +/- 1.3 h and extents of absorption of 78 +/- 15 per cent with a range of 55-101 per cent. Insulin absorption from SC NPH preparations was evaluated as being composed of two zero-order release phases, a rapid and a slow release phase. With a dose of 1.65 U kg-1, the rapid release phase had an average duration of 1.5 h and a rate of 580 +/- 269 mUh-1 (4.2 per cent of dose) while the slow phase had a zero-order rate of 237 +/- 92 mU h-1 which continued beyond 12 h. The extent of absorption from the NPH preparation was 23.6 +/- 5.1 per cent and was significantly lower than that for the regular injection.

  16. Nonlinear pharmacokinetics of visnagin in rats after intravenous bolus administration.

    Science.gov (United States)

    Haug, Karin G; Weber, Benjamin; Hochhaus, Guenther; Butterweck, Veronika

    2012-01-23

    Ammi visnaga L. (syn. Khella, Apiaceae) preparations have traditionally been used in the Middle East for the treatment of kidney stone disease. Visnagin, a furanocoumarin derivative, is one of the main compounds of Ammi visnaga with potential effects on kidney stone prevention. To date, no information is available about the pharmacokinetic (PK) properties of visnagin. It was the aim of the study to characterize the PK properties of visnagin after intravenous (i.v.) bolus administration in rats and to develop an adequate model for the description of the observed data, including model parameter estimates. Therefore, three doses of visnagin (1.25, 2.5, and 5mg/kg) solubilized in 25% Captisol® were administered by i.v. bolus injection to male Sprague-Dawley rats. Plasma samples were extracted and subsequently analyzed using a validated LC-MS/MS method. Both non-compartmental and compartmental PK analyses were performed. A stepwise model building approach was applied including nonlinear mixed effect modeling for final model selection and to obtain final model estimates in NONMEM VI. The average areas under the curve (AUC(0-last)) after doses of 1.25, 2.5, and 5mg/kg were 1.03, 3.61, and 12.6 mg *h/l, respectively. The shape of the plasma concentration-time profiles and the observed disproportionate increase in AUC(0-last) with increasing dose suggested nonlinearity in the elimination of visnagin. A two-compartment Michaelis-Menten model provided the best fit with following typical values of the parameter estimates: 2.09 mg/(l*h) (V(max)), 0.08 mg/l (K(M)), 0.175 l (V(C)), 1.0 h⁻¹ (k₁₂), and 1.22 h⁻¹ (k₂₁). Associated inter-subject variability estimates (% CV) for V(max), K(M) and V(C) were 21.8, 70.9, and 9.2, respectively. Intra-subject variability (constant CV error model) was estimated to be 7.0%. The results suggest the involvement of a saturable process in the elimination of visnagin, possibly an enzyme or transporter system. Copyright © 2011

  17. Multiple sclerosis exceptionally presenting as parkinsonism responds to intravenous methylprednisolone.

    LENUS (Irish Health Repository)

    Saidha, S

    2012-01-31

    Parkinsonism due to multiple sclerosis (MS) is rare. In previously reported patients with MS-induced parkinsonism, MS manifested first, followed a typical clinical course, and parkinsonism developed later in the course of the illness. We report a 52-year-old male presenting with parkinsonism as the initial manifestation of MS, in whom a subsequent MS relapse consisted of marked deterioration in parkinsonism, a clinical pattern not previously described in MS. A brain MRI demonstrated involvement of the substantia nigra and basal ganglia. This patient illustrates that the clinical presentation and progression of MS may rarely be characterised by predominating parkinsonian features which are reversible by treatment with intravenous methylprednisolone and interferon beta1a.

  18. Multiple sclerosis exceptionally presenting as parkinsonism responds to intravenous methylprednisolone.

    LENUS (Irish Health Repository)

    Saidha, S

    2010-05-01

    Parkinsonism due to multiple sclerosis (MS) is rare. In previously reported patients with MS-induced parkinsonism, MS manifested first, followed a typical clinical course, and parkinsonism developed later in the course of the illness. We report a 52-year-old male presenting with parkinsonism as the initial manifestation of MS, in whom a subsequent MS relapse consisted of marked deterioration in parkinsonism, a clinical pattern not previously described in MS. A brain MRI demonstrated involvement of the substantia nigra and basal ganglia. This patient illustrates that the clinical presentation and progression of MS may rarely be characterised by predominating parkinsonian features which are reversible by treatment with intravenous methylprednisolone and interferon beta1a.

  19. Catheter indwell time and phlebitis development during peripheral intravenous catheter administration.

    Science.gov (United States)

    Pasalioglu, Kadriye Burcu; Kaya, Hatice

    2014-07-01

    Intravenous catheters have been indispensable tools of modern medicine. Although intravenous applications can be used for a multitude of purposes, these applications may cause complications, some of which have serious effects. Of these complications, the most commonly observed is phlebitis. This study was conducted to determine the effect of catheter indwell time on phlebitis development during peripheral intravenous catheter administration. This study determined the effect of catheter indwell time on phlebitis development during peripheral intravenous catheter administration. The study included a total of 103 individuals who were administered 439 catheters and satisfied the study enrollment criteria at one infectious diseases clinic in Istanbul/Turkey. Data were compiled from Patient Information Forms, Peripheral Intravenous Catheter and Therapy Information Forms, reported grades based on the Visual Infusion Phlebitis Assessment Scale, and Peripheral Intravenous Catheter Nurse Observation Forms. The data were analyzed using SPSS. Results : The mean patient age was 53.75±15.54 (standard deviation) years, and 59.2% of the study participants were men. Phlebitis was detected in 41.2% of peripheral intravenous catheters, and the rate decreased with increased catheter indwell time. Analyses showed that catheter indwell time, antibiotic usage, sex, and catheterization sites were significantly associated with development of phlebitis. The results of this study show that catheters can be used for longer periods of time when administered under optimal conditions and with appropriate surveillance.

  20. Intravenous administration of puppy deciduous teeth stem cells in degenerative valve disease

    Directory of Open Access Journals (Sweden)

    Soontaree Petchdee

    2016-12-01

    Full Text Available Aim: The objective of this study is to investigate the improvement of heart function in dogs with chronic valvular heart disease after puppy deciduous teeth stem cells (pDSCs administration. Materials and Methods: 20 client-owned dogs with degenerative valvular heart disease underwent multiple intravenous injections of allogeneic pDSCs. Dogs were randomly assigned to two groups: (i Control group (n=10 with standard treatment for heart failure and (ii group with standard treatment and multiple administrations of pDSCs (n=10. Electrocardiography, complete transthoracic echocardiography, thoracic radiography, and blood pressure were recorded before and after pDSCs injections for 15, 30 and 60 days. Results: Post pDSCs injection showed measurable improvement in left ventricular ejection fraction, American College of Veterinary Internal Medicine (ACVIM functional class significantly improved and improved quality of life scores were observed. In the control group, there were no significant enhancements in heart function or ACVIM class. Conclusions: This finding suggests that pDSCs could be a supplement for valvular heart disease treatment.

  1. Intravenous Iron Administration and Hypophosphatemia in Clinical Practice

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    S. Hardy

    2015-01-01

    Full Text Available Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA and iron deficiency (ID. Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM- related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32–0.80 mmol/L or severe (<0.32 mmol/L hypophosphatemia were questioned for symptoms. Results. During the study period, 234 patients received iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM (p=0.04 but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed.

  2. A systematic review and meta-analysis comparing combined intravenous and topical tranexamic acid with intravenous administration alone in THA.

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    Yangbai Sun

    Full Text Available To compare the effectiveness and safety of combined intravenous and topical tranexamic acid with intravenous use alone in THA.The electronic databases MEDLINE, EMBASE, BIOSIS, Cochrane central, and further adapted for Google and Google Scholar internet, last updated on Dec 30, 2016, were searched. Evaluated outcomes included total blood loss, transfusion rate, maximum postoperative Hb drop, and incidence of thromboembolic complications. The standard mean difference (SMD or the relative risk (RR was calculated for continuous or dichotomous data respectively. The quality of the trial was assessed, and meta-analyses were performed with the Cochrane Collaboration's RevMan 5.0 software.Five RCTs with 457 patients were included. Combined TXA administration reduced blood loss (SMD, 1.39; 95%CI, 0.55 to 2.23; P<0.00001, I2 = 94%, hemoglobin decline (SMD, 0.84; 95%CI, 0.13 to 1.54; P = 0.01, I2 = 83% and the need for transfusion (RR, 2.58; 95%CI, 1.59 to 4.18; P = 0.65, I2 = 0% without increasing the rate of thromboembolic complications significantly (RR, 0.83; 95%CI, 0.27 to 2.54; P = 0.81, I2 = 0%.The present study has emphasized that combined TXA administration can effectively reduce blood loss, hemoglobin decline and the need for transfusion without increasing the rate of thromboembolic complications.

  3. 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.

  4. Real-Time Scintigraphic Assessment of Intravenous Radium-223 Administration for Quality Control

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    Chadwick L. Wright

    2015-01-01

    Full Text Available Radium-223 (223Ra dichloride is an approved intravenous radiotherapy for patients with osseous metastases from castration-resistant prostate cancer (CRPC. In addition to the therapeutic alpha radiation, there is additional 223Ra radiation generated which produces photons that can be imaged with conventional gamma cameras. No studies have evaluated real-time and quality imaging during intravenous 223Ra administration to verify systemic circulation and exclude 223Ra extravasation at the injection site. A retrospective review was performed for fifteen 223Ra administrations for CRPC patients which were imaged using a large field of view portable gamma camera (LFOVPGC for the purposes of quality control and patient safety. Dynamic imaging of the chest was performed before, during, and after the 223Ra administration to verify systemic circulation, per institutional clinical protocol. Before and after 223Ra administration, a static image was obtained of the intravenous access site. Dynamic imaging of the chest confirmed systemic administration early during the 1-minute injection period for all patients. There were no cases of focal 223Ra extravasation at the site of intravenous access. These results verify that systemic 223Ra administrations can be quantified with real-time imaging using an LFOVPGC. This simple approach can confirm and quantify systemic circulation of 223Ra early during injection and exclude focal extravasation for the purposes of quality control.

  5. Physiologic effects of intravenous fluid administration in healthy volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Jensen, Peter; Kehlet, Henrik

    2003-01-01

    , infusion of the fluid over 3 h in the morning, and additionally 24-h hospitalization under standardized conditions. Primary outcome assessments were pulmonary function (spirometry), exercise capacity (submaximal treadmill test), balance function (BalanceMaster), and weight. Infusion of 40 mL/kg of lactated...... by fluid administration. These findings may serve as a basis for clinical studies applying the same type of fluid in different amounts to determine the optimal amount of perioperative fluid in various surgical procedures. IMPLICATIONS: Infusion of 40 mL/kg of lactated Ringer's solution in volunteers led...

  6. Physiologic effects of intravenous fluid administration in healthy volunteers

    DEFF Research Database (Denmark)

    Holte, Kathrine; Jensen, Peter; Kehlet, Henrik

    2003-01-01

    Dose regimens in perioperative fluid management are rarely evidence based. Therefore, we investigated responses to an IV fluid infusion in healthy volunteers to assess basic physiologic effects of a fluid infusion per se. In a prospective, double-blinded, cross-randomized study, 12 healthy...... volunteers with a median age of 63 yr (range, 59-67 yr) received an infusion of lactated Ringer's solution 40 mL/kg (median, 2820 mL) or 5 mL/kg (median, 353 mL; background infusion) in random order on two separate occasions. The study was designed to mimic the perioperative course with preoperative fasting...... by fluid administration. These findings may serve as a basis for clinical studies applying the same type of fluid in different amounts to determine the optimal amount of perioperative fluid in various surgical procedures. IMPLICATIONS: Infusion of 40 mL/kg of lactated Ringer's solution in volunteers led...

  7. Comparison of the pharmacokinetics of imipenem after intravenous and intrathecal administration in rabbits.

    Science.gov (United States)

    Wang, Y; Qiu, L; Dong, J; Wang, B; Shi, Z; Liu, B; Wang, W; Zhang, J; Cai, S; Ye, G; Cai, X

    2013-03-01

    Intrathecal administration of antibiotics has potentially high effectiveness for the treatment for severe intracranial infections, particularly nosocomial meningitis. The use of intrathecal injection of antibiotics has been reported mostly in case reports. However, there is sparse data regarding the pharmacokinetics of antibiotics after intrathecal administration. This study investigated whether intrathecal injection is an effective method for the administration of imipenem. The pharmacokinetics of imipenem after intrathecal and intravenous administration of 1:1 imipenem: cilastatin (IMI/CIL) to rabbits were compared. The AUC0-t in the cerebrospinal fluid for intrathecal administration was approximately twice that of an equal dose of intravenous administration at doses of 0.35, 0.7, and 1.4 mg/kg. Brain concentrations of imipenem after intrathecal injection were three times greater than observed after intravenous injection and remained high for at least 8 hours post-injection. Elimination of imipenem after administration by either route was primarily via urine, but a transient surge of imipenem in bile and intestinal tissue was observed. Results indicate that there is a clinical potential for intrathecally administered IMI/CIL. Further studies are warranted to investigate the potential for seizure and to assess the translatability of the rabbit model to human treatment.

  8. Errors and discrepancies in the administration of intravenous infusions: a mixed methods multihospital observational study

    OpenAIRE

    Lyons, I.; Furniss, D.; Blandford, A.; Chumbley, G.; Iacovides, I.; Wei, L.; Cox, A.; Mayer, A.; Vos, J.; Galal-Edeen, G. H.; Schnock, K. O.; Dykes, P. C.; Bates, D. W.; Franklin, B. D.

    2018-01-01

    INTRODUCTION: Intravenous medication administration has traditionally been regarded as error prone, with high potential for harm. A recent US multisite study revealed few potentially harmful errors despite a high overall error rate. However, there is limited evidence about infusion practices in England and how they relate to prevalence and types of error. OBJECTIVES: To determine the prevalence, types and severity of errors and discrepancies in infusion administration in English hospitals, an...

  9. The pharmacokinetics of L-tryptophan following its intravenous and oral administration.

    OpenAIRE

    Green, A R; Aronson, J K; Cowen, P J

    1985-01-01

    The pharmacokinetics of L-tryptophan (5 g and 7.5 g) have been studied after its intravenous administration to healthy subjects and the results compared with those obtained after oral administration (0.7 g-3.5 g). In order to do this, we have re-analysed previously published data relating to oral administration. The data obtained following the oral administration of L-tryptophan suggest that the total body clearance and apparent volume of distribution are saturable. The pharmacokinetics of tr...

  10. Does intravenous administration of recombinant tissue plasminogen activator for ischemic stroke can cause inferior myocardial infarction?

    Directory of Open Access Journals (Sweden)

    Mostafa Almasi

    2016-06-01

    Full Text Available Recombinant tissue plasminogen activator (rTPA is one of the main portions of acute ischemic stroke management, but unfortunately has some complications. Myocardial infarction (MI is a hazardous complication of administration of intravenous rTPA that has been reported recently. A 78-year-old lady was admitted for elective coronary artery bypass graft surgery. On the second day of admission, she developed acute left hemiparesis and intravenous rTPA was administered within 120 minutes. Three hours later, she has had chest pain. Rescue percutaneous coronary intervention was performed on right coronary artery due to diagnosis of inferior MI, and the symptoms were resolved.

  11. Errors in the administration of intravenous medications in hospital and the role of correct procedures and nurse experience

    OpenAIRE

    Westbrook, Johanna I; Rob, Marilyn I; Woods, Amanda; Parry, Dave

    2011-01-01

    Background Intravenous medication administrations have a high incidence of error but there is limited evidence of associated factors or error severity. Objective To measure the frequency, type and severity of intravenous administration errors in hospitals and the associations between errors, procedural failures and nurse experience. Methods Prospective observational study of 107 nurses preparing and administering 568 intravenous medications on six wards across two teaching hospitals. Procedur...

  12. Effects of albendazole nanoparticles in mice with hepatic echinococosis: Portal vein cannulation versus intravenous administration.

    Science.gov (United States)

    Zhu, Di-Wen; Zhang, Ming-Xing; Bao, Ying-Jun; Gu, Jun-Peng; Ji, Wei-Zheng; Zhang, Hai-Xiao; Ren, Wei-Xin

    2015-07-01

    To compare the ABZ and its metabolites concentration in cyst tissue of hepatic alveolar echinococcosis administered by different routes, forty male Wistar rats receiving albendazole nanoparticles from tail vein and portal vein were divided into two groups, the concentration of ABZ and its metabolites ABZSO, ABZSO2, in the cyst tissue, were analyzed by HPLC at 2, 4, 8, 24, 36 h after administration. The parent drug and its metabolites were detected in plasm and the cyst tissue after portal cannulation and intravenous administration. The last results were the concentration of ABZ in the portal cannulation group was higher than in the intravenous group at every time point (p < 0.05). Compared to the intravenous group, the portal cannulation administration of ABZ led to a lower plasm concentration of ABZ. The concentration of ABZ and the active ABZSO were significantly higher in the portal cannulation group than that of the intravenous group. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Costs of subcutaneous and intravenous administration of trastuzumab for patients with HER2-positive breast cancer

    DEFF Research Database (Denmark)

    Olsen, Jens; Jensen, Kenneth Forsstrøm; Olesen, Daniel Sloth

    2018-01-01

    AIM: Trastuzumab is available in an intravenous (iv.) and a subcutaneous (sc.) formulation. The objective of this study was to estimate the costs of administration of iv. and sc. trastuzumab treatment. MATERIALS & METHODS: Via interviews, we identified all the activities associated with iv. and sc....... administration. The outcome was time estimates. To estimate the administration costs, the time estimates were valued by average gross wages. RESULTS: The iv. administration takes longer time as infusion time is longer (25 or 85 min). The iv. administration is associated with higher cost for 17 cycles; €971...... (€1858 vs €887). CONCLUSION: sc. administration is associated with lower administration costs. Switching patients from iv. to sc. would make it possible to treat more patients without increasing the personnel resources....

  14. 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.

  15. Pharmacokinetics and skin concentrations of lincomycin after intravenous and oral administration to cats

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    Gabriela A. Albarellos

    2013-10-01

    Full Text Available The aim of the present study was to describe the plasma pharmacokinetic profile and skin concentrations of lincomycin after intravenous administration of a 15% solution and oral administration of 300 mg tablets at a dosing rate of 15 mg/kg to cats. Susceptibility of staphylococci (n = 31 and streptococci (n = 23 strains isolated from clinical cases was also determined. Lincomycin plasma and skin concentrations were determined by microbiological assay using Kocuria rhizophila ATCC 9341 as test microorganism. Susceptibility was established by the antimicrobial disc diffusion test. Individual lincomycin plasma concentration–time curves were analysed by a non-compartmental approach. After intravenous administration, volume of distribution, body clearance and elimination half-life were 0.97 L/kg ± 0.15 L/kg, 0.17 L/kg ± 0.06 L/h.kg and 4.20 h ± 1.12 h, respectively. After oral administration, peak plasma concentration, time of maximum plasma concentration and bioavailability were 22.52 µg/mL ± 10.97 µg/mL, 0.80 h ± 0.11 h and 81.78% ± 24.05%, respectively. Two hours after lincomycin administration, skin concentrations were 17.26 µg/mL ± 1.32 µg/mL (intravenous and 16.58 µg/mL ± 0.90 µg/mL (oral. The corresponding skin: plasma ratios were 2.08 ± 0.47 (intravenous and 1.84 ± 0.97 (oral. The majority of staphylococci and streptococci tested in this study were susceptible to lincosamides (87.09% and 69.56%, respectively. In conclusion, lincomycin administered orally at the assayed dose showed a good pharmacokinetic profile, with a long elimination half-life and effective skin concentration. Therefore, it could be a good first option for treating skin infections in cats.

  16. Comparison between intravenous and intramuscular administration of ketamine in children sedation referred to emergency department

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    Behnaz Boroumand Rezazadeh

    2014-12-01

    Full Text Available Ketamine, among wide variety of sedative drugs, has shown beneficial effects when using during the procedural sedation, specifically in pediatrics. Various parameters should be considered in order to perform a safe and effective procedural sedation including optimum dosage of the sedative, administration methods of sedation, and need for applying any adjuvant drug. In this study, we aimed to review the studies, which have compared the efficacy of the different ways of the injection of ketamine such as intravenous or intramuscular ketamine application. Based on data obtained from the related articles, efficacy and safety of these two methods of ketamine usage in the pediatric procedural sedation were widely similar, but the intravenously administration of the ketamine can be proposed as the preferable mode.

  17. Intravenous or oral administration of vinorelbine in adjuvant chemotherapy with cisplatin and vinorelbine for resected NSCLC

    DEFF Research Database (Denmark)

    Sorensen, Steffen Filskov; Carus, Andreas; Meldgaard, Peter

    2015-01-01

    OBJECTIVES: Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early-stage NSCLC. Vinorelbine can also be administered orally. However, the efficacy of orally administrated vinorelbine in adjuvant treatment of NSCLC is unknown. We...... University Hospital (Denmark) from 2005 to 2012 for adjuvant chemotherapy after surgery for NSCLC. RESULTS AND CONCLUSION: Of the 265 patients included in this study, 126 patients received i.v. and 139 received p.o. vinorelbine/cisplatin. The two groups were comparable with respect to important baseline....... In conclusion we observed that intravenous or oral administration of vinorelbine in combination with cisplatin after surgery for NSCLC appear equally effective in terms of overall and disease-free survival....

  18. Persistent renal enhancement after intra-arterial versus intravenous iodixanol administration

    International Nuclear Information System (INIS)

    Chou, Shinn-Huey; Wang, Zhen J.; Kuo, Jonathan; Cabarrus, Miguel; Fu Yanjun; Aslam, Rizwan; Yee, Judy; Zimmet, Jeffrey M.; Shunk, Kendrick; Elicker, Brett; Yeh, Benjamin M.

    2011-01-01

    Purpose: To examine the clinical significance of persistent renal enhancement after iodixanol administration. Methods: We retrospectively studied 166 consecutive patients who underwent non-enhanced abdominopelvic CT within 7 days after receiving intra-arterial (n = 99) or intravenous (n = 67) iodixanol. Renal attenuation was measured for each non-enhanced CT scan. Persistent renal enhancement was defined as CT attenuation >55 Hounsfield units (HU). Contrast-induced nephropathy (CIN) was defined as a rise in serum creatinine >0.5 mg/dL within 5 days after contrast administration. Results: While the intensity and frequency of persistent renal enhancement was higher after intra-arterial (mean CT attenuation of 73.7 HU, seen in 54 of 99 patients, or 55%) than intravenous contrast material administration (51.8 HU, seen in 21 of 67, or 31%, p < 0.005), a multivariate regression model showed that the independent predictors of persistent renal enhancement were a shorter time interval until the subsequent non-enhanced CT (p < 0.001); higher contrast dose (p < 0.001); higher baseline serum creatinine (p < 0.01); and older age (p < 0.05). The route of contrast administration was not a predictor of persistent renal enhancement in this model. Contrast-induced nephropathy was noted in 9 patients who received intra-arterial (9%) versus 3 who received intravenous iodixanol (4%), and was more common in patients with persistent renal enhancement (p < 0.01). Conclusion: Persistent renal enhancement at follow-up non-contrast CT suggests a greater risk for contrast-induced nephropathy, but the increased frequency of striking renal enhancement in patients who received intra-arterial rather than intravenous contrast material also reflects the larger doses of contrast and shorter time to subsequent follow-up CT scanning for such patients.

  19. Costs Associated with Intravenous Cancer Therapy Administration in Patients with Metastatic Soft Tissue Sarcoma in a US Population

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    Mei Sheng Duh

    2013-01-01

    Full Text Available Background. The most common chemotherapies in metastatic soft tissue sarcoma (mSTS require intravenous (IV administration. This often requires patients to make multiple outpatient visits per chemotherapy cycle, possibly impeding patients’ daily activities and increasing caregiver burden and medical costs. This study investigated costs associated with IV cancer therapy administration in mSTS from the payer perspective of the health care system. Patients and Methods. From the Experian Healthcare database, 1,228 mSTS patients were selected. Data were analyzed on outpatient visits during 2005–2012 involving IV cancer therapy administration. Costs were estimated on a per patient per visit (PPPV and per patient per month (PPPM basis. Results. The mean (median cost of IV therapy was $2,427 ($1,532 PPPV and $5,468 ($4,310 PPPM, of which approximately 60% was IV drug costs. IV administration costs averaged $399 PPPV and $900 PPPM, representing 16.5% of total visit costs. Anthracycline and alkylating-agents-based therapies had the highest PPPV and PPPM IV administration costs, respectively (mean $479 and $1,336, resp.. Patients with managed care insurance had the highest IV administration costs (mean $504 PPPV; $1,120 PPPM. Conclusions. IV administration costs constitute a considerable proportion of the total costs of receiving an IV cancer therapy to treat mSTS.

  20. Pharmacokinetics of oxiracetam and its degraded substance (HOPAA after oral and intravenous administration in rats

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    Xinhuan Wan

    2014-12-01

    Full Text Available The pharmacokinetics of oxiracetam and its degraded substance (4-hydroxy-2-oxo-1-pyrrolidine acetic acid, HOPAA after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method. Three groups of rats after an overnight fasted received 10 g/kg (n = 6 oxiracetam suspensions orally, and 2 g/kg (n = 6 normal or degraded oxiracetam injections intravenously via a caudal tail vein, respectively. Before the pharmacokinetic experiment, a simple safety evaluation test was conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice. There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within two weeks, demonstrating that HOPAA was non-toxic in mice. Following intravenous administration of the normal injections, the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase. The values of t1/2 were 3.1 ± 1.5 h for oxiracetam and 0.8 ± 0.2 h for HOPAA, and the mean residence times (MRT were 1.2 ± 0.1 h and 0.8 ± 0.1 h, respectively. Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections. Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes, and both had a longer t1/2 and MRT than those of intravenous administration. Contents of HOPAA in three groups were calculated based on AUC0–t values of the two analytes. The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetam at the same time for every group. Additionally, the values of absolute bioavailability of oxiracetam were about 8.0% and 7.4% calculated by the normal or degraded oxiracetam injections, which were far less than the value of 75% reported in literature, indicating the necessity of further study.

  1. Mercury poisoning through intravenous administration: Two case reports with literature review.

    Science.gov (United States)

    Lu, Qiuying; Liu, Zilong; Chen, Xiaorui

    2017-11-01

    Metallic mercury poisoning through intravenous injection is rare, especially for a homicide attempt. Diagnosis and treatment of the disease are challenging. A 34-year-old male presented with pyrexia, chill, fatigue, body aches, and pain of the dorsal aspect of right foot. Another case is that of a 29-year-old male who committed suicide by injecting himself metallic mercury 15 g intravenously and presented with dizzy, dyspnea, fatigue, sweatiness, and waist soreness. The patient's condition in case 1 was deteriorated after initial treatment. Imaging studies revealed multiple high-density spots throughout the body especially in the lungs. On further questioning, the patient's girlfriend acknowledged that she injected him about 40 g mercury intravenously 11 days ago. The diagnosis was then confirmed with a urinary mercury concentration of 4828 mg/L. Surgical excision, continuous blood purification, plasma exchange, alveolar lavage, and chelation were performed successively in case 1. Blood irrigation and chelation therapy were performed in case 2. The laboratory test results and organ function of the patient in case 1 gradually returned to normal. However, in case 2, the patient's dyspnea was getting worse and he finally died due to toxic encephalopathy and respiratory failure. Early diagnosis and appropriate treatment are critical for intravenous mercury poisoning. It should be concerned about the combined use of chelation agents and other treatments, such as surgical excision, hemodialysis and plasma exchange in clinical settings.

  2. Informed consent for the administration of an intravenous contrast agent: importance and determinants of patient refusal

    International Nuclear Information System (INIS)

    Martel, J.; Garcia-Diaz, J. D.

    1999-01-01

    We proposed to determine the proportion of patients who refuse to undergo intravenous contrast administration and the factors that influence their refusal. Our series consisted of 442 patients who were supposed to undergo imaging studies involving the intravenous injection of an iodine contrast. In a personal interview, the patients were issued a questionnaire specifically designed for this study. The following parameters were recorded: sex, age, inpatient or outpatient status, medical history available, person who informed them about the procedure, person signing the informed consent (patient or other) , highest academic degree, attitude toward receiving the information and degree of concern after reading and signing the consent form. In our series 8.6% of the patients (95% confidence interval: 6-11.2) refused to sign the informed consent form. In addition, there were a number of patients who delayed the procedure or hindered the daily work schedule by some other means. When the relationship between each of the variables studied and refusal to sign the consent form was assessed, significant associations were observed between the latter and the academic level of the patient, his or her degree of concern and having received the information from a trained person. There was also a nearly significant trend toward the association between refusal and the patient's background. Relatively few patients refuse to sign the informed consent to receive intravenous contrast administration but this negative decision interferes with the health care practice. It is possible to identify certain correctable factors that influence the patient in this respect. (Author) 13 refs

  3. Intravenous Vitamin C administration reduces fatigue in office workers: a double-blind randomized controlled trial

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    Suh Sang-Yeon

    2012-01-01

    Full Text Available Abstract Background Studies of the efficacy of vitamin C treatment for fatigue have yielded inconsistent results. One of the reasons for this inconsistency could be the difference in delivery routes. Therefore, we planned a clinical trial with intravenous vitamin C administration. Methods We evaluated the effect of intravenous vitamin C on fatigue in office workers. A group of 141 healthy volunteers, aged 20 to 49 years participated in this randomized, double-blind, controlled clinical trial. The trial group received 10 grams of vitamin C with normal saline intravenously, while the placebo group received normal saline only. Since vitamin C is a well-known antioxidant, oxidative stress was measured. Fatigue score, oxidative stress, and plasma vitamin C levels were measured before intervention, and again two hours and one day after intervention. Adverse events were monitored. Results The fatigue scores measured at two hours after intervention and one day after intervention were significantly different between the two groups (p = 0.004; fatigue scores decreased in the vitamin C group after two hours and remained lower for one day. Trial also led to higher plasma vitamin C levels and lower oxidative stress compared to the placebo group (p Conclusion Thus, intravenous vitamin C reduced fatigue at two hours, and the effect persisted for one day. There were no significant differences in adverse events between two groups. High dose intravenous vitamin C proved to be safe and effective against fatigue in this study. Trial Registration The clinical trial registration of this trial is http://ClinicalTrials.govNCT00633581.

  4. 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

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

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    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

  6. Intravenous Administration of Lycopene, a Tomato Extract, Protects against Myocardial Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Tong, Chao; Peng, Chuan; Wang, Lianlian; Zhang, Li; Yang, Xiaotao; Xu, Ping; Li, Jinjin; Delplancke, Thibaut; Zhang, Hua; Qi, Hongbo

    2016-03-03

    Oral uptake of lycopene has been shown to be beneficial for preventing myocardial ischemia-reperfusion (I/R) injury. However, the strong first-pass metabolism of lycopene influences its bioavailability and impedes its clinic application. In this study, we determined an intravenous (IV) administration dose of lycopene protects against myocardial infarction (MI) in a mouse model, and investigated the effects of acute lycopene administration on reactive oxygen species (ROS) production and related signaling pathways during myocardial I/R. In this study, we established both in vitro hypoxia/reoxygenation (H/R) cell model and in vivo regional myocardial I/R mouse model by ligating left anterior artery descending. TTC dual staining was used to assess I/R induced MI in the absence and presence of acute lycopene administration via tail vein injection. Lycopene treatment (1 μM) before reoxygenation significantly reduced cardiomyocyte death induced by H/R. Intravenous administration of lycopene to achieve 1 μM concentration in circulating blood significantly suppressed MI, ROS production, and JNK phosphorylation in the cardiac tissue of mice during in vivo regional I/R. Elevating circulating lycopene to 1 μM via IV injection protects against myocardial I/R injury through inhibition of ROS accumulation and consequent inflammation in mice.

  7. Pharmacokinetics of ketoprofen enantiomers following intravenous and oral administration to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, Heather K; Arthur, Rick M; Steinmetz, Stacy; McKemie, Dan S

    2016-01-01

    Ketoprofen (KTP) is currently only available as an injectable formulation for intravenous administration to horses. The primary goal of the study reported here was to characterize the pharmacokinetics of KTP, including determination of bioavailability following oral administration of the currently available injectable formulation as well as a paste formulation. KTP was administered intravenously and orally, and blood and urine samples were collected at various time points up to 96 h. KTP enantiomer concentrations were determined using LC–MS/MS, and pharmacokinetic analyses were performed. Mean ± standard error values for systemic clearance, steady state volume of distribution and terminal elimination half-life were 0.345 ± 0.033 [R(−) KTP] and 0.167 ± 0.016 [S(+) KTP] L/kg/h, 0.344 ± 0.044 [R(−) KTP] and 0.298 ± 0.025 [S(+) KTP] L/kg, and 2.49 ± 0.077 [R(−) KTP] and 2.86 ± 0.102 [S(+) KTP] h, respectively. Oral bioavailability was calculated as 69.5 ± 10.3% and 88.2 ± 15.9% for R(−) KTP and S(+) KTP, respectively, following administration of the injectable formulation and 53.0 ± 6.0 and 53.0 ± 16.0% for the R(−) KTP and S(+) KTP, respectively, following administration of KTP paste.

  8. 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

  9. Is intraarticular administration of tranexamic acid better than its intravenous administration in reducing blood loss after total knee arthroplasty?

    Directory of Open Access Journals (Sweden)

    Ameet Pispati

    2013-01-01

    Full Text Available Context: It has been well-established now that intravenous (IV tranexamic acid (TXA is a potent agent to control postoperative blood loss following total knee arthroplasty (TKA. Recently, intraarticular administration of this agent has also shown good efficacy for the same. Aims: Comparison of postoperative blood loss between IV and topical administration of TXA in TKAs. Materials and Design: Eighty-six TKAs on knees were included in this study. Randomization was done so that 40 TKA received 1 g of IV TXA, while 46 had intraarticular administration of 1 g TXA. Subjets and Methods: We compared the postoperative blood loss by calculating the difference in pre- and postop hemoglobin and need for blood transfusion. Functional assessment was done on basis of Western Ontario McMaster Osteo-Arthritis Index (WOMAC scores and complications like postoperative infection, oozing from the wound site and thromboembolic manifestations. Results: Blood loss was significantly less in the intraarticular administration group as compared to the IV injection group. Total blood loss, blood transfusion group, and drain output was also less but the difference was not significant. The functional assessment (WOMAC scores were equivocal and so were the complications including thromboembolic manifestations (two cases each of deep vein thrombosis (DVT and no cases of pulmonary embolism (PE. Conclusion: Intraarticular administration of TXA to prevent postoperative blood loss in TKA is a safe and effective alternative/adjunct to its IV administration.

  10. Pharmacokinetics of /sup 3/H-pipethiaden after single oral and intravenous administration in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lapka, R.; Franc, Z.; Smolik, S.

    1985-01-01

    Tritium labelled anti-migraine drug 4-(1-methyl-4-piperidyliden)-4,9-duhydrothieno(2,3-c)-2-benzothiepine (pipethiaden) was prepared. After oral and intravenous administration to rats not only the courses of total radioactivity in plasma and various organs were determined, but by means of TLC-radiometry also the levels of pipethiaden itself. After the oral dose 1.35 mg/kg the plasma levels of pipethiaden did not exceed 3.5 ng/ml. Some pharmacokinetic parameters (e.g. t/sub 1/2/el-4h) were calculated by compartmental analysis of plasma levels.

  11. Wheel-running attenuates intravenous cocaine self-administration in rats: sex differences.

    Science.gov (United States)

    Cosgrove, Kelly P; Hunter, Robb G; Carroll, Marilyn E

    2002-10-01

    This experiment examines the effect of access to a running-wheel on intravenous cocaine self-administration in male and female rats. Rats maintained at 85% of their free-feeding body weight were first exposed to the running-wheel alone during the 6-h sessions until behavior stabilized for 14 days. Intravenous cannulae were then implanted, and the rats were trained to self-administer a low dose of cocaine (0.2 mg/kg) under a fixed-ratio (FR 1) schedule during the 6-h sessions, while the wheel remained inactive and cocaine self-administration stabilized (cocaine-only condition). Next, the wheel access and cocaine self-administration were concurrently available followed by a period of cocaine-only. Behavior was allowed to stabilize for 10 days at each phase. During wheel access, cocaine infusions decreased by 21.9% in males and 70.6% in females compared to the cocaine-only condition; the effect was statistically significant in females. Infusions increased to baseline levels when wheel access was terminated. When cocaine infusions were concurrently available, wheel revolutions were reduced by 63.7% and 61.5% in males and females, respectively, compared to the wheel-only condition. This result did not differ due to sex, but it was statistically significant when data from males and females were combined. These results indicate that wheel-running activity had a greater suppressant effect on cocaine self-administration in females than in males, and in females, wheel-running and cocaine self-administration are substitutable as reinforcers.

  12. First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial.

    Science.gov (United States)

    Rigby-Jones, Ann E; Sneyd, J Robert; Vijn, Peter; Boen, Patrick; Cross, Maurice

    2010-06-29

    Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics.

  13. Intravenous clonidine administration and its ability to reduce pulmonary arterial pressure in patients undergoing heart surgery

    Directory of Open Access Journals (Sweden)

    Benedito Barbosa João

    2014-01-01

    Full Text Available Objective: Evaluate the ability of clonidine to reduce pulmonary arterial pressure in patients with pulmonary hypertension undergoing heart surgery, either by reducing the pressure values from the direct measurement of pulmonary arterial pressure or by reducing or eliminating the need for intraoperative dobutamine and nitroprusside. Method: Randomized, double-blind, placebo-controlled, comparative study conducted in 30 patients with pulmonary arterial hypertension type 2 undergoing cardiac surgery. Mean pulmonary arterial pressure and dosage of dobutamine and sodium nitroprusside were assessed four times: before intravenous administration of clonidine (2 μg/kg or placebo (T0, 30 min after tested treatment and before cardiopulmonary bypass (T1, immediately after CPB (T2, 10 min after protamine injection (T3. Results: There were no significant differences regarding mean pulmonary arterial pressure at any time of evaluation. There was no significant difference between groups regarding other variables, such as mean systemic arterial pressure, heart rate, total dose of dobutamine, total dose of sodium nitroprusside, and need for fentanyl. Conclusion: Data analysis from patients included in this study allows us to conclude that intravenous clonidine (2 μg/kg was not able to reduce the mean pulmonary arterial pressure in patients with pulmonary hypertension in group 2 (pulmonary venous hypertension, undergoing heart surgery, or reduce or eliminate the need for intraoperative administration of dobutamine and sodium nitroprusside. Keywords: Clonidine, Pulmonary hypertension, Heart surgery

  14. [Renal response to intravenous administration of sodium bicarbonate in newborn infants of different gestational ages].

    Science.gov (United States)

    Jasso-Gutiérrez, L; Araujo, B; Fuse-Moteji, R; del Castillo, E D

    1976-01-01

    The study comprised a series of 16 neonates made up of 5 patients of 33 weeks of gestation, 5 infants of 35 weeks and 6 more of 40 weeks of gestation. Blood pH, PaCO2 and HCO3- were measured together with bicarbonate, ammonium, titrable acidity and hydrogen ions in urine before and after intravenous infusion of sodium bicarbonate. Before infusion of bicarbonate, titrable acidity, ammonium and net acidity in urine were higher in accordance with a greater gestational age. As the administration of bicarbonate elapsed, titrable acidity, ammonium and net acidity dropped with increase in concentration of bicarbonate. A hypothesis is set forth that the differences found in the factors evaluated in urine before administration of bicarbonate depend on the physiologic characteristics set in the newborn by gestational age.

  15. Acupuncture suppresses intravenous methamphetamine self-administration through GABA receptor's mediation.

    Science.gov (United States)

    Choi, Yi Jeong; Kim, Nam Jun; Zhao, Rong Jie; Kim, Da Hye; Yang, Chae Ha; Kim, Hee Young; Gwak, Young S; Jang, Eun Young; Kim, Jae Su; Lee, Yun Kyu; Lee, Hyun Jong; Lee, Sang Nam; Lim, Sung Chul; Lee, Bong Hyo

    2018-01-01

    Methamphetamine is one of the widely abused drugs. In spite of a number of studies, there is still little successful therapy to suppress the methamphetamine abuse. Acupuncture has shown to attenuate the reinforcing effects of psychostimulant. Based on, the present study investigated if acupuncture could suppress intravenous methamphetamine self-administration behavior. In addition, a possible neuronal mechanism was investigated. Male Sprague-Dawley rats weighing 270-300g were trained to intake food pellet. After catheter implantation, animal was trained to self-administer methamphetamine (0.05mg/kg) intravenously using fixed ratio 1 schedule in daily 2h session during 3 weeks. After training, rats who established baseline (infusion variation less than 20% of the mean for 3 consecutive days) received acupuncture treatment on the next day. Acupuncture was performed at each acupoint manually. In the second experiment, the selective antagonists of GABA A or GABA B receptor were given before acupuncture to investigate the possible neuronal involvement of GABA receptor pathway in the acupuncture effects. C-Fos expression was examined in the nucleus accumbens to support behavioral data. Acupuncture at HT7, but not at control acupoint LI5, reduced the self-administration behavior significantly. Also, the effects of acupuncture were blocked by the GABA receptor antagonists. C-Fos expression was shown to be parallel with the behavioral data. Results of this study have shown that acupuncture at HT7 suppressed methamphetamine self-administration through GABA receptor system, suggesting that acupuncture at HT7 can be a useful therapy for the treatment of methamphetamine abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Effect of rapid intravenous administration of 50% dextrose solution on phosphorus homeostasis in postparturient dairy cows.

    Science.gov (United States)

    Grünberg, Walter; Morin, Dawn E; Drackley, James K; Constable, Peter D

    2006-01-01

    Dextrose is commonly administered to postparturient dairy cows, which often have low plasma phosphorus concentration ([P]) as a result of anorexia and sudden onset of lactation. Intravenous (IV) dextrose administration causes hypophosphatemia in other species. Bolus administration of dextrose to postparturient dairy cows results in a transient decrease in plasma [P]. Six healthy postparturient dairy cows. Using a crossover design, cows were administered 500 mL of 50% dextrose solution IV or a sham treatment. Plasma concentrations of glucose ([glucose]), immunoreactive insulin ([IRI]), and phosphorus were monitored for 12 hours after each treatment. Urine [P], [glucose], and volume and salivary [P] were also determined. Plasma [glucose], [IRI], and [P] were stable during sham treatment. Plasma [P] decreased rapidly after dextrose administration, dropping by 35% in 1 hour and remaining below baseline for 90 minutes. Salivary [P], urine [P], and urine volume per hour remained stable after dextrose administration, but glucose was detected in urine for up to 6 hours. The amount of glucose excreted in urine in 12 hours (11.9+/-4.5 g) was less than 5% of the administered dose. Regression analysis revealed a stronger association between plasma [P] and [IRI] than between plasma [P] and [glucose], suggesting that hyperinsulinemia drove the hypophosphatemia. Results indicate that low plasma [P] should be expected in cows that have received IV dextrose within 1 hour before blood sampling. Caution is advised when administering dextrose solution to cows already at risk of hypophosphatemia.

  17. Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes.

    Science.gov (United States)

    Lim, Li Ying; Koh, Pei Yin; Somani, Sukrut; Al Robaian, Majed; Karim, Reatul; Yean, Yi Lyn; Mitchell, Jennifer; Tate, Rothwelle J; Edrada-Ebel, RuAngelie; Blatchford, David R; Mullin, Margaret; Dufès, Christine

    2015-08-01

    The possibility of using gene therapy for the treatment of cancer is limited by the lack of safe, intravenously administered delivery systems able to selectively deliver therapeutic genes to tumors. In this study, we investigated if the conjugation of the polypropylenimine dendrimer to lactoferrin and lactoferricin, whose receptors are overexpressed on cancer cells, could result in a selective gene delivery to tumors and a subsequently enhanced therapeutic efficacy. The conjugation of lactoferrin and lactoferricin to the dendrimer significantly increased the gene expression in the tumor while decreasing the non-specific gene expression in the liver. Consequently, the intravenous administration of the targeted dendriplexes encoding TNFα led to the complete suppression of 60% of A431 tumors and up to 50% of B16-F10 tumors over one month. The treatment was well tolerated by the animals. These results suggest that these novel lactoferrin- and lactoferricin-bearing dendrimers are promising gene delivery systems for cancer therapy. Specific targeting of cancer cells should enhance the delivery of chemotherapeutic agents. This is especially true for gene delivery. In this article, the authors utilized a dendrimer-based system and conjugated this with lactoferrin and lactoferricin to deliver anti-tumor genes. The positive findings in animal studies should provide the basis for further clinical studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Attenuation of acute plasma cortisol response in calves following intravenous sodium salicylate administration prior to castration.

    Science.gov (United States)

    Coetzee, J F; Gehring, R; Bettenhausen, A C; Lubbers, B V; Toerber, S E; Thomson, D U; Kukanich, B; Apley, M D

    2007-08-01

    Pain associated with castration in cattle is an animal welfare concern in beef production. This study examined the effect of oral aspirin and intravenous (i.v.) sodium salicylate on acute plasma cortisol response following surgical castration. Twenty bulls, randomly assigned to the following groups, (i) uncastrated, untreated controls, (ii) castrated, untreated controls, (iii) 50 mg/kg sodium salicylate i.v. precastration and (iv) 50 mg/kg aspirin (acetylsalicylic acid) per os precastration, were blood sampled at 3, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 4, 6, 8, 10 and 12 h postcastration. Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. Data were analyzed using noncompartmental analysis, a simple cosine model, anova and t-tests. Intravenous salicylate V(d(ss)) was 0.18 L/kg, Cl(B) was 3.36 mL/min/kg and t(1/2 lambda) was 0.63 h. Plasma salicylate concentrations above 25 microg/mL coincided with significant attenuation in peak cortisol concentrations (P = 0.029). Peak salicylate concentrations following oral aspirin administration was castrated groups was significantly higher than uncastrated controls (P = 0.018). These findings have implications for designing drug regimens to provide analgesia during routine animal husbandry procedures.

  19. Corneal pharmacokinetics of the 2% diacerein eye drops between multiple administration and single administration

    OpenAIRE

    Ke Yang; Shi-Wei Chen; Xin-Yan Dou; Zhi-Rui Zhang; Xin Jin; Hong-Min Zhang

    2018-01-01

    AIM: To compare the pharmacokinetic differences of the 2% diacerein eye drops between conjunctival sac multiple administration and single administration in the cornea, and to provide the experimental basis for clinicians to use the conjunctival sac multiple administration.METHODS: Male Kunming mice were randomly divided into the multiple administration group and the single administration group. The multiple administration group were given diacerein eye drop every 2min(3 times in total). The c...

  20. Disposition kinetics of long acting moxifloxacin following intravenous administration in Sheep

    Directory of Open Access Journals (Sweden)

    Chirag M. Modi

    Full Text Available Aim: The objective of the present study was to study the disposition kinetics and dosage regimens of long acting moxifloxacin following intravenous administration at the dose rate of 7.5 mg/kg-1 b. wt. in six male sheep and to calculate dosage regimens of the same in sheep. Materials and Methods: The study was conducted using six healthy male sheep. Long acting Moxifloxacin solution (10 % moxifloxacin in solution with L- arginine, N-butyl alcohol and benzyl alcohol was injected in jugular vein and periodical blood samples were collected from contra-lateral jugular vein in test tubes containing 30-50 IU heparin (anticoagulant at 0.083 (5 min, 0.166 (10 min, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 60, 72 and up to 96 h post administration of drug. Drug concentration in plasma was determined using High Performance Liquid Chromatography (HPLC with Fluorescence Detector. The blood concentrations versus time data were analyzed using software. Results: After single dose intravenous administration of long acting moxifloxacin the plasma concentration of 0.016 ± 0.001 μg/ml-1 was maintained for up to 72 h. Distribution half-life (t and elimination half-life (t were 1.637 ± 0.053 h, and 1/2 1/2 12.130 ± 0.202 h, following IV administration. The mean values of apparent volume of distribution V 5.436 ± 0.135 L/kg-1 d(area as well as mean residence time 10.02 ± 4.787 minute were detected with IV administration. Conclusion: The long acting Moxifloxacin @ the dose 7.5 mg/kg IV maintains the effective therapeutic concentration in the plasma of sheep for up to 72 hours. The long acting Moxifloxacin at this dose rate can be used to treat sensitive bacteria causing infectious diseases in sheep. [Vet World 2012; 5(9.000: 517-521

  1. Pharmacokinetic behaviour of phenylglyoxal bis(guanylhydrazone) (PGBG) after intravenous administration in rabbits.

    Science.gov (United States)

    Rodríguez, C; San Andrés, M I; San Andrés, M D; Encinas, T; González, F; Ballesteros, E

    2001-04-01

    Phenylglyoxal bis(guanylhydrazone) (PGBG) is a synthesized analogue of methylglyoxal bis(guanylhydrazone) (MGBG), which has demonstrated anti-parasitic activity in rabbits. The pharmacokinetic behaviour of PGBG after intravenous administration (10 mg/kg bodyweight) was studied in five rabbits. Plasma concentrations of PGBG were measured by high-performance liquid chromatography. Plasma PGBG concentrations decreased rapidly and were not detectable beyond 90 min after treatment. The mean [+/- standard deviation (SD)] volume of distribution at steady state (Vdss) was 2.19 +/- 0.47 l/kg and the mean plasma clearance value (Cl) was 29.99 +/- 3.98 ml/min kg. This drug is rapidly eliminated from the body in rabbits, having a short elimination half-life (0.93 h) and mean residence time (1.21 h).

  2. Phlebitis as a consequence of peripheral intravenous administration of cisatracurium besylate in critically ill patients.

    Science.gov (United States)

    Meeder, Annelijn M; van der Steen, Marijke S; Rozendaal, Annemieke; van Zanten, Arthur R H

    2016-10-03

    This case report series describes 3 cases of cisatracurium besylate associated phlebitis after an infusion period of 14-20 hours. No similar cases have been reported in the literature. Association of phlebitis with another neuromuscular blocking agent, atracurium, has been described in the literature. The acidity of atracurium is thought to be the main cause. It is recommended that atracurium is administered only via central venous catheters when indicated to infuse over prolonged periods of time due to the acidity. Cisatracurium is a stereoisomer of atracurium and as such has the same molecular weight. Although cisatracurium also has a similar acidity as atracurium, a recommendation concerning infusion via a central venous catheter is lacking. We suggest prolonged administration of cisatracurium besylate only via centrally placed venous catheters or if not possible to careful monitor relevant peripheral intravenous sites to diminish the risks of phlebitis and associated complications or other cutaneous reactions. 2016 BMJ Publishing Group Ltd.

  3. INTRAVENOUS IMMUNOGLOBULIN ADMINISTRATION FOR DESENSITIZATION BEFORE RENAL TRANSPLANTATION AND MANAGING ANTIBODY-MEDIATED REJECTION

    Directory of Open Access Journals (Sweden)

    A. I. Sushkov

    2011-01-01

    Full Text Available Much attention has been placed recently in transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful renal transplantation, several approaches have been developed. Intravenous immunoglobulin (IVIG was found to be effective in the treatment of autoimmune and inflammatory disorders (e. g. Kawasaki disease, Guillain-Barre syndrome. Recently, a beneficial effect of IVIG on the reduc- tion of anti-HLA antibodies was described. The anti-inflammatory effect of IVIG provides hopeful opportunities in antibody-mediated rejection (AMR management. There are several protocols of IVIG administration for pre-transplant desensitization and AMR treatment: high-dose IVIG, low-dose IVIG + plasmapheresis, IVIG + plasmapheresis + rituximab. These advancements have enabled transplantation in patients previously considered untransplantable and in concert with new diagnostic techniques has resulted in new approaches to management of AMR. 

  4. Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.

    Science.gov (United States)

    Zeng, Xiao-yan; Dong, Shu; He, Nan-nan; Jiang, Chun-jie; Dai, Yue; Xia, Yu-feng

    2015-09-01

    Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Breath 14CO2 after intravenous administration of [14C]aminopyrine in liver diseases

    International Nuclear Information System (INIS)

    Pauwels, S.; Geubel, A.P.; Dive, C.; Beckers, C.

    1982-01-01

    The determination of of 14 CO2 in breath after oral administration of [ 14 C]aminopyrine has been proposed as a quantitative liver function test. In order to shorten the procedure and avoid misinterpretations related to variable rates of intestinal absorption, the [ 14 C]aminopyrine breath test (ABT) was performed after intravenous administration of [ 14 C]aminopyrine in 21 controls and 89 patients with biopsy-proven liver disease. The specific activity of the first hour sample corrected for body weight (SA1) was the most discriminant expression of breath data. The SA1 value, expressed as the percentage of the administered dose, was 0.86 +/- 0.1% (mean +/- SD) in controls and significantly less in patients (0.46 +/- 0.31%). Low values were observed in patients with untreated chronic active hepatitis (0.16 +/- 0.13%), alcoholic cirrhosis (0.2 +/ 0.15%0, and untreated postnecrotic cirrhosis (0.47 +/- 0.17%). In contrast, normal values were obtained in chronic persistent hepatitis (0.86 +/- 0.13%) and 58% of noncirrhotic alcoholic liver diseases (0.83 +/- 0.27%). The results of duplicate studies were reproducible and SA1 correlated with other conventional liver function tests, including 45-min BSP retention. Among these, ABT was the most sensitive screening test for the presence of cirrhosis, especially in alcoholic patients, where it allowed a sharp distinction between cirrhotic and noncirrhotic cases. The results obtained in chronic hepatitis suggested that ABT may provide a reliable index of the activity of the disease. In our hands, intravenous ABT, performed over a 1-hr period, was a fast, sensitive, and discriminant liver function test

  6. Pharmacokinetics of meropenem after intravenous, intramuscular and subcutaneous administration to cats.

    Science.gov (United States)

    Albarellos, Gabriela A; Montoya, Laura; Passini, Sabrina M; Lupi, Martín P; Lorenzini, Paula M; Landoni, María F

    2016-12-01

    The aim of the study was to describe the pharmacokinetics and predicted efficacy of meropenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to cats at a single dose of 10 mg/kg. Five adult healthy cats were used. Blood samples were withdrawn at predetermined times over a 12 h period. Meropenem concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed with computer software. Initial estimates were determined using the residual method and refitted by non-linear regression. The time that plasma concentrations were greater than the minimum inhibitory concentration (T >MIC) was estimated by applying bibliographic MIC values and meropenem MIC breakpoint. Maximum plasma concentrations of meropenem were 101.02 µg/ml (C p(0) , IV), 27.21 µg/ml (C max , IM) and 15.57 µg/ml (C max , SC). Bioavailability was 99.69% (IM) and 96.52 % (SC). Elimination half-lives for the IV, IM and SC administration were 1.35, 2.10 and 2.26 h, respectively. Meropenem, when administered to cats at a dose of 10 mg/kg q12h,, is effective against bacteria with MIC values of 6 μg/ml, 7 μg/ml and 10 μg/ml for IV, IM and SC administration, respectively. However, clinical trials are necessary to confirm clinical efficacy of the proposed dosage regimen. © The Author(s) 2015.

  7. Adverse Effects with Ambulatory Intravenous Immunoglobulin Administration in Adult Patients with Common Variable Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Karen Alicia Rodríguez-Mireles

    2014-06-01

    Full Text Available Background: Common variable immunode ciency (CVID is the most frequent symptomatic primary immunodeficiency, affecting 1:25,000- 75,000 people. It is characterized by the absence or decrease antibody production. Treatment for CVID consists on human immunoglobulin administration, and the intravenous route is the most common route for administration, at 400-800 mg/kg of weight every 3-4 weeks. Adverse effects associated with intravenous immunoglobulin (IVIg use occur in 25% of all infusions, with severe adverse reactions presenting in less than 1% of all patients. Acute renal failure can occur as a severe adverse reaction, which presents 1-10 days after starting IVIg treatment. In our center we implemented an ambulatory scheme for IVIg administration, which allows its administration in an average of 3 hours, without severe adverse effects. Objectives: To describe adverse effects and to evaluate the frequency of renal failure secondary to ambulatory IVIg administration in patients with common variable immunode ciency. Material and method: A descriptive and prospective study was done including adult patients con de nitive diagnosis of common variable immunodeficiency, receiving IVIg at replacement dose every 3 weeks. All patients were evaluated with clinical exploration, somatometry, serum creatinine, albumin and urea determination, 24 hours creatinine clearance, glomerular ltration rate with CKD-EPI, and immediate renal function associated with accumulated IVIg. Results were analyzed with descriptive statistics. Results: We determined adverse effects in 25 patients with common variable immunode ciency (15 women and 10 men, average age 36.7 years, during a 10 months period (January-September 2013. During this period 284 IVIg infusions were administered using our scheme, frequency of adverse effects were 12.9%, with 5.2% of early adverse effects and 7.7% late adverse effects, all being mild to moderate, in some cases required analgesic and

  8. Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

    Science.gov (United States)

    Subramaniam, B; Claudius, J S

    1990-03-08

    Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

  9. Distribution and pharmacokinetics of radiolabeled monoclonal antibody OC 125 after intravenous and intraperitoneal administration in gynecologic tumors

    International Nuclear Information System (INIS)

    Haisma, H.J.; Moseley, K.R.; Battaile, A.; Griffiths, T.C.; Knapp, R.C.

    1988-01-01

    Radiolabeled monoclonal antibodies may be useful for radioimmunotherapy of gynecologic tumors. Iodine 131-labeled F(ab')2 fragments of a monoclonal antibody, OC 125, with specificity for ovarian carcinoma, were used to study the distribution and pharmacokinetics of this antibody in patients with gynecologic tumors. The radiolabeled antibody was injected intravenously or intraperitoneally into 10 patients suspected of having ovarian cancer. Blood and urine samples were used for pharmacokinetic studies, and biopsy specimens were examined for the uptake of antibody. The serum half-life of the labeled antibody was 30 hours after intravenous administration, with 20% of the injected dose per liter detected at 24 hours. After intraperitoneal injection, the appearance of antibody in serum was slow, with a maximum level of 1.4% of the injected dose per liter at 24 hours. Urinary excretion of the radiolabeled antibody was similar for intravenous and intraperitoneal administration, with approximately 50% of the injected dose excreted after 48 hours. Intraperitoneal administration of the radiolabeled antibody resulted in a higher uptake of antibody in the tumor and a lower uptake of antibody in normal tissues. On the basis of this limited study, intraperitoneal administration of radiolabeled antibody is preferred over intravenous administration for radioimmunotherapy of ovarian cancer

  10. Effects of Arsenic Trioxide on Radiofrequency Ablation of VX2 Liver Tumor: Intraarterial versus Intravenous Administration

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Nak Jong; Yoon, Chang Jin; Kang, Sung Gwon [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Chung, Jin Wook; Kim, Hyo Cheol; Park, Jae Hyung [Seoul National University Hospital, Seoul (Korea, Republic of)

    2012-03-15

    Arsenic trioxide (As{sub 2}O{sub 3}) can be used as a possible pharmaceutical alternative that augments radiofrequency (RF) ablation by reducing tumor blood flow. The aim of this study was to assess the effect of intraarterial and intravenous administration of As{sub 2}O{sub 3} on RF-induced ablation in an experimentally induced liver tumor. VX2 carcinoma was grown in the livers of 30 rabbits. As{sub 2}O{sub 3} (1 mg/kg) was administered through the hepatic artery (n = 10, group A) or ear vein (n = 10, group B), 30 minutes before RF ablation (125 mA {+-} 35; 90 {+-} 5 degrees Celsius). As a control group, 10 rabbits were treated with RF ablation alone (group C). RF was intentionally applied to the peripheral margin of the tumor so that ablation can cover the tumor and adjacent hepatic parenchyma. Ablation areas of the tumor and adjacent parenchymal changes among three groups were compared by the Kruskal-Wallis and Mann-Whitney U test. The overall ablation areas were 156 {+-} 28.9 mm{sup 2} (group A), 119 {+-} 31.7 (group B), and 92 {+-} 17.4 (group C, p < 0.04). The ablation area of the tumor was significantly larger in group A (73 {+-} 19.7 mm{sup 2}) than both group B (50 {+-} 19.4, p = 0.02) and group C (28 {+-} 2.2, p < 0.01). The ratios of the tumoral ablation area to the overall ablation area were larger in group A (47 {+-} 10.5%) than that of the other groups (42 {+-} 7.3% in group B and 32 {+-} 5.6% in group C) (p < 0.03). Radiofrequency-induced ablation area can be increased with intraarterial or intravenous administration of As{sub 2}O{sub 3}. The intraarterial administration of As{sub 2}O{sub 3} seems to be helpful for the selective ablation of the tumor.

  11. Comparative pharmacokinetics of cefuroxime lysine after single intravenous, intraperitoneal, and intramuscular administration to rats.

    Science.gov (United States)

    Zhao, Long-shan; Yin, Ran; Wei, Bin-bin; Li, Qing; Jiang, Zhen-yuan; Chen, Xiao-hui; Bi, Kai-shun

    2012-11-01

    To compare the pharmacokinetic parameters of cefuroxime lysine, a new second-generation of cephalosporin antibiotics, after intravenous (IV), intraperitoneal (IP), or intramuscular (IM) administration. Twelve male and 12 virgin female Sprague-Dawley rats, weighing from 200 to 250 g, were divided into three groups (n=4 for each gender in each group). The rats were administered a single dose (67.5 mg/kg) of cefuroxime lysine via IV bolus or IP or IM injection. Blood samples were collected and analyzed with a validated UFLC-MS/MS method. The concentration-time data were then calculated by compartmental and non-compartmental pharmacokinetic methods using DAS software. After IV, IP or IM administration, the plasma cefuroxime lysine disposition was best described by a tri-compartmental, bi-compartmental or mono-compartmental open model, respectively, with first-order elimination. The plasma concentration profiles were similar through the 3 administration routes. The distribution process was rapid after IV administration [t(1/2(d)), 0.10 ± 0.11 h vs 1.36 ± 0.65 and 1.25 ± 1.01 h]. The AUMC(0-∞) is markedly larger, and mean residence time (MRT) is greatly longer after IP administration than that in IV, or IM routes (AUMC(0-∞): 55.33 ± 20.34 vs 16.84 ± 4.85 and 36.17 ± 13.24 mg·h(2)/L; MRT: 0.93 ± 0.10 h vs 0.37 ± 0.07 h and 0.65 ± 0.05 h). The C(max) after IM injection was significantly higher than that in IP injection (73.51 ± 12.46 vs 49.09 ± 7.06 mg/L). The AUC(0-∞) in male rats were significantly higher than that in female rats after IM administration (66.38 ± 16.5 vs 44.23 ± 6.37 mg·h/L). There was no significantly sex-related difference in other pharmacokinetic parameters of cefuroxime lysine between male and female rats. Cefuroxime lysine shows quick absorption after IV injection, a long retension after IP injection, and a high C(max) after IM injection. After IM administration the AUC(0-∞) in male rats was significantly larger than that in

  12. Pharmacokinetics of imipenem after intravenous, intramuscular and subcutaneous administration to cats.

    Science.gov (United States)

    Albarellos, Gabriela A; Denamiel, Graciela A; Montoya, Laura; Quaine, Pamela C; Lupi, Martín P; Landoni, María F

    2013-06-01

    The study describes the pharmacokinetics and predicted efficacy of imipenem after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration to five adult cats at a dose of 5 mg/kg. Susceptibility to imipenem [minimum inhibitory concentration (MIC)] was determined for antimicrobial resistant Escherichia coli (n = 13) and staphylococci (n = 3) isolated from domestic cat infections (urinary system, skin and conjunctiva). Maximum plasma concentrations of imipenem were 13.45 µg/ml (IV), 6.47 µg/ml (IM) and 3.83 µg/ml (SC). Bioavailability was 93.18% (IM) and 107.90% (SC). Elimination half-lives for IV, IM and SC administration were 1.17, 1.44 and 1.55 h, respectively. All tested bacteria were susceptible to imipenem; MIC values were 0.03 µg/ml for Staphylococcus species and imipenem concentrations remained above a MIC of 0.5 µg/ml for approximately 4 h (IV and IM) and 9 h (SC). Imipenem would be predicted to be effective for the treatment of antimicrobial resistant bacterial infections in cats at a dosage of 5 mg/kg every 6-8 h (IV, IM), or longer for the SC route. However, clinical trials are mandatory to establish its efficacy and proper dosing.

  13. Toxicological evaluation of long-term intravenous administration of amitraz in horses

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    Queiroz-Neto A.

    2002-01-01

    Full Text Available With the aim of determining the possible toxicity of amitraz after its prolonged use in horses, six English Thoroughbred horses received intravenous injections of amitraz (0.05, 0.10 or 0.15 mg/kg weekly for four months, constituting the experimental group. Eight other animals (control group, via the same route following the same drug administration schedule and period of time, received the vehicle, dimethylformamide. At the end of this period, blood was collected from all the animals, and a comparison was made of the means of the values obtained for the various blood analyses: complete hemogram, alkaline phosphatase, gamma-glutamyltransferase, blood urea nitrogen, lactate dehydrogenase, aspartate aminotransferase, creatine phosphokinase, glucose, albumin, total protein, creatinine, Na+ , K+, Cl- and CO2. The results for the biochemical characteristics showed that only the mean value for urea of the animals submitted to treatment with amitraz was significantly different than the mean value obtained for the control group. The analyses of the hematological characteristics showed that no significant differences between groups were observed. Similarly, the measurement of blood electrolyte levels demonstrated that long-term treatment with amitraz did not cause significant changes in the variables analyzed. The results indicate that amitraz, given in the doses employed in this study, did not show signs of inducing toxic effects in vital organs, even after prolonged administration.

  14. Effects of Arsenic Trioxide on Radiofrequency Ablation of VX2 Liver Tumor: Intraarterial versus Intravenous Administration

    International Nuclear Information System (INIS)

    Seong, Nak Jong; Yoon, Chang Jin; Kang, Sung Gwon; Chung, Jin Wook; Kim, Hyo Cheol; Park, Jae Hyung

    2012-01-01

    Arsenic trioxide (As 2 O 3 ) can be used as a possible pharmaceutical alternative that augments radiofrequency (RF) ablation by reducing tumor blood flow. The aim of this study was to assess the effect of intraarterial and intravenous administration of As 2 O 3 on RF-induced ablation in an experimentally induced liver tumor. VX2 carcinoma was grown in the livers of 30 rabbits. As 2 O 3 (1 mg/kg) was administered through the hepatic artery (n = 10, group A) or ear vein (n = 10, group B), 30 minutes before RF ablation (125 mA ± 35; 90 ± 5 degrees Celsius). As a control group, 10 rabbits were treated with RF ablation alone (group C). RF was intentionally applied to the peripheral margin of the tumor so that ablation can cover the tumor and adjacent hepatic parenchyma. Ablation areas of the tumor and adjacent parenchymal changes among three groups were compared by the Kruskal-Wallis and Mann-Whitney U test. The overall ablation areas were 156 ± 28.9 mm 2 (group A), 119 ± 31.7 (group B), and 92 ± 17.4 (group C, p 2 ) than both group B (50 ± 19.4, p = 0.02) and group C (28 ± 2.2, p 2 O 3 . The intraarterial administration of As 2 O 3 seems to be helpful for the selective ablation of the tumor.

  15. Protein Adsorption to In-Line Filters of Intravenous Administration Sets.

    Science.gov (United States)

    Besheer, Ahmed

    2017-10-01

    Ensuring compatibility of administered therapeutic proteins with intravenous administration sets is an important regulatory requirement. A low-dose recovery during administration of low protein concentrations is among the commonly observed incompatibilities, and it is mainly due to adsorption to in-line filters. To better understand this phenomenon, we studied the adsorption of 4 different therapeutic proteins (2 IgG1s, 1 IgG4, and 1 Fc fusion protein) diluted to 0.01 mg/mL in 5% glucose (B. Braun EcoFlac; B. Braun Melsungen AG, Melsungen, Germany) or 0.9% sodium chloride (NaCl; Freeflex; Fresenius Kabi, Friedberg, Germany) solutions to 8 in-line filters (5 positively charged and 3 neutral filters made of different polymers and by different suppliers). The results show certain patterns of protein adsorption, which depend to a large extent on the dilution solution and filter material, and to a much lower extent on the proteins' biophysical properties. Investigation of the filter membranes' zeta potential showed a correlation between the observed adsorption pattern in 5% glucose solution and the filter's surface charge, with higher protein adsorption for the strongly negatively charged membranes. In 0.9% NaCl solution, the surface charges are masked, leading to different adsorption patterns. These results contribute to the general understanding of the protein adsorption to IV infusion filters and allow the design of more efficient compatibility studies. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  16. 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.

  17. Pharmacokinetics after intravenous, subcutaneous, and oral administration of enrofloxacin to alpacas.

    Science.gov (United States)

    Gandolf, A Rae; Papich, Mark G; Bringardner, Amy B; Atkinson, Mark W

    2005-05-01

    To determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after p.o, s.c., and i.v. administration of enrofloxacin to alpacas. 6 adult female alpacas. A crossover design was used for administration of 3 single-dose treatments of enrofloxacin to alpacas, which was followed by an observational 14-day multiple-dose regimen. Single-dose treatments consisted of i.v. and s.c. administration of injectable enrofloxacin (5 mg/kg) and p.o administration of enrofloxacin tablets (10 mg/kg) dissolved in grain to form a slurry. Plasma enrofloxacin concentrations were measured by use of high-performance liquid chromatography. The multiple-dose regimen consisted of feeding a mixture of crushed and moistened enrofloxacin tablets mixed with grain. Behavior, appetite, and fecal quality were monitored throughout the 14-day treatment regimen and for 71 additional days following treatment. Mean half-life following i.v., s.c., and p.o. administration was 11.2, 8.7, and 16.1 hours, respectively. For s.c. and p.o administration, mean total systemic availability was 90.18% and 29.31%, respectively; mean maximum plasma concentration was 3.79 and 1.81 microg/mL, respectively; and area under the curve (AUC) was 50.05 and 33.97 (microg x h)/mL, respectively. The s.c. or p.o administration of a single dose of enrofloxacin yielded a ratio for AUC to minimum inhibitory concentration > 100 for many grampositive and gram-negative bacterial pathogens common to camelids. Conclusions and Clinical Relevance-The administration of enrofloxacin (5 mg/kg, s.c., or 10 mg/kg, p.o) may be appropriate for antimicrobial treatment of alpacas.

  18. Pharmacokinetics of butorphanol after intravenous, intramuscular, and oral administration in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Guzman, David Sanchez-Migallon; Flammer, Keven; Paul-Murphy, Joanne R; Barker, Steven A; Tully, Thomas N

    2011-09-01

    Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (Amazon

  19. Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

    Directory of Open Access Journals (Sweden)

    Mohamed Aboubakr

    2014-01-01

    Full Text Available The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV and oral (PO dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t1/2(β and mean residence time (MRT were longer in renal damaged ducks than in healthy ones. Total clearance (Cltot in renal damaged ducks (0.20 L kg−1 h−1 was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1. Following PO administration, the peak serum concentration (Cmax was higher in renal damaged than in healthy ducks and was achieved at maximum time (tmax of 2.47 and 2.05 h, respectively. The drug was eliminated (t1/2(el at a significant slower rate (3.94 h in renal damaged than in healthy ducks (2.89 h. The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values for Cmax/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.

  20. Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route.

    Science.gov (United States)

    Hokkanen, Ann-Helena; Raekallio, Marja R; Salla, Kati; Hänninen, Laura; Viitasaari, Elina; Norring, Marianna; Raussi, Satu; Rinne, Valtteri M; Scheinin, Mika; Vainio, Outi M

    2014-07-01

    To study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously (IV) administered detomidine. Randomised, prospective clinical study. Twenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg. Detomidine at 80 μg kg(-1) was administered to ten calves sublingually (GEL) and at 30 μg kg(-1) to ten control calves IV (V. jugularis). Meloxicam (0.5 mg kg(-1) ) and local anaesthetic (lidocaine 3 mg kg(-1) ) were administered before heat cauterization of horn buds. Heart rate (HR), body temperature and clinical sedation were monitored over 240 minutes. Blood was collected from the V. cephalica during the same period for drug concentration analysis. Pharmacokinetic variables were calculated from the plasma detomidine concentration-time data using non-compartmental methods. Statistical analyses compared routes of administration by Student's t-test and linear mixed models as relevant. The maximum plasma detomidine concentration after GEL was 2.1 ± 1.2 ng mL(-1) (mean ±SD) and the time of maximum concentration was 66.0 ± 36.9 minutes. The bioavailability of detomidine was approximately 34% with GEL. Similar sedation scores were reached in both groups after administration of detomidine, but maximal sedation was reached earlier in the IV group (10 minutes) than in the GEL group (40 minutes). HR was lower after IV than GEL from 5 to 10 minutes after administration. All animals were adequately sedated, and we were able to administer local anaesthetic without resistance to all of the calves before disbudding. Oromucosally administered detomidine is an effective sedative agent for calves prior to disbudding. © 2014 The Authors Veterinary Anaesthesia and Analgesia published by John Wiley & Sons Ltd on behalf of Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  1. Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after intravenous and oral administration.

    Science.gov (United States)

    Gharibi, S; Kimble, B; Vogelnest, L; Barnes, J; Stadler, C K; Govendir, M

    2017-12-01

    The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, respectively. Plasma concentrations of posaconazole were quantified by validated high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady-state volume of distribution (V ss ) were 0.15 (0.13-0.18) L hr -1  kg -1 and 1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life (t 1/2 ) after i.v. and p.o. administration was 7.90 (7.62-8.18) and 12.79 (11.22-16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (C max ; median: 0.72, range: 0.55-0.93 μg/ml) was achieved in 8 (range 6-12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25 ± 0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas. © 2017 John Wiley & Sons Ltd.

  2. Combination Intravenous and Intra-Articular Tranexamic acid compared with Intravenous Only Administration and No Therapy in Total Knee Arthroplasty: A Case Series Study

    Directory of Open Access Journals (Sweden)

    Chris Buntting

    2016-07-01

    This study supports the existing literature and suggests that the use of IV Tranexamic acid alone or in combination with intra-articular dose in TKA may reduce the requirement for transfusion (Level IV evidence. Furthermore, this study suggests that the use of tranexamic acid as a combination of Intravenous and intra-articular administration has no effect on range of motion, or medical complications during hospital stay. Although it was not a statistically significant finding, our study suggested a trend towards a greater reduction in haemoglobin and haematocrit fall in the combination therapy group when compared to IV Tranexamic acid alone

  3. Effect of Intravenous Administration of Contrast Media on Serum Creatinine Levels in Neonates.

    Science.gov (United States)

    Bedoya, Maria A; White, Ammie M; Edgar, J Christopher; Pradhan, Madhura; Raab, Elisabeth L; Meyer, James S

    2017-08-01

    Purpose To assess the effect of intravenous contrast media on renal function in neonates. Materials and Methods Institutional review board approval was obtained with waiver of consent. Electronic health records from January 2011 to April 2013 were reviewed retrospectively. Measures of renal function were obtained in inpatient neonates who underwent magnetic resonance (MR) imaging or computed tomography (CT) and for whom serum creatinine (Cr) levels were obtained within 72 hours before imaging and at least one time after imaging (>1 day after administration of contrast material). A total of 140 neonates who received contrast material (59 who underwent CT with iohexol or iodixanol and 81 who underwent MR imaging with gadopentetate dimeglumine) were identified. These neonates were frequency matched according to sex, gestational and postnatal age, and preimaging serum Cr levels with neonates who underwent unenhanced MR imaging or CT. Cr levels and glomerular filtration rates (GFRs) were grouped according to when they were obtained (before imaging, 1-2 days after imaging, 3-5 days after imaging, 6-9 days after imaging, 10-45 days after imaging, and more than 45 days after imaging). Serum Cr levels and GFRs for each time period were compared between groups by using hierarchic regressions or χ 2 or Fisher exact tests and with repeated-measures analysis of variance to compare groups on the rate of change in serum Cr levels and GFRs from before to after imaging. Results Cr levels decreased and GFRs increased in both groups from before to after imaging (CT group, P ≤ .01; MR imaging group, P ≤ .01). The neonates who underwent contrast material-enhanced imaging and the neonates who underwent unenhanced imaging showed similar serum Cr levels at all examined time periods. Groups also did not differ in the proportion of neonates with serum Cr levels higher than the reference range (>0.4 mg/dL) at any time point (iodine- [P > .12] or gadolinium-based [P > .13] contrast

  4. Quality of abdominal computed tomography angiography: hand versus mechanical intravenous contrast administration in children

    Energy Technology Data Exchange (ETDEWEB)

    Ayyala, Rama S.; Lee, Edward Y. [Boston Children' s Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Zurakowski, David [Boston Children' s Hospital and Harvard Medical School, Departments of Anesthesiology and Surgery, Boston, MA (United States)

    2015-11-15

    Abdominal CT angiography has been increasingly used for evaluation of various conditions related to abdominal vasculature in the pediatric population. However, no direct comparison has evaluated the quality of abdominal CT angiography in children using hand versus mechanical administration of intravenous (IV) contrast agent. To compare hand versus mechanical administration of IV contrast agent in the quality of abdominal CT angiography in the pediatric population. We retrospectively reviewed the electronic medical record to identify pediatric patients (≤18 years) who had abdominal CT angiography between August 2012 and August 2013. The information obtained includes: (1) type of administration of IV contrast agent (hand [group 1] versus mechanical [group 2]), (2) size (gauge) of IV catheter, (3) amount of contrast agent administered and (4) rate of contrast agent administration (ml/s). Two reviewers independently performed qualitative and quantitative evaluation of abdominal CT angiography image quality. Qualitative evaluation of abdominal CT angiography image quality was performed by visual assessment of the degree of contrast enhancement in the region of interest (ROI) based on a 4-point scale. Quantitative evaluation of each CT angiography examination was performed by measuring the Hounsfield unit (HU) using an ROI within the abdominal aorta at two levels (celiac axis and the inferior mesenteric artery) for each child. Analysis of variance (ANOVA) using the F-test was applied to compare contrast enhancement within the abdominal aorta at two levels (celiac axis and inferior mesenteric artery) between hand administration and mechanical administration of IV contrast methods with adjustment for age. We identified 46 pediatric patients (24 male, 22 female; mean age 7.3 ± 5.5 years; range 5 weeks to 18 years) with abdominal CT angiography performed during the study period. Of these patients, 16 (35%; 1.7 ± 2.2 years; range 5 weeks to 5 years) had hand

  5. Quality of abdominal computed tomography angiography: hand versus mechanical intravenous contrast administration in children

    International Nuclear Information System (INIS)

    Ayyala, Rama S.; Lee, Edward Y.; Zurakowski, David

    2015-01-01

    Abdominal CT angiography has been increasingly used for evaluation of various conditions related to abdominal vasculature in the pediatric population. However, no direct comparison has evaluated the quality of abdominal CT angiography in children using hand versus mechanical administration of intravenous (IV) contrast agent. To compare hand versus mechanical administration of IV contrast agent in the quality of abdominal CT angiography in the pediatric population. We retrospectively reviewed the electronic medical record to identify pediatric patients (≤18 years) who had abdominal CT angiography between August 2012 and August 2013. The information obtained includes: (1) type of administration of IV contrast agent (hand [group 1] versus mechanical [group 2]), (2) size (gauge) of IV catheter, (3) amount of contrast agent administered and (4) rate of contrast agent administration (ml/s). Two reviewers independently performed qualitative and quantitative evaluation of abdominal CT angiography image quality. Qualitative evaluation of abdominal CT angiography image quality was performed by visual assessment of the degree of contrast enhancement in the region of interest (ROI) based on a 4-point scale. Quantitative evaluation of each CT angiography examination was performed by measuring the Hounsfield unit (HU) using an ROI within the abdominal aorta at two levels (celiac axis and the inferior mesenteric artery) for each child. Analysis of variance (ANOVA) using the F-test was applied to compare contrast enhancement within the abdominal aorta at two levels (celiac axis and inferior mesenteric artery) between hand administration and mechanical administration of IV contrast methods with adjustment for age. We identified 46 pediatric patients (24 male, 22 female; mean age 7.3 ± 5.5 years; range 5 weeks to 18 years) with abdominal CT angiography performed during the study period. Of these patients, 16 (35%; 1.7 ± 2.2 years; range 5 weeks to 5 years) had hand

  6. Quality of abdominal computed tomography angiography: hand versus mechanical intravenous contrast administration in children.

    Science.gov (United States)

    Ayyala, Rama S; Zurakowski, David; Lee, Edward Y

    2015-11-01

    Abdominal CT angiography has been increasingly used for evaluation of various conditions related to abdominal vasculature in the pediatric population. However, no direct comparison has evaluated the quality of abdominal CT angiography in children using hand versus mechanical administration of intravenous (IV) contrast agent. To compare hand versus mechanical administration of IV contrast agent in the quality of abdominal CT angiography in the pediatric population. We retrospectively reviewed the electronic medical record to identify pediatric patients (≤18 years) who had abdominal CT angiography between August 2012 and August 2013. The information obtained includes: (1) type of administration of IV contrast agent (hand [group 1] versus mechanical [group 2]), (2) size (gauge) of IV catheter, (3) amount of contrast agent administered and (4) rate of contrast agent administration (ml/s). Two reviewers independently performed qualitative and quantitative evaluation of abdominal CT angiography image quality. Qualitative evaluation of abdominal CT angiography image quality was performed by visual assessment of the degree of contrast enhancement in the region of interest (ROI) based on a 4-point scale. Quantitative evaluation of each CT angiography examination was performed by measuring the Hounsfield unit (HU) using an ROI within the abdominal aorta at two levels (celiac axis and the inferior mesenteric artery) for each child. Analysis of variance (ANOVA) using the F-test was applied to compare contrast enhancement within the abdominal aorta at two levels (celiac axis and inferior mesenteric artery) between hand administration and mechanical administration of IV contrast methods with adjustment for age. We identified 46 pediatric patients (24 male, 22 female; mean age 7.3 ± 5.5 years; range 5 weeks to 18 years) with abdominal CT angiography performed during the study period. Of these patients, 16 (35%; 1.7 ± 2.2 years; range 5 weeks to 5 years) had hand

  7. Comparative pharmacokinetics of cefoperazone following intravenous and intramuscular administration in goats

    Directory of Open Access Journals (Sweden)

    Taha Attia

    2015-06-01

    Full Text Available The pharmacokinetic profile of cefoperazone was studied in goats following intravenous and intramuscular administration of 20 mg/kg body weight. Cefoperazone concentrations in serum were determined by microbiological assay technique using Escherichia coli (ATCC 10536 as test organism. Following i.v. administration, the cefoperazone serum concentration–time curve was best fitted in a two compartment open model. Cefoperazone has moderate distribution in the body of goats with Vdss of 0.44 ± 0.03 L/kg. The elimination half-life (T0.5(β, area under curve (AUC and total body clearance (Cltot were 1.97 ± 0.14 h, 149.63 ± 8.61 μg ml−1 h−1, and 2.17 ml/min/kg, respectively. Following i.m. administration, the drug was very rapidly absorbed, with an absorption half-life (T0.5(ab of 0.12 ± 0.01 h. The maximum serum concentration (Cmax of 30.42 ± 3.53 μg ml−1 was attained at (Tmax 0.58 ± 0.02 h, with an elimination half-life (T0.5(el of 2.53 ± 0.11 h. The systemic bioavailability of cefoperazone in the goats after i.m. administration was 83.62% and in vitro protein binding was 20.34%. The serum concentrations of cefoperazone along 12 h post i.m. injection in this study were exceeding the MIC of different susceptible micro-organisms responsible for serious disease problems. Consequently, a suitable intramuscular dosage regimen for cefoperazone was 20 mg/kg repeated at 12 h intervals in goats. The drug was detected in urine up to 12 and 18 h following i.v. and i.m. administration, respectively.

  8. Pharmacokinetics and selected pharmacodynamics of trazodone following intravenous and oral administration to horses undergoing fitness training.

    Science.gov (United States)

    Knych, Heather K; Mama, Khursheed R; Steffey, Eugene P; Stanley, Scott D; Kass, Philip H

    2017-10-01

    OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.

  9. Sex differences in nicotine intravenous self-administration: A meta-analytic review.

    Science.gov (United States)

    Flores, Rodolfo J; Uribe, Kevin P; Swalve, Natashia; O'Dell, Laura E

    2017-11-21

    This report reflects a meta-analysis that systematically reviewed the literature on intravenous self-administration (IVSA) of nicotine in female and male rats. The goal was to determine if sex differences in nicotine IVSA exist, estimate the magnitude of the effect, and identify potential moderators of the relationship between sex differences and nicotine consumption. Extensive search procedures identified 20 studies that met the inclusion criteria of employing both female and male rats in nicotine IVSA procedures. The meta-analysis was conducted on effect size values that were calculated from mean total intake or nicotine deliveries using the Hedges' unbiased g u statistic. A random effects analysis revealed that overall females self-administered more nicotine than males (weighted g u =0.18, 95% CI [0.003, 0.34]). Subsequent moderator variable analyses revealed that certain procedural conditions influenced the magnitude of sex differences in nicotine IVSA. Specifically, higher reinforcement requirements (>FR1) and extended-access sessions (23h) were associated with greater nicotine IVSA in females versus males. Females also displayed higher nicotine intake than males when the experiment included a light cue that signaled nicotine delivery. Sex differences were not influenced by the diurnal phase of testing, dose of nicotine, or prior operant training. Overall, the results revealed that female rats display higher levels of nicotine IVSA than males, suggesting that the strong reinforcing effects of nicotine promote tobacco use in women. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. MDCT urography: retrospective determination of optimal delay time after intravenous contrast administration

    International Nuclear Information System (INIS)

    Meindl, Thomas; Coppenrath, Eva; Kahlil, Rami; Reiser, Maximilian F.; Mueller-Lisse, U.G.; Mueller-Lisse, Ulrike L.

    2006-01-01

    The optimal delay time after intravenous (i.v.) administration of contrast medium (CM) for opacifcation of the upper urinary tract (UUT) for multidetector computed tomography urography (MDCTU) was investigated. UUT opacification was retrospectively evaluated in 36 four-row MDCTU examinations. Single- (n=10) or dual-phase (n=26) MDCTU was performed with at least 5-min delay after i.v. CM. UUT was divided into four sections: intrarenal collecting system (IRCS), proximal, middle and distal ureter. Two independent readers rated UUT opacification: 1, none; 2, partial; 3, complete. Numbers and percentages of scores, and the 5%, 25%, 50%, 75% and 95% percentiles of delay time were calculated for each UUT section. After removing diseased segments, 344 segments were analysed. IRCS, proximal and middle ureter were completely opacified in 94% (81/86), 93% (80/86) and 77% (66/86) of cases, respectively. Median delay time was 15 min for complete opacification. The distal ureter was completely opacified in 37% (32/86) of cases and not opacified in 26% (22/86). Median delay time for complete opacification was 11 min with 25% and 75% percentiles of 10 and 16 min, respectively. At MDCTU, opacification of the IRCS, proximal and middle ureter was hardly sensitive to delay time. Delay times between 10 and 16 min were favourable in the distal ureter. (orig.)

  11. Changes in Renal Function in Elderly Patients Following Intravenous Iodinated Contrast Administration: A Retrospective Study

    International Nuclear Information System (INIS)

    Alsafi, A.; Alsafi, Z.; Lakhani, A.; Strickland, N.H.

    2014-01-01

    Contrast-induced nephropathy (CIN) is a recognised complication of intravascular administration of iodinated contrast media (ICM). Previous studies suggest a higher incidence in the elderly, but no large study has assessed this to date. We set out to assess changes in creatinine in elderly inpatients following computed tomography (CT) examination and compare those who received intravenous contrast to those who did not. Methods. Using the Radiology Information System in two teaching hospitals, inpatients over the age of seventy who had a CT examination and a baseline creatinine were identified and their follow-up creatinine levels were analysed. Elderly inpatients who underwent a non contrast CT over the same period were used as controls. Results. 677 elderly inpatients who received ICM were compared with 487 controls. 9.2% of patients who received ICM developed acute kidney injury (AKI) compared to 3.5% of inpatient controls (Ρ<0.0001). Patients with higher baseline eGFR had a higher incidence of post-CT AKI. Conclusions. The incidence of post-CT AKI is higher in patients who received IV ICM compared to those who did not; the difference may be partly attributable to contrast-induced nephropathy. This suggests that the incidence of CIN in the elderly may not be as high as previously thought.

  12. The elimination rate of 123I-heptadecanoic acid after intracoronary and intravenous administration

    International Nuclear Information System (INIS)

    Visser, F.C.; Eenige, M.J. van; Wall, E.E. van der; Engelen, C.J. van; Cock, C.C. de; Roos, J.P.; Westera, G.; Lingen, A. van; Hollander, W. den; Heidendal, G.A.K.

    1985-01-01

    When calculating the elimination rate of radioactivity after the administration of radioiodinated heptadecanoic acid ( 123 I-HDA), background correction is necessary due to the high level of background activity. In the present study, the subtraction method of Freundlieb et al. was investigated by comparing the half-time values of the elimination rate after intravenous (i.v.) and intracoronary (i.c.) injection. In the latter case, no background correction was necessary. Six patients undergoing cardiac catheterization were studied. Scintigraphy was performed after the injection of 123 I-HDA into the left coronary artery and after i.v. injection. Half-time values are calculated from regions of interest drawn over myocardium perfused by the left-anterior descending branch (LAD) and the left circumflex artery (LCX). In the LAD region, the mean half-time value in the i.c. study was 22 min, while in the corrected i.v. study, the mean value was 27 min. In the LCX region, the half-time values were 24 and 33 min, respectively. The background-subtraction procedure proposed by Freundlieb et al. for i.v.-injected 123 I-HDA is incomplete, as it resulted in half-time values that were higher than those of the i.c. study. (orig.)

  13. Safe intravenous administration in pediatrics: A 5-year Pediatric Intensive Care Unit experience with smart pumps.

    Science.gov (United States)

    Manrique-Rodríguez, S; Sánchez-Galindo, A C; Fernández-Llamazares, C M; Calvo-Calvo, M M; Carrillo-Álvarez, Á; Sanjurjo-Sáez, M

    2016-10-01

    To estimate the impact of smart pump implementation in a pediatric intensive care unit in terms of number and type of administration errors intercepted. Observational, prospective study carried out from January 2010 to March 2015 with syringe and great volumen infusion pumps available in the hospital. A tertiary level hospital pediatric intensive care unit. Infusions delivered with infusion pumps in all pediatric intensive care unit patients. Design of a drug library with safety limits for all intravenous drugs prescribed. Users' compliance with drug library as well as number and type of errors prevented were analyzed. Two hundred and eighty-three errors were intercepted during 62 months of study. A high risk drug was involved in 58% of prevented errors, such as adrenergic agonists and antagonists, sedatives, analgesics, neuromuscular blockers, opioids, potassium and insulin. Users' average compliance with the safety software was 84%. Smart pumps implementation has proven effective in intercepting high risk drugs programming errors. These results might be exportable to other critical care units, involving pediatric or adult patients. Interdisciplinary colaboration is key to succeed in this process. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  14. Pharmacokinetics and pharmacodynamics of d-chlorpheniramine following intravenous and oral administration in healthy Thoroughbred horses.

    Science.gov (United States)

    Kuroda, Taisuke; Nagata, Shun-ichi; Takizawa, Yoshimasa; Tamura, Norihisa; Kusano, Kanichi; Mizobe, Fumiaki; Hariu, Kazuhisa

    2013-08-01

    The pharmacokinetics of d-chlorpheniramine (CPM), a histamine H1-receptor antagonist, and its ability to inhibit of histamine-induced cutaneous wheal formation, were studied in healthy Thoroughbred horses (n=5). Following an intravenous (IV) dose of 0.5mg/kg bodyweight (BW), plasma drug disposition was very rapid, with the mean terminal half-life and total body clearance calculated as 2.7h and 0.7 L/h/kg, respectively. The observed maximal inhibition of wheal formation following IV doses of 0.1 and 0.5mg/kg BW were 37.8% and 60.6% at 0.5h, respectively. Oral administration of CPM (0.5mg/kg BW) resulted in a bioavailability of 38%, which induced a peak plasma drug concentration at 1h and a maximal inhibition of wheal formation (39%) at 2h. A pharmacokinetic/pharmacodynamic link model showed that CPM in horses has lower efficacy, much lower potency and slightly lower sensitivity than other reported antihistamines. These results indicated that CPM should be administered at frequent intervals or at large dose rates to maintain therapeutic concentrations in horses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Pharmacokinetics and pharmacodynamic effects of amiodarone in plasma of ponies after single intravenous administration

    International Nuclear Information System (INIS)

    Trachsel, D.; Tschudi, P.; Portier, C.J.; Kuhn, M.; Thormann, W.; Scholtysik, G.; Mevissen, M.

    2004-01-01

    Atrial fibrillation is a well-known heart disease in horses. The common therapy consists of administration of quinidine. More potent antiarrhythmic drugs have become available for human therapy and the use of these as alternatives to quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone (AMD) is used in human medicine for treatment of many arrhythmias, including atrial fibrillation. Its disposition in horses has not yet been investigated. The purpose of this study was to measure the effect of single intravenous doses of amiodarone (5 and 7 mg/kg) on the surface electrocardiogram (ECG) of healthy minishetland ponies during the first 2 days after drug administration and to calculate pharmacokinetic parameters with a physiologically based pharmacokinetic model (PBPK) using amiodarone and desethylamiodarone (DAMD) plasma levels that were determined by high-performance liquid chromatography (HPLC). As expected for a K + -channel-blocker, the main effect on the measured ECG could be seen on the ventricular complex, as the QT interval and the T wave showed statistically significant alterations. The doses investigated were well tolerated clinically. Results from the pharmacokinetic model were found to compare well with literature data of rats, dogs, and humans. It showed a rapid distribution in the tissue, beginning with the rapidly perfused tissue, like the heart, followed by slowly perfused tissues, and finally an accumulation in fat. The half-life for total elimination was calculated to be 16.3 days with 99% eliminated by 97 days. The model predicts that approximately 96% of amiodarone is eliminated as desethylamiodarone in urine, 2% eliminated as desethylamiodarone in bile, and 2% as other metabolites

  16. The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection

    Directory of Open Access Journals (Sweden)

    Jin JF

    2015-07-01

    Full Text Available Jing-fen Jin,1 Ling-ling Zhu,2 Meng Chen,3 Hui-min Xu,3 Hua-fen Wang,1 Xiu-qin Feng,1 Xiu-ping Zhu,3 Quan Zhou31Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaBackground: Intravenous (IV, intramuscular (IM, and subcutaneous (SC are the three most frequently used injection routes in medication administration. Comparative studies of SC versus IV, IM versus IV, or IM versus SC have been sporadically conducted, and some new findings are completely different from the dosage recommendation as described in prescribing information. However, clinicians may still be ignorant of such new evidence-based findings when choosing treatment methods.Methods: A literature search was performed using PubMed, MEDLINE, and Web of Sciences™ Core Collection to analyze the advantages and disadvantages of SC, IV, and IM administration in head-to-head comparative studies.Results: “SC better than IV” involves trastuzumab, rituximab, antitumor necrosis factor medications, bortezomib, amifostine, recombinant human granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, recombinant interleukin-2, immunoglobulin, epoetin alfa, heparin, and opioids. “IV better than SC” involves ketamine, vitamin K1, and abatacept. With respect to insulin and ketamine, whether IV has advantages over SC is determined by specific clinical circumstances. “IM better than IV” involves epinephrine, hepatitis B immunoglobulin, pegaspargase, and some antibiotics. “IV better than IM” involves ketamine, morphine, and antivenom. “IM better than SC” involves epinephrine. “SC better than IM” involves interferon-beta-1a, methotrexate, human chorionic gonadotropin, hepatitis B immunoglobulin, hydrocortisone, and morphine. Safety, efficacy, patient preference, and pharmacoeconomics are four principles

  17. 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

  18. Cardiovascular side-effects and insulin secretion after intravenous administration of radiolabeled Exendin-4 in pigs

    International Nuclear Information System (INIS)

    Rydén, Anneli; Nyman, Görel; Nalin, Lovisa; Andreasson, Susanne; Korsgren, Olle; Eriksson, Olof; Jensen-Waern, Marianne

    2016-01-01

    Introduction: Radiolabeled Exendin-4, a synthetic glucagon-like peptide-1 (GLP-1) analog, is used as a tracer for diagnostic purposes of β-cells and in experimental animal research. Exendin-4 can be radiolabeled with 68 Ga, 111 In or 99m Tc and used for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging to diagnose insulinomas, visualization of pancreatic β-cell mass and transplanted Islets of Langerhans. In humans, Exendin-4 is widely used as a therapeutic agent for treatment of type 2 diabetes (T2D). The compound, which is administered subcutaneously (SC) may cause nausea, vomiting and a minor increase in the heart rate (HR). However, possible side-effects on cardiovascular functions after intravenous (IV) administration have not been reported. This study describes the Exendin-4 dose at which cardiovascular side-effects occur in pigs and cynomolgus monkeys. The IV effect of the tracer on insulin secretion is also investigated in pigs. Methods: Seven clinically healthy littermate pigs (40 days old) were used; three of them were made diabetic by streptozotocin (STZ). All pigs underwent PET imaging under general anesthesia to examine the glucagon-like peptide-1 receptor (GLP-1R) in β-cells with radiolabeled Exendin-4. A baseline tracer dose IV [ 68 Ga]Exendin-4 (0.025 ± 0.010 μg/kg) followed by a competition dose IV [ 68 Ga]Exendin-4 (3.98 ± 1.33 μg/kg) 60 min later were administered. Blood samples were taken and analyzed for insulin secretion by using ELISA. Cardiovascular and respiratory variables were monitored throughout the experiment. Results: Immediately after administration of the high dose [ 68 Ga]Exendin-4 the HR rose from 122 ± 14 to 227 ± 40 bpm (p < 0.01) and from 100 ± 5 to 181 ± 13 bpm (p < 0.01) in healthy non-diabetic and diabetes-induced pigs, respectively. The tachycardia was observed for > 2 h and one healthy non-diabetic pig suffered cardiac arrest 3 h after the IV [ 68 Ga]Exendin-4

  19. Topical vs. intravenous administration of tranexamic acid in knee arthroplasty and prevalence of deep venous thrombosis: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Ari Zekcer

    Full Text Available Abstract Background Tranexamic acid (TXA is widely used in orthopedic surgery to reduce perioperative bleeding. Since TXA inhibits fibrinolysis, there is concern that it may increase the risk of thromboembolic events. Objectives To verify the prevalence of deep venous thrombosis (DVT in patients receiving TXA during total knee arthroplasty and to compare topical with intravenous administration of the drug. Methods All patients admitted for total knee arthroplasty due to primary arthrosis between June and November of 2014 were recruited consecutively. Thirty patients were randomized to a “topical group” (1.5 g TXA diluted in 50ml saline sprayed over the area operated, before tourniquet release, 30 to an “intravenous group” (20mg/kg TXA in 100 ml of saline, given at the same time as anesthesia, and 30 to a control group (100 ml of saline, given at the same time as anesthesia. All patients had duplex ultrasound scans of the legs on the 15th postoperative day. Results Deep venous thrombosis events occurred in five of the 90 patients operated (one out of 30 in the topical group [3.3%], four out of 30 in the control group [13.3%], and zero in the intravenous group. All were confirmed by duplex ultrasound scans and all were asymptomatic. Prevalence rates of DVT were similar between groups (p = 0.112 for control vs. intravenous; p = 0.353 for control vs. topical; and p =1.000 for intravenous vs. topical, according to two-sided exact tests. Conclusions Both topical and intravenous administration of TXA are safe with regard to occurrence of DVT, since the number of DVT cases in patients given TXA was not different to the number in those given placebo.

  20. Intravenous saline administration in patients with severe acquired brain injury and orthostatic intolerance for tilt-table mobilization

    DEFF Research Database (Denmark)

    Riberholt, Christian; Olesen, Niels; Hovind, Peter

    2018-01-01

    Primary objective: This study aimed to investigate the effect of intravenous saline administration on orthostatic hypotension (OH) during head up tilt (HUT) and the change in the renin–angiotensin–aldosterone system before and after HUT in patients with severe acquired brain injury (ABI). Research...... artery blood flow velocity. Blood samples were collected before and after two HUT sessions separated by 1 hour and saline was administered in between. Main outcomes and results: Patients’ ability to stand upright did not change after saline administration due to OH. The patients showed signs of reduced...... fluid administration. Research focusing on the ability to retain fluid after bed rest is warranted....

  1. Oral versus intravenous methylprednisolone for the treatment of multiple sclerosis relapses: A meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Shuo Liu

    Full Text Available Intravenous glucocorticoids are recommended for multiple sclerosis (MS. However, they can be inconvenient and expensive. Due to their convenience and low cost, oral glucocorticoids may be an alternative treatment. Recently, several studies have shown that there is no difference in efficacy and safety between oral methylprednisolone (oMP and intravenous methylprednisolone (ivMP.We sought to assess the clinical efficacy, safety and tolerability of oral methylprednisolone versus intravenous methylprednisolone for MS relapses in this meta-analysis.Randomized controlled trials (RCTs evaluating the clinical efficacy, safety and tolerability of oral methylprednisolone versus intravenous methylprednisolone for MS relapses were searched in PubMed, Cochrane Library, Medline, EMBASE and China Biology Medicine until October 25, 2016, without language restrictions. The proportion of patients who had improved by day 28 was chosen as the efficacy outcome. We chose the risk ratio (RR to analyze each trial with the 95% confidence interval (95% CI. We also used the fixed-effects model (Mantel-Haenszel approach to calculate the pooled relative effect estimates.A total of 5 trials were identified, which included 369 patients. The results of our meta-analysis revealed that no significant difference existed in relapse improvement at day 28 between oMP and ivMP (RR 0.96, 95% CI 0.84 to 1.10. No evidence of heterogeneity existed among the trials (P = 0.45, I2 = 0%. Both treatments were equally safe and well tolerated except that insomnia was more likely to occur in the oMP group compared to the ivMP group.Our meta-analysis reveals strong evidence that oMP is not inferior to ivMP in increasing the proportion of patients experiencing clinical improvement at day 28. In addition, both routes of administration are equally well tolerated and safe. These findings suggest that we may be able to replace ivMP with oMP to treat MS relapses.

  2. TSH Response to the Intravenous Administration of Synthetic TRH in Various Thyroid Diseases

    International Nuclear Information System (INIS)

    Choi, Sung Jae; Kim, Kwang Won; Lee, Mun Ho

    1980-01-01

    Serum TSH levels were ,measured by radioimmunoassay before and after intravenous administration of synthetic thyrotropin-releasing hormone(TRH) to 15 normal subjects and 55 patients with primary thyroid disease (14 patients with euthyroidism, 24 patients with thyrotoxicosis and 17 patients with hypothyroidism) to evaluate pituitary TSH reserve and its diagnostic availability. The observed results were as follows. 1) In normal subjects, serum TSH responses to synthetic TRH were 3.2±1.0 at 0 min (baseline TSH level), 8.0±4.0 at 10 min, 11.7±5.0 at 20 min, 13.7±7.1 at 80 min, 9.7±5.0 at 60 min., 5.2±2.0 at 120 min. and 3.6±0.4 μU/ml at 180 min. Serum TSH peaked at 20-30 minutes and returned nearly to baseline at 180 minutes. 2) In euthyroid group, serum TSH responses to synthetic TRH were 3.3±1.6 at 0 min, 8.6±8.0 at 10 min, 10.9±8. 5 at 20 min, 12.5±8.4 at 30 min, 9.0±5.9 at 60 min, 5.6±2.6 at 120 min and 3.5±1.3 μU/ml at 180 min. No significant difference revealed between euthyroid group and normal subjects(p>0.05). 3) In hyperthyroid group, serum TSH responses to synthetic TRH were 1.5±0.6 at 0 min, 2.2±0.8 at 10 min., 2.3±1.0 at 20 min., 2.4±1.5 at 30 min., 2.1±1.1 at 60 min,, 1.9±0.2 at 120 min, and 1. 5±0.8 μU/ml, at 180 min., No response to TRH showed. 4) In hypothyroid group, mean values of serum TSH response to synthetic TRH were 42.0 at 0 min., 60.6 at 10 min., 124.8 at 20 min., 123.0 at 30 min. 101.6 at 60 min., 64.3 at 120 min. and 15.5 μU/ml at 180 min., Patients with primary hypothyroidism showed an exaggerated TSH response to synthetic TRH despite their high basal TSH. 5) Side effects attending synthetic TRH administration were transient nausea (59.0%), desire to micturate (59.0%), feeling of flushing (19.7%), dizziness (45.9%), metallic taste (9.8%) and headache (19.7%). Any side effect didn't show in 16.4%. These symptoms began almost immediately after TRH intravenous injection and lasted several minutes, and not related to

  3. TSH Response to the Intravenous Administration of Synthetic TRH in Various Thyroid Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Sung Jae; Kim, Kwang Won; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1980-03-15

    Serum TSH levels were ,measured by radioimmunoassay before and after intravenous administration of synthetic thyrotropin-releasing hormone(TRH) to 15 normal subjects and 55 patients with primary thyroid disease (14 patients with euthyroidism, 24 patients with thyrotoxicosis and 17 patients with hypothyroidism) to evaluate pituitary TSH reserve and its diagnostic availability. The observed results were as follows. 1) In normal subjects, serum TSH responses to synthetic TRH were 3.2+-1.0 at 0 min (baseline TSH level), 8.0+-4.0 at 10 min, 11.7+-5.0 at 20 min, 13.7+-7.1 at 80 min, 9.7+-5.0 at 60 min., 5.2+-2.0 at 120 min. and 3.6+-0.4 muU/ml at 180 min. Serum TSH peaked at 20-30 minutes and returned nearly to baseline at 180 minutes. 2) In euthyroid group, serum TSH responses to synthetic TRH were 3.3+-1.6 at 0 min, 8.6+-8.0 at 10 min, 10.9+-8. 5 at 20 min, 12.5+-8.4 at 30 min, 9.0+-5.9 at 60 min, 5.6+-2.6 at 120 min and 3.5+-1.3 muU/ml at 180 min. No significant difference revealed between euthyroid group and normal subjects(p>0.05). 3) In hyperthyroid group, serum TSH responses to synthetic TRH were 1.5+-0.6 at 0 min, 2.2+-0.8 at 10 min., 2.3+-1.0 at 20 min., 2.4+-1.5 at 30 min., 2.1+-1.1 at 60 min,, 1.9+-0.2 at 120 min, and 1. 5+-0.8 muU/ml, at 180 min., No response to TRH showed. 4) In hypothyroid group, mean values of serum TSH response to synthetic TRH were 42.0 at 0 min., 60.6 at 10 min., 124.8 at 20 min., 123.0 at 30 min. 101.6 at 60 min., 64.3 at 120 min. and 15.5 muU/ml at 180 min., Patients with primary hypothyroidism showed an exaggerated TSH response to synthetic TRH despite their high basal TSH. 5) Side effects attending synthetic TRH administration were transient nausea (59.0%), desire to micturate (59.0%), feeling of flushing (19.7%), dizziness (45.9%), metallic taste (9.8%) and headache (19.7%). Any side effect didn't show in 16.4%. These symptoms began almost immediately after TRH intravenous injection and lasted several minutes, and not related

  4. Time associated with intravenous zoledronic acid administration in patients with breast or prostate cancer and bone metastasis

    Directory of Open Access Journals (Sweden)

    Richhariya A

    2012-02-01

    Full Text Available Akshara Richhariya1, Yi Qian2, Yufan Zhao2, Karen Chung11Amgen Inc, Global Health Economics, Thousand Oaks, CA, USA; 2Amgen Inc, Global Biostatistical Sciences, Thousand Oaks, CA, USAPurpose: Intravenous (IV zoledronic acid (ZA is commonly used to delay skeletal complications secondary to bone metastases. However, the time associated with ZA administration may represent a significant burden to healthcare providers and patients. This study assessed the time associated with IV ZA infusion in patients with bone metastases secondary to breast or prostate cancer (BC or PC in the clinic setting.Methods: Eligible BC or PC patients with bone metastases scheduled to receive IV ZA were observed at seven US-based oncology clinics. Trained observers recorded the time for preinfusion tasks, ZA drug preparation, intravenous infusion, and follow-up activities.Results: Data are reported for 39 patients (BC: 24; PC: 15. Mean administration time was 69 (standard deviation [SD] 42 minutes for all patients combined, 72 (SD 47 minutes for BC, and 65 (SD 33 minutes for PC. Activity times were comparable between tumor types. Mean time for preinfusion tasks (eg, assessment of vital signs, blood draw and ZA preparation were 12 (SD 20 minutes and 2 (SD 1 minutes, respectively. Mean time required for intravenous infusion (ZA infusion and hydration, when provided and follow-up activities were 54 (SD 31 minutes and 2 (SD 1 minutes, respectively.Conclusion: Infusion time was the greatest time commitment associated with IV ZA administration, representing 78% of the total time on average. Time for preinfusion activities varied substantially. Overall, the mean time for ZA administration represents a notable time burden for healthcare providers and patients.Keywords: time and motion, bisphosphonates, zoledronic acid, intravenous administration

  5. 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.)

  6. Foetal Fentanyl Exposure and Ion Trapping after Intravenous and Transdermal Administration to the Ewe.

    Science.gov (United States)

    Heikkinen, Emma M; Kokki, Hannu; Heikkinen, Aki; Ranta, Veli-Pekka; Räsänen, Juha; Voipio, Hanna-Marja; Kokki, Merja

    2017-02-01

    Opioids given to pregnant and parturient women are relatively freely transferred across the placenta. Spinal, epidural and intravenous fentanyl has been studied in pregnant women and neonates, but foetal safety of fentanyl dosing with transdermal patch during pregnancy and labour is not sufficiently studied. Foetal pH is physiologically lower than maternal pH, and thus, opioids, which are weak bases, are ionized and may cumulate to foetus. Foetal asphyxia may further worsen acidosis, and ion trapping induced by low pH is assumed to increase the foetal exposure to opioids. Here, we show that no correlation between foetal acidosis and ion trapping of fentanyl could be found. In three experiments, 29 pregnant sheep were administered fentanyl with 2 μg/kg/h patch supplemented with IV boluses/infusion. Foetal exposure to fentanyl was extensive, median 0.34 ng/ml (quartiles 0.21, 0.42), yet drug accumulation to foetus was not observed, and median of foetal/maternal concentration (F/M) ratio was 0.63 (0.43, 0.75) during the first hours after the fentanyl administration. Low foetal pH and pH difference between ewe and the foetus did not correlate with fentanyl concentration in the foetus or F/M ratio. At steady-state during the second patch worn, foetal plasma fentanyl was low, 0.13 ng/ml, and the median of F/M ratio was 0.69. Our results demonstrate that drug accumulation to foetus caused by ion trapping seen with some weak base opioids may not be that significant with fentanyl. These results have a clinical relevance when fentanyl is dosed to pregnant woman and the foetus is acidemic. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  7. Safety of intravenous tissue plasminogen activator administration with computed tomography evidence of prior infarction.

    Science.gov (United States)

    Lyerly, Michael J; Houston, J Thomas; Boehme, Amelia K; Albright, Karen C; Bavarsad Shahripour, Reza; Palazzo, Paola; Alvi, Muhammed; Rawal, Pawan V; Kapoor, Niren; Sisson, April; Alexandrov, Anne W; Alexandrov, Andrei V

    2014-07-01

    Prior stroke within 3 months excludes patients from thrombolysis; however, patients may have computed tomography (CT) evidence of prior infarct, often of unknown time of origin. We aimed to determine if the presence of a previous infarct on pretreatment CT is a predictor of hemorrhagic complications and functional outcomes after the administration of intravenous (IV) tissue plasminogen activator (tPA). We retrospectively analyzed consecutive patients treated with IV tPA at our institution from 2009-2011. Pretreatment CTs were reviewed for evidence of any prior infarct. Further review determined if any hemorrhagic transformation (HT) or symptomatic intracerebral hemorrhage (sICH) were present on repeat CT or magnetic resonance imaging. Outcomes included sICH, any HT, poor functional outcome (modified Rankin Scale score of 4-6), and discharge disposition. Of 212 IV tPA-treated patients, 84 (40%) had evidence of prior infarct on pretreatment CT. Patients with prior infarcts on CT were older (median age, 72 versus 65 years; P=.001) and had higher pretreatment National Institutes of Health Stroke Scale scores (median, 10 versus 7; P=.023). Patients with prior infarcts on CT did not experience more sICH (4% versus 2%; P=.221) or any HT (18% versus 14%; P=.471). These patients did have a higher frequency of poor functional outcome at discharge (82% versus 50%; P<.001) and were less often discharged to home or inpatient rehabilitation center (61% versus 73%; P=.065). Visualization of prior infarcts on pretreatment CT did not predict an increased risk of sICH in our study and should not be viewed as a reason to withhold systemic tPA treatment after clinically evident strokes within 3 months were excluded. Published by Elsevier Inc.

  8. Compliance with a pediatric clinical practice guideline for intravenous fluid and electrolyte administration.

    Science.gov (United States)

    Hurdowar, Amanda; Urmson, Lynn; Bohn, Desmond; Geary, Denis; Laxer, Ronald; Stevens, Polly

    2009-01-01

    The occurrence of acute hyponatremia associated with cerebral edema in hospitalized children has been increasingly recognized, with over 50 cases of neurological morbidity and mortality reported in the past decade. This condition most commonly occurs in previously healthy children where maintenance intravenous (IV) fluids have been prescribed in the form of hypotonic saline (e.g., 0.2 or 0.3 NaCl). In response to similar problems at The Hospital for Sick Children (six identified through hospital morbidity and mortality reviews and safety reports prior to fall 2007), an interdisciplinary clinician group from our institution developed a clinical practice guideline (CPG) to guide fluid and electrolyte administration for pediatric patients. This article reviews the evaluation of one patient safety improvement to change the prescribing practice for IV fluids in an acute care pediatric hospital, including the removal of the ability to prescribe hypotonic IV solutions with a sodium concentration of < 75 mmol/L. The evaluation of key components of the CPG included measuring practice and process changes pre- and post-implementation. The evaluation showed that the use of restricted IV fluids was significantly reduced across the organization. Success factors of this safety initiative included the CPG development, forcing functions, reminders, team engagement and support from the hospital leadership. A key learning was that a project leader with considerable dedicated time is required during the implementation to develop change concepts, organize and liaise with stakeholders and measure changes in practice. This project highlights the importance of active implementation for policy and guideline documents.

  9. Pharmacokinetics of fluconazole following intravenous and oral administration to koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Black, L A; Krockenberger, M B; Kimble, B; Govendir, M

    2014-02-01

    Clinically normal koalas (n = 12) received a single dose of 10 mg/kg fluconazole orally (p.o.; n = 6) or intravenously (i.v.; n = 6). Serial plasma samples were collected over 24 h, and fluconazole concentrations were determined using a validated HPLC assay. A noncompartmental pharmacokinetic analysis was performed. Following i.v. administration, median (range) plasma clearance (CL) and steady-state volume of distribution (Vss ) were 0.31 (0.11-0.55) L/h/kg and 0.92 (0.38-1.40) L/kg, respectively. The elimination half-life (t1/2 ) was much shorter than in many species (i.v.: median 2.25, range 0.98-6.51 h; p.o.: 4.69, range 2.47-8.01 h), and oral bioavailability was low and variable (median 0.53, range 0.20-0.97). Absorption rate-limited disposition was evident. Plasma protein binding was 39.5 ± 3.5%. Although fluconazole volume of distribution (Varea ) displayed an allometric relationship with other mammals, CL and t1/2 did not. Allometrically scaled values were approximately sevenfold lower (CL) and sixfold higher (t1/2 ) than observed values, highlighting flaws associated with this technique in physiologically distinct species. On the basis of fAUC/MIC pharmacodynamic targets, fluconazole is predicted to be ineffective against Cryptococcus gattii in the koala as a sole therapeutic agent administered at 10 mg/kg p.o. every 12 h. © 2013 John Wiley & Sons Ltd.

  10. Intravenous versus topical tranexamic acid administration in primary total knee arthroplasty: a meta-analysis.

    Science.gov (United States)

    Shin, Young-Soo; Yoon, Jung-Ro; Lee, Hoon-Nyun; Park, Se-Hwan; Lee, Dae-Hee

    2017-11-01

    This meta-analysis was designed to compare the effectiveness and safety of intravenous (IV) versus topical administration of tranexamic acid (TXA) in patients undergoing primary total knee arthroplasty (TKA) by evaluating the need for allogenic blood transfusion, incidence of postoperative complications, volume of postoperative blood loss, and change in haemoglobin levels. Studies were included in this meta-analysis to check whether they assessed the allogenic blood transfusion rate, postoperative complications including pulmonary thromboembolism (PTE) or deep vein thrombosis (DVT), volume of postoperative blood loss via drainage, estimated blood loss, total blood loss, and change in haemoglobin levels before and after surgery in primary TKA with TXA administered through both the IV and topical routes. Ten studies were included in this meta-analysis. The proportion of patients requiring allogenic blood transfusion (OR 1.34, 95 % CI 0.63-2.81; n.s.) and the proportion of patients who developed postoperative complications including PTE or DVT (OR 0.85, 95 % CI 0.41 to 1.77; n.s.) did not significantly differ between the two groups. There was 52.3 mL less blood loss via drainage (95 % CI -50.74 to 185.66 mL; n.s.), 52.1 mL greater estimated blood loss (95 % CI -155.27 to 51.03 mL; n.s.), and 51.4 mL greater total blood loss (95 % CI -208.16 to 105.31 mL; n.s.) in the topical TXA group as compared to the IV TXA group. The two groups were also similar in terms of the change in haemoglobin levels (0.02 g/dL, 95 % CI -0.36 to 0.39 g/dL; n.s.). In primary TKA, there are no significant differences in the transfusion requirement, postoperative complications, blood loss, and change in haemoglobin levels between the IV and topical administration of TXA. In addition, results from subgroup analysis evaluating the effect of the times of TXA administration through the IV route suggested that double IV dose of TXA is more effective than single dose in terms of the

  11. Preliminary Study of Intravenous Amantadine Treatment for Ataxia Management in Patients with Probable Multiple System Atrophy with Predominant Cerebellar Ataxia

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    Jinyoung Youn

    2012-05-01

    Full Text Available Background and Purpose: Multiple system atrophy with predominant cerebellar ataxia is a disabling neurologic disease. However, effective management has not yet been established. We conducted a short-term, open-label preliminary study to assess the benefits of intravenous amantadine treatment in patients with probable multiple system atrophy with predominant cerebellar ataxia. Methods: Twenty patients (10 male, 10 female with probable multiple system atrophy with predominant cerebellar ataxia received 400 mg of amantadine by intravenous per day for 5 days. Ataxia severity was evaluated by the International Cooperative Ataxia Rating Scale before and after intravenous amantadine therapy and all subjects reported subjective improvement after intravenous amantadine treatment using a patient global impression scale. We analyzed the total and subscale scores by the ataxia scale and patient global impression scale. Results: The mean age was 57.4 years (range: 47–72 and the mean disease duration was 30.8 months (range: 11–79. The ataxia severity significantly decreased after intravenous amantadine therapy from 42.5 to 37.3 (p < 0.001. The mean patient global impression scale for improvement was 2.9 and there were no side effects of intravenous amantadine treatment observed. When we assessed responders, the duration of intravenous amantadine effect was more than 1 month in 4 subjects of 7 responders. Conclusions: Our findings suggest that intravenous amantadine treatment can be a safe management option in cerebellar ataxia, although the mechanism is unclear. Thus, further double-blind, long-term studies with a larger sample size are needed.

  12. Administrative risk quantification of subcutaneous and intravenous therapies in Italian centers utilizing the Failure Mode and Effects Analysis approach

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    Ponzetti C

    2016-08-01

    Full Text Available Clemente Ponzetti,1 Monica Canciani,2 Massimo Farina,2 Sara Era,3 Stefan Walzer4,5 1Gruppo Policlinico di Monza, Alessandria, ANMDO National Association of Hospital Physicians, Bologna, 2Studio EmmEffe Srl, Milan, 3Roche Spa, Monza, Italy; 4MArS Market Access & Pricing Strategy GmbH, Weil am Rhein, 5State University Baden-Wuerttemberg, Health Care Management, Loerrach, Germany Background: In oncology, an important parameter of safety is the potential treatment error in hospitals. The analyzed hypothesis is that of subcutaneous therapies would provide a superior safety benefit over intravenous therapies through fixed-dose administrations, when analyzed with trastuzumab and rituximab.Methods: For the calculation of risk levels, the Failure Mode and Effect Analysis approach was applied. Within this approach, the critical treatment path is followed and risk classification for each individual step is estimated. For oncology and hematology administration, 35 different risk steps were assessed. The study was executed in 17 hematology and 16 breast cancer centers in Italy. As intravenous and subcutaneous were the only injection routes in medical available for trastuzumab and rituximab in oncology at the time of the study, these two therapies were chosen.Results: When the risk classes were calculated, eight high-risk areas were identified for the administration of an intravenous therapy in hematology or oncology; 13 areas would be defined as having a median-risk classification and 14 areas as having a low-risk classification (total risk areas: n=35. When the new subcutaneous formulation would be applied, 23 different risk levels could be completely eliminated (65% reduction. Important high-risk classes such as dose calculation, preparation and package labeling, preparation of the access to the vein, pump infusion preparation, and infusion monitoring were included in the eliminations. The overall risk level for the intravenous administration was estimated

  13. Influence of intravenous self-administered psychomotor stimulants on performance of rhesus monkeys in a multiple schedule paradigm.

    Science.gov (United States)

    Hoffmeister, F

    1980-01-01

    Rhesus monkeys were trained to complete three multiple schedules. The schedules consisted of three components: a fixed interval (component 1), a variable interval (component 2), and a fixed ratio (component 3). During components 1 and 2, pressing lever 1 was always reinforced by food delivery. During component 3, pressing lever 2 resulted in either food delivery or intravenous infusions of saline solution, solutions of cocaine, of d-amphetamine, of phenmetrazine, or fenetylline. In schedule I, animals were presented with all three components independent of key-pressing behavior during components 1 and 2. In schedule II the availability of component 2 was dependent on completion of component 1. Component 3 was made available only on completion of component 2. Noncompletion of components 1 or 2 resulted in time-out of 15 and 10 min, respectively. Schedule III was identical with schedule II, except that in schedule III the completion of components was indicated only by a change in the lever lights. The influence of self-administered drugs on behavior in all three components was evaluated. Self-administration of psychomotor stimulants impaired the performance of animals and delayed completion of components 1 and 2 of schedules I, II, and III. The effects on behavior were similar with low drug intake in schedule III, moderate intake in schedule II, and high drug intake in schedule I. These effects were strong with self-administration of phenmetrazine, moderate with self-administration of cocaine and d-amphetamine, and weak with self-administration of fenetylline.

  14. C-Psilocin tissue distribution in pregnant rats after intravenous administration

    Directory of Open Access Journals (Sweden)

    Francis C.P. Law

    2014-06-01

    Full Text Available Background: Many species of hallucinogenic mushrooms have been found in the genus Psilocybe. The main psychoactive chemicals of Psilocybe mushrooms are psilocin and its phosphoryloxy derivative, psilocybin. In addition to its psychedelic effects, psilocybin is an effective agent to lift the mood of depressed patients with terminal cancers. Objective: To study the dispositional kinetics of 14C-psilocin in pregnant rats after intravenous injection, to calculate tissue dose surrogates i.e., tissue 14C concentration and area under the concentration-time curve using the experimental data, to quantify trans-placental passage of psilocin and/or its metabolites, and to identify new psilocin metabolite(s in rat urine. Methods: A group of 15 pregnant Wistar rats weighing between 0.30-0.36 kg was used in the study. Each rat was given a single dose of 7.5 mg/kg 14C-psilocin i.v. Three rats were randomly selected and sacrificed at 0.5, 1.0, 2.0, 4.0, and 8.0 hr post-dosing. The maternal and fetal tissues were quickly removed and the radioactivity in these tissues determined by liquid scintillation counting. In a separate study, urine samples were collected from 6 male Wistar rats after administering 15 mg/kg of unlabeled psilocin i.p. The urine samples were collected and extracted by chloroform-methanol (9:1 v/v and analyzed using a gas chromatograph/mass spectrometer. Results: 14C-Psilocin crossed the placental barrier of pregnant rats readily after i.v. administration; maternal tissue 14C concentrations were found to be much higher than those in fetal tissues. The areas under the curve for maternal tissues also were much higher than the fetal tissues. In general, maternal tissues could be divided into the fast eliminating organ group, which included the brain (elimination half-life 13 hr. A new psilocin metabolite tentatively identified as dihydroxyindoleacetic acid was found in the urine. Conclusion: Our study showed that psilocin readily crossed the

  15. Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial

    DEFF Research Database (Denmark)

    Fazekas, F.; Lublin, F.D.; Li, D.

    2008-01-01

    OBJECTIVE: Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. W...

  16. Intravenous administration of levothyroxine for treatment of suspected myxedema coma complicated by severe hypothermia in a dog.

    Science.gov (United States)

    Henik, R A; Dixon, R M

    2000-03-01

    A 7-year-old male English Coonhound with suspected myxedema coma complicated by severe hypothermia and metabolic abnormalities was treated with a combination of active external and core rewarming techniques, i.v. and oral administration of levothyroxine, supplemental oxygen, and administration of fluids (0.9% NaCl solution). Myxedema coma develops as a consequence of severe hypothyroidism and is characterized by a hypometabolic, stuporous state. Myxedema coma is associated with a high mortality rate, and most reported cases have involved Doberman Pinschers. Intravenous administration of levothyroxine can be used successfully in combination with oral administration to restore normal metabolic function and assist in warming and thermoregulation, although dosages should be conservative to avoid adverse cardiovascular effects.

  17. Intravenous administration of stabilized antisense lipid particles (SALP) leads to activation and expansion of liver natural killer cells.

    Science.gov (United States)

    Bramson, J L; Bodner, C A; Johnson, J; Semple, S; Hope, M J

    2000-06-01

    Stabilized antisense lipid particles (SALP) have been developed for the systemic delivery of oligonucleotides. The impact of intravenous SALP administration was measured with respect to activation of natural killer (NK) and NK1.1+ T (NKT) cells in the livers of immunocompetent mice. Treatment with a SALP containing a highly mitogenic oligonucleotide (INX-6295) generated an increase in NK cytolytic activity and cell number within the liver but did not appear to affect the number of hepatic NKT cells or their cytolytic activity. The same results were observed after intravenous administration of the mitogenic oligonucleotide alone. Interestingly, treatment with a SALP containing a weakly mitogenic oligonucleotide (INX-6300) also activated the liver NK cells, whereas the oligonucleotide alone was unable to elicit these effects. The NK stimulatory activity of a SALP containing INX-6300 required both lipid and oligonucleotide components. These results demonstrate that in addition to modifying the pharmacokinetics and biodistribution of intravenously administered oligonucleotides, SALP possess immunostimulatory activity independent of oligonucleotide mitogenicity, which can serve as an adjuvant to antisense therapies for cancer.

  18. Absence of analgesic effect of intravenous melatonin administration during daytime after laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Kücükakin, Bülent; Werner, Mads U

    2014-01-01

    mg of intravenous (IV) melatonin or placebo were administered at the time of surgical incision. MEASUREMENTS: Pain was assessed by a set of questionnaires documenting "pain at rest" using a visual analog scale (VAS). The use of rescue medication was recorded. Sleep quality and general well-being were...

  19. Administration of gentamicin and ampicillin by continuous intravenous infusion to newborn infants during parenteral nutrition

    DEFF Research Database (Denmark)

    Colding, H; Andersen, G E

    1982-01-01

    Gentamicin and ampicillin were dissolved in an L-amino acid solution especially prepared for newborn infants and infused intravenously over 24 h in 7 babies with serious neonatal surgical problems. Serum concentrations of the antibiotics were maintained rather constant and well above the minimal ...

  20. Intravenøs administration af lipid ved forgiftning med lipofilt laegemiddel

    DEFF Research Database (Denmark)

    Skjønnemand, Martin; Damgaard-Jensen, Jens; Gottschau, Bo

    2011-01-01

    OBJECTIVE: To draw attention to the use of intravenous lipids in the treatment of cardiac arrests caused by overdosage of lipophilic drugs. Case reports and animal studies have shown beneficial use of lipids in severe intoxication. The literature is reviewed. CONCLUSION: Lipids have a place in th...

  1. Evaluation of lipid peroxidation activity at intravenous administration of gold nanorods in rats with simulated diabetes and transplanted liver cancer

    Science.gov (United States)

    Bucharskaya, Alla B.; Dikht, Natalia I.; Afanasyeva, Galina A.; Terentyuk, Georgy S.; Maslyakova, Galina N.; Zaraeva, Nadezhda V.; Khlebtsov, Nikolai G.; Khlebtsov, Boris N.

    2014-01-01

    In the experiment the white outbred rats with transplanted liver cancer (cholangiocarcinoma line PC-1) and simulated alloxan diabetes were treated by single intravenous injection of gold nanorods. State of lipid peroxidation was evaluated by the following parameters: the malondialdehyde, lipid hydroperoxide, the average weght molecules in the serum of animals by conventional spectrophotometric methods study using a spectrofluorometer RF-5301 PC (Shimadzu, Japan). In both experimental groups of animals the significant increasing of levels of lipid peroxidation products was noted compared with control group. After intravenous administration of nanoparticles in the group of animals with alloxan diabetes the activation of a free radical oxidation was not observed, in group with transplanted liver cancer the increasing of levels of lipid hydroperoxide, malondialdehyde was established.

  2. Endogenous stem cell proliferation induced by intravenous hedgehog agonist administration after contusion in the adult rat spinal cord.

    Science.gov (United States)

    Bambakidis, Nicholas C; Horn, Eric M; Nakaji, Peter; Theodore, Nicholas; Bless, Elizabeth; Dellovade, Tammy; Ma, Chiyuan; Wang, Xukui; Preul, Mark C; Coons, Stephen W; Spetzler, Robert F; Sonntag, Volker K H

    2009-02-01

    Sonic hedgehog (Shh) is a glycoprotein molecule that upregulates the transcription factor Gli1. The Shh protein plays a critical role in the proliferation of endogenous neural precursor cells when directly injected into the spinal cord after a spinal cord injury in adult rodents. Small-molecule agonists of the hedgehog (Hh) pathway were used in an attempt to reproduce these findings through intravenous administration. The expression of Gli1 was measured in rat spinal cord after the intravenous administration of an Hh agonist. Ten adult rats received a moderate contusion and were treated with either an Hh agonist (10 mg/kg, intravenously) or vehicle (5 rodents per group) 1 hour and 4 days after injury. The rats were killed 5 days postinjury. Tissue samples were immediately placed in fixative. Samples were immunohistochemically stained for neural precursor cells, and these cells were counted. Systemic dosing with an Hh agonist significantly upregulated Gli1 expression in the spinal cord (p < 0.005). After spinal contusion, animals treated with the Hh agonist had significantly more nestin-positive neural precursor cells around the rim of the lesion cavity than in vehicle-treated controls (means +/- SDs, 46.9 +/- 12.9 vs 20.9 +/- 8.3 cells/hpf, respectively, p < 0.005). There was no significant difference in the area of white matter injury between the groups. An intravenous Hh agonist at doses that upregulate spinal cord Gli1 transcription also increases the population of neural precursor cells after spinal cord injury in adult rats. These data support previous findings based on injections of Shh protein directly into the spinal cord.

  3. High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine.

    Science.gov (United States)

    Motbey, Craig P; Clemens, Kelly J; Apetz, Nadine; Winstock, Adam R; Ramsey, John; Li, Kong M; Wyatt, Naomi; Callaghan, Paul D; Bowen, Michael T; Cornish, Jennifer L; McGregor, Iain S

    2013-09-01

    Mephedrone (MMC) is a relatively new recreational drug that has rapidly increased in popularity in recent years. This study explored the characteristics of intravenous MMC self-administration in the rat, with methamphetamine (METH) used as a comparator drug. Male Sprague-Dawley rats were trained to nose poke for intravenous MMC or METH in daily 2 h sessions over a 10 d acquisition period. Dose-response functions were then established under fixed- and progressive-ratio (FR and PR) schedules over three subsequent weeks of testing. Brains were analyzed ex vivo for striatal serotonin (5-HT) and dopamine (DA) levels and metabolites, while autoradiography assessed changes in the regional density of 5-HT and serotonin transporter (SERT) and DA transporter (DAT) and induction of the inflammation marker translocator protein (TSPO). Results showed that MMC was readily and vigorously self-administered via the intravenous route. Under a FR1 schedule, peak responding for MMC was obtained at 0.1 mg/kg/infusion, versus 0.01 mg/kg/infusion for METH. Break points under a PR schedule peaked at 1 mg/kg/infusion MMC versus 0.3 mg/kg/infusion for METH. Final intakes of MMC were 31.3 mg/kg/d compared to 4 mg/kg/d for METH. Rats self-administering MMC, but not METH, gained weight at a slower rate than control rats. METH, but not MMC, self-administration elevated TSPO receptor density in the nucleus accumbens and hippocampus, while MMC, but not METH, self-administration decreased striatal 5-hydroxyindolacetic acid (5-HIAA) concentrations. In summary, MMC supported high levels of self-administration, matching or exceeding those previously reported with other drugs of abuse.

  4. Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Paul W Denton

    2010-01-01

    Full Text Available Successful antiretroviral pre-exposure prophylaxis (PrEP for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT. BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003 and intravenous (Chi square = 13, df = 1, p = 0.0003 HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS.

  5. Nalfurafine hydrochloride, a selective κ opioid receptor agonist, has no reinforcing effect on intravenous self-administration in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Kaoru Nakao

    2016-01-01

    Full Text Available Nalfurafine hydrochloride [(E-N-[17-(cyclopropylmethyl-4,5α-epoxy-3,14-dihydroxymorphinan-6β-yl]-3-(furan-3-yl-N-methylprop-2-enamide monohydrochloride; nalfurafine] is used in Japan as an antipruritic for the treatment of intractable pruritus in patients undergoing hemodialysis or with chronic liver disease. It is a potent and selective agonist at the κ opioid receptor, but also has weak and partial agonist activity at μ opioid receptors. Opioids, especially those acting at μ receptors, carry a risk of abuse. This is an important factor in the consideration of therapeutic risk vs. benefit in clinical use and the potential for misuse as a public health problem. It is therefore necessary to carefully evaluate the reinforcing effects of nalfurafine. To this end, we investigated intravenous self-administration of nalfurafine in rhesus monkeys. The number of self-administration of nalfurafine at doses of 0.0625, 0.125 and 0.25 μg/kg/infusion was not higher than that of saline in rhesus monkeys that frequently self-administered pentazocine (0.25 mg/kg/infusion. These results indicate that nalfurafine has no reinforcing effect in rhesus monkeys in the intravenous self-administration paradigm.

  6. Bidirectional Tachycardia after an Acute Intravenous Administration of Digitalis for a Suicidal Gesture

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    Diletta Sabatini

    2014-01-01

    Full Text Available Acute digoxin intoxication is a life-threating condition associated with severe cardiotoxicity. Female gender, age, low lean body mass, hypertension, and renal insufficiency may worsen the prognosis. Arrhythmias caused by digitalis glycosides are characterized by an increased automaticity coupled with concomitant conduction delay. Bidirectional tachycardia is pathognomonic of digoxin intoxication, but it is rarely observed. An 83-year-old woman was admitted to the Emergency Department after self-administration of 5 mg of digoxin i.v. for suicidal purpose. Her digoxin serum concentration was 17.4 ng/mL. The patient developed a bidirectional tachycardia and the Poison Control Center of the hospital provided digoxin immune fab. Bidirectional tachycardia quickly reversed and the patient remained stable throughout the hospital stay. This case shows that a multiple disciplinary approach, involving cardiologists and toxicologists, is essential for the management of digoxin intoxication. The optimal treatment of this rare event depends on the clinical conditions and on the serum drug concentration of the patient. Digoxin immune fab represents a safe, effective, and specific method for rapidly reversing digitalis cardiotoxicity and should be started as soon as the diagnosis is defined.

  7. Effect of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold, following intravenous or buccal administration to cats.

    Science.gov (United States)

    Pypendop, Bruno H; Shilo-Benjamini, Yael; Ilkiw, Jan E

    2016-11-01

    To determine the effects of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold in cats, following buccal and intravenous (IV) administration. Randomized crossover study. Six healthy adult female ovariohysterectomized cats weighing 4.5 ± 0.4 kg. Morphine sulfate (0.2 mg kg -1 IV or 0.5 mg kg -1 buccal), methadone hydrochloride (0.3 mg kg -1 IV or 0.75 mg kg -1 buccal), hydromorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) or oxymorphone hydrochloride (0.1 mg kg -1 IV or 0.25 mg kg -1 buccal) were administered. All cats were administered all treatments. Skin temperature and thermal threshold were measured in duplicate prior to drug administration, and at various times up to 8 hours after drug administration. The difference between thermal threshold and skin temperature (ΔT) was analyzed. Administration of methadone and hydromorphone IV resulted in significant increases in ΔT at 40 minutes after drug administration. Buccal administration of methadone resulted in significant increases in thermal threshold, although no significant difference from baseline measurement was detected at any time point. IV administration of morphine and oxymorphone, and buccal administration of morphine, hydromorphone and oxymorphone did not cause significant thermal antinociception. At the doses used in this study, IV administration of methadone and hydromorphone, and buccal administration of methadone resulted in transient thermal antinociception. The results of this study do not allow us to predict the usefulness of these drugs for providing analgesia in clinical patients. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  8. 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.

  9. Pharmacokinetics and effects on thromboxane B2 production following intravenous administration of flunixin meglumine to exercised thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Arthur, R M; McKemie, D S; Chapman, N

    2015-08-01

    Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS). An additional objective was to characterize the effects of flunixin on COX-1 and COX-2 inhibition when drug concentrations reached the recommended regulatory threshold. Sixteen exercised adult horses received a single intravenous dose of 1.1 mg/kg. Blood samples were collected up to 72 h postadministration and analyzed using LC-MS. Blood samples were collected from 8 horses for determination of TxB(2) and PGE(2) concentrations prior to and up to 96 h postflunixin administration. Mean systemic clearance, steady-state volume of distribution and terminal elimination half-life was 0.767 ± 0.098 mL/min/kg, 0.137 ± 0.12 L/kg, and 4.8 ± 1.59 h, respectively. Four of the 16 horses had serum concentrations in excess of the current ARCI recommended regulatory threshold at 24 h postadministration. TxB(2) suppression was significant for up to 24 h postadministration. © 2015 John Wiley & Sons Ltd.

  10. The disposition of 3H-aflatoxin B1 in the rainbow trout (Oncorhynchys mykiss) after oral and intravenous administration

    International Nuclear Information System (INIS)

    Ngethe, S.; Horsberg, T.E.; Ingebrigtsen, K.

    1992-01-01

    The disposition of tritiated aflatoxin B1 in the rainbow trout following oral and intravenous administration was studied over a period of 8 days by means of liquid scintillation counting and whole-body autoradiography. The pattern of distribution together with the quantitative measurements were fairly similar in both groups, indicating a high degree of gastrointestinal absorption. The highest concentrations of radioactivity were observed in the bile, liver, kidney, pyloric caeca, uveal tract of the eye and the olfactory rosette. Substantial amounts of radioactivity were still present in the liver, kidney, olfactory rosette and the mucosa of the pyloric caeca 8 days after administration. A major fraction of this radioactivity was not extractable with certain polar and nonpolar solvents, indicating covalently bound metabolites

  11. Pharmacokinetics of nalbuphine hydrochloride after intravenous and intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Keller, Dominique L; Sanchez-Migallon Guzman, David; Klauer, Julia M; KuKanich, Butch; Barker, Steven A; Rodríguez-Ramos Fernández, Julia; Paul-Murphy, Joanne R

    2011-06-01

    To assess the pharmacokinetics of nalbuphine HCl after IV and IM administration to Hispaniolan Amazon parrots (Amazona ventralis). 8 healthy adult Hispaniolan Amazon parrots of unknown sex. Nalbuphine HCl (12.5 mg/kg) was administered IV and IM to all birds in a complete randomized crossover study design; there was a washout period of 21 days between subsequent administrations. Plasma samples were obtained from blood collected at predetermined time points for measurement of nalbuphine concentration by use of liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by use of computer software. Nalbuphine was rapidly eliminated with a terminal half-life of 0.33 hours and clearance of 69.95 mL/min/kg after IV administration and a half-life of 0.35 hours after IM administration. Volume of distribution was 2.01 L/kg after IV administration. The fraction of the dose absorbed was high (1.03) after IM administration. No adverse effects were detected in the parrots during the study. In Hispaniolan Amazon parrots, nalbuphine appeared to have good bioavailability after IM administration and was rapidly cleared after IV and IM administration. Safety and analgesic efficacy of various nalbuphine treatment regimens in this species require further investigation to determine the potential for clinical palliation of signs of pain in psittacine species.

  12. Corneal pharmacokinetics of the 2% diacerein eye drops between multiple administration and single administration

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    Ke Yang

    2018-04-01

    Full Text Available AIM: To compare the pharmacokinetic differences of the 2% diacerein eye drops between conjunctival sac multiple administration and single administration in the cornea, and to provide the experimental basis for clinicians to use the conjunctival sac multiple administration.METHODS: Male Kunming mice were randomly divided into the multiple administration group and the single administration group. The multiple administration group were given diacerein eye drop every 2min(3 times in total. The concentrations of the metabolites of diacerein in the cornea were measured by high performance liquid chromatography after given eye drop 5, 15, 30, 60, 120, and 180min. The pharmacokinetic parameters were calculated by pharmacokinetic software(DAS2.1.1. RESULTS: The metabolites of diacerein, rhein, was detected in the cornea at each time point. The concentration of the metabolite of diacerein in the cornea was 318.678±40.88, 210.02±25.66, 188.83±31.74, 112.24±11.70, 90.28±22.01 and 57.67±13.71μg/g after given eye drop 5, 15, 30, 60, 120, and 180min in the multiple administration group. The concentration in the single administration group was 145.17±19.29, 97.95±10.49, 71.18±18.70, 39.11±2.44, 18.10±2.34 and 9.08±2.04μg/g respectively. The concentration of rhein in the cornea was the highest at 5min after the administration in the two groups. The concentration of the multiple administration group was higher than that in the single administration group at 5, 15, 30, 60, 120, and 180min(PCONCLUSION: Compared with the single administration, the conjunctival sac multiple administration has the advantages of high drug concentration and long duration. Therefor the conjunctival sac multiple administration is a more effective method to treat acute infectious corneal diseases.

  13. Pharmacokinetic evaluation of Shenfu Injection in beagle dogs after intravenous drip administration

    Directory of Open Access Journals (Sweden)

    Yuqiao Zhang

    2016-10-01

    Full Text Available Shenfu Injection (SFI is a well-defined Chinese herbal formulation that is obtained from red ginseng and processed aconite root. The main active constituents in SFI are ginsenosides and aconitum alkaloids. In this work, ginsenosides (ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rc and aconitum alkaloids (benzoylmesaconine and fuziline were used as the index components to explore the pharmacokinetic behavior of SFI. A selective and sensitive HPLC–MS/MS method was developed for the quantification of ginsenosides and aconitum alkaloids in dog plasma and was used to characterize the pharmacokinetics of the five index components after intravenous drip of three different dosages of SFI in beagle dogs. The pharmacokinetic properties of the index components were linear over the dose range of 2–8 mL/kg.

  14. Sublingual administration of detomidine to calves prior to disbudding: a comparison with the intravenous route.

    OpenAIRE

    Hokkanen, Ann-Helena; Raekallio, Marja R.; Salla, Kati; Hänninen, Laura; Viitasaari, Elina Anna Maria; Norring, Marianna; Raussi, Satu; Rinne, Valtteri; Scheinin, Mika; Vainio, Outi M.

    2014-01-01

    Objective To study the effects of oromucosal detomidine gel administered sublingually to calves prior to disbudding, and to compare its efficacy with intravenously (IV) administered detomidine. Study design Randomised, prospective clinical study. Animals Twenty dairy calves aged 12.4 ± 4.4days (mean ± SD), weight 50.5 ± 9.0 kg. Methods Detomidine at 80 μg kg−1 was administered to ten calves sublingually (GEL) and at 30 μg kg−1 to ten control calves IV (V. jugularis). Meloxicam (0.5 mg kg−1) a...

  15. 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

  16. 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

  17. Antinociceptive effects of tramadol hydrochloride after intravenous administration to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Geelen, Saskia; Sanchez-Migallon Guzman, David; Souza, Marcy J; Cox, Sherry; Keuler, Nicholas S; Paul-Murphy, Joanne R

    2013-02-01

    To determine the antinociceptive and sedative effects of tramadol in Hispaniolan Amazon parrots (Amazona ventralis) following IV administration. 11 healthy Hispaniolan Amazon parrots of unknown sex. Tramadol hydrochloride (5 mg/kg, IV) and an equivalent volume (≤ 0.34 mL) of saline (0.9% NaCl) solution were administered to parrots in a complete crossover study design. Foot withdrawal response to a thermal stimulus was determined 30 to 60 minutes before (baseline) and 15, 30, 60, 120, and 240 minutes after treatment administration; agitation-sedation scores were determined for parrots at each of those times. The estimated mean changes in temperature from the baseline value that elicited a foot withdrawal response were 1.65° and -1.08°C after administration of tramadol and saline solution, respectively. Temperatures at which a foot withdrawal response was elicited were significantly higher than baseline values at all 5 evaluation times after administration of tramadol and were significantly lower than baseline values at 30, 120, and 240 minutes after administration of saline solution. No sedation, agitation, or other adverse effects were observed in any of the parrots after administration of tramadol. Tramadol hydrochloride (5 mg/kg, IV) significantly increased the thermal nociception threshold for Hispaniolan Amazon parrots in the present study. Sedation and adverse effects were not observed. These results are consistent with results of other studies in which the antinociceptive effects of tramadol after oral administration to parrots were determined.

  18. Intravenous application of HI-6 salts (dichloride and dimethansulphonate) in pigs: comparison with pharmacokinetics profile after intramuscular administration.

    Science.gov (United States)

    Zdarova Karasova, Jana; Zemek, Filip; Kunes, Martin; Kvetina, Jaroslav; Chladek, Jaroslav; Jun, Daniel; Bures, Jan; Tachecí, Ilja; Kuca, Kamil

    2013-01-01

    Oxime HI-6 is an acetylcholinesterase reactivator therapeutically efficient against nerve agents. Because of their physico-chemical properties, oximes are typically applied intramuscularly (i.m.). This route of administration has also some disadvantages, and alternative strategies ought to be examined. We evaluated the pharmacokinetic profiles of two HI-6 salts after their intravenous (i.v.) administration, and compare the results with the known pharmacokinetics after i.m. administration. Pigs were administered with HI-6 salts (i.v), either HI-6 dichloride (10.71 mg/kg) or molar equivalent HI-6 dimethansulphonate (13.59 mg/kg). Doses of the HI-6 salts corresponded with a standard HI-6 dichloride dose in one autoinjector (500 mg) and were recalculated for one kilogram of body weight. The main pharmacokinetic parameters are comparable after i.v. and i.m. HI-6 administration. The compared pharmacokinetic parameters were half-life, terminal rate constant, mean residence time of the molecule in the body, clearance, and the apparent volume in the terminal phase. The bioavailability after i.m. administration was comparable with that of i.v.; these results suggest that the oxime is well released from the muscle depot. Significant differences were found in parameters Cmax and Tmax which are important in cases of emergency when rapidity and bioavailability are paramount for the success of treatment. I.v. administration should solve the problem of rapid clearance. Infusion or bolus administration may be considered as a logical subsequent step in oxime treatment strategy. The main advantage is in maintenance of an effective therapeutic plasma concentration, a more easily achievable effective therapeutic concentration, and fewer local adverse reactions.

  19. Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats.

    Science.gov (United States)

    Rodrigo-Mocholí, D; Escudero, E; Belda, E; Laredo, F G; Hernandis, V; Marín, P

    2018-07-01

    To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats. Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two-treatment, two-period study. Alfaxalone at a dose of 5 mg/kg was administered either I/V or I/M. Blood samples were collected between 2-480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5-120 minutes after drug administration using a numerical rating scale (from 0-18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded. The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (pV (0 minutes for all animals) treated cats (p15) were recorded from 5-15 minutes after I/V administration and deep sedation (scores 11-15) at 20 and 30 minutes. Deep sedation was observed from 10-45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery. Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.

  20. Successful management of ivermectin-induced blindness in an African lion (Panthera leo) by intravenous administration of a lipid emulsion.

    Science.gov (United States)

    Saqib, Muhammad; Abbas, Ghazanfar; Mughal, Mudassar Niaz

    2015-11-26

    Ivermectin is widely used in veterinary practice for the treatment of ecto- and endo-parasites. In wildlife, an extra-label use this parasiticide is sometimes associated with toxicity. Different treatment regimens have been used in ivermectin toxicosis. The present report describes a successful reversal of ivermectin toxicity by intravenous administration of a commercially available lipid emulsion in a captive African lion (Panthera leo). A 2-year old captive African lion (Panthera leo) weighing ~130 kg was presented with acute neurological impairment and bilateral blindness that had developed 24 h after ivermectin exposure. The animal was treated with a commercially available lipid emulsion along with supportive therapy and experienced complete recovery. To our knowledge, this is the first case report of the use of lipid emulsion in the management of ivermectin induced blindness in an African lion and it appears that intravenous lipid emulsion may be an effective therapy in ivermectin toxicity in lions. Further testing in expanded clinical trials is clearly warranted.

  1. Milk iron content in breast-feeding mothers after administration of intravenous iron sucrose complex.

    Science.gov (United States)

    Breymann, Christian; von Seefried, Bettina; Stahel, Michele; Geisser, Peter; Canclini, Camillo

    2007-01-01

    To study the transfer of parenteral iron sucrose into maternal milk in the postpartum period. Ten healthy lactating mothers with functional iron deficiency 2-3 days after delivery received 100 mg intravenous iron sucrose and were observed together with a control group (n=5) without iron treatment during four days. Milk samples were taken before the treatment and every day afterwards. Mean milk iron levels at baseline were 0.43 and 0.46 mg/kg in the treatment and control group and decreased until the end of observation in both groups by 0.11 mg/kg. No significant difference between the groups was found on any study day as well as in the mean change from baseline over all four days. We could not show transfer of iron-sucrose into maternal milk for the given dosage. Since parenteral iron sucrose is widely used in obstetrics, the results provide information about safety of parenteral iron sucrose in the lactation period. The findings are also in agreement with other reports on active biological mammary gland regulation of milk iron concentration.

  2. Cerebral Microvascular and Systemic Effects Following Intravenous Administration of the Perfluorocarbon Emulsion Perftoran.

    Science.gov (United States)

    Abutarboush, Rania; Saha, Biswajit K; Mullah, Saad H; Arnaud, Francoise G; Haque, Ashraful; Aligbe, Chioma; Pappas, Georgina; Auker, Charles R; McCarron, Richard M; Moon-Massat, Paula F; Scultetus, Anke H

    2016-11-18

    Oxygen-carrying perfluorocarbon (PFC) fluids have the potential to increase tissue oxygenation during hypoxic states and to reduce ischemic cell death. Regulatory approval of oxygen therapeutics was halted due to concerns over vasoconstrictive side effects. The goal of this study was to assess the potential vasoactive properties of Perftoran by measuring brain pial arteriolar diameters in a healthy rat model. Perftoran, crystalloid (saline) or colloid (Hextend) solutions were administered as four sequential 30 min intravenous (IV) infusions, thus allowing an evaluation of cumulative dose-dependent effects. There were no overall changes in diameters of small-sized (<50 μm) pial arterioles within the Perftoran group, while both saline and Hextend groups exhibited vasoconstriction. Medium-sized arterioles (50-100 μm) showed minor (~8-9%) vasoconstriction within saline and Hextend groups and only ~5% vasoconstriction within the Perftoran group. For small- and medium-sized pial arterioles, the mean percent change in vessel diameters was not different among the groups. Although there was a tendency for arterial blood pressures to increase with Perftoran, pressures were not different from the other two groups. These data show that Perftoran, when administered to healthy anesthetized rats, does not cause additional vasoconstriction in cerebral pial arterioles or increase systemic blood pressure compared with saline or Hextend.

  3. Roux-en-Y gastric bypass increases intravenous ethanol self-administration in dietary obese rats.

    Directory of Open Access Journals (Sweden)

    James E Polston

    Full Text Available Roux-en-Y gastric bypass surgery (RYGB is an effective treatment for severe obesity. Clinical studies however have reported susceptibility to increased alcohol use after RYGB, and preclinical studies have shown increased alcohol intake in obese rats after RYGB. This could reflect a direct enhancement of alcohol's rewarding effects in the brain or an indirect effect due to increased alcohol absorption after RGYB. To rule out the contribution that changes in alcohol absorption have on its rewarding effects, here we assessed the effects of RYGB on intravenously (IV administered ethanol (1%. For this purpose, high fat (60% kcal from fat diet-induced obese male Sprague Dawley rats were tested ~2 months after RYGB or sham surgery (SHAM using both fixed and progressive ratio schedules of reinforcement to evaluate if RGYB modified the reinforcing effects of IV ethanol. Compared to SHAM, RYGB rats made significantly more active spout responses to earn IV ethanol during the fixed ratio schedule, and achieved higher breakpoints during the progressive ratio schedule. Although additional studies are needed, our results provide preliminary evidence that RYGB increases the rewarding effects of alcohol independent of its effects on alcohol absorption.

  4. MRI evaluation of osteonecrosis in knee joints after intravenous administration of corticosteroids in patients with severe acute respiratory syndrome

    International Nuclear Information System (INIS)

    Gao Yong'an; Liu Hualiang; Dong Yanqing; Liu Ying; Li Kuncheng; Wang Zhongwei; Li Ping

    2005-01-01

    Objective: To evaluate MRI features of osteonecrosis in knee joints after intravenous administration of exogenous corticosteroids in patients with severe acute respiratory syndrome (SARS). Methods: MRI was done in 18 patients (medical staff from 4 hospitals) suffered from SARS and treated with intravenous use of exogenous corticosteroids in hip joints and knee joints to indicate the findings and characteristics of osteonecrosis as well as their relation with hormone amount. Results: Eleven patients showed lesions of osteonecrosis in knee joints with bilateral in 7 and unilateral in 4, and 3 patients were complicated with avascular necrosis in bilateral femoral heads. Among the 38 lesions in knee joints, 34 lesions were located in medial condylu, lateral condylus and shaft of femur, and 4 in medial condylus or lateral condylus of tibia. Large-middle lesions showed geographic focus of typically heterogeneous signal (low or intermediate signal intensity on T 1 WI and high or intermediate signal intensity T 2 WI) within the marrow that was surrounded by characteristic low signal intensity, serpentine border on T 1 , T 2 WI. This border showed a classic double-line sign on T 2 WI in 4 lesions. Small lesions showed low signal intensity on T 1 and low or high signal intensity on T 2 WI. Subchondral avascular necrosis in middle-upper femoral heads showed intermediate signal intensity on T 1 weighted images and high or complicated signal intensity on T 2 WI encircled with characteristic low signal intensity, serpentine border on T 1 and T 2 WI. This border showed a classic double-line sign on T 2 weighted images in avascular necrosis of bilateral femoral heads in 1 case. Conclusion: In these cases, osteonecrosis in knee joints was more than in femoral heads in patients with SARS after intravenous use of exogenous corticosteroids, mostly located in medial condylus, lateral condylus and shaft of femur as well as in medial condylus or lateral condylus of tibia. So, MRI should

  5. High Efficiency of Human Normal Immunoglobulin for Intravenous Administration in a Patient with Kawasaki Syndrome Diagnosed in the Later Stages

    Directory of Open Access Journals (Sweden)

    Tatyana V. Sleptsova

    2016-01-01

    Full Text Available The article describes a case of late diagnosis of mucocutaneous lymphonodular syndrome (Kawasaki syndrome. At the beginning of the therapy, the child had fever, conjunctivitis, stomatitis, rash, solid swelling of hands and feet, and coronaritis with the development of aneurysms. The article describes the successful use of normal human immunoglobulin for intravenous administration at a dose of 2 g/kg body weight per course in combination with acetylsalicylic acid at the dose of 80 mg/kg per day. After 3 days of treatment, the rash disappeared; limb swelling and symptoms of conjunctivitis significantly reduced; and laboratory parameters of disease activity became normal (erythrocyte sedimentation rate, C-reactive protein concentration. After 3 months, inflammation in the coronary arteries was stopped. After 6 months, a regression of coronary artery aneurysms was recorded. No adverse effects during the immunoglobulin therapy were observed.

  6. Pharmacokinetics of flomoxef in mucosal tissue of the middle ear and mastoid following intravenous administration in humans.

    Science.gov (United States)

    Saito, H; Kimura, T; Takeda, T; Kishimoto, S; Oguma, T; Shimamura, K

    1990-01-01

    The pharmacokinetics of flomoxef in serum and in the mucosal tissue of the middle ear and mastoid were studied in 9 patients undergoing tympanoplasties. All patients received 1 g of flomoxef intravenously. Flomoxef levels in serum and in mucosal tissue were determined by a bioassay method. The peak value of mean concentrations of flomoxef in the mucosal tissue was 30.3 +/- 11.7 micrograms/ml at 10 min after the administrations. Pharmacokinetic analyses showed that the concentration of flomoxef in the mucosal tissue was over 1.56 micrograms/ml (which is the MIC90 for the common pathogens of otitis media) for more than 2 h and decreased parallel with serum concentration with a half-life of about 40 min.

  7. An overview of intravenous-related medication administration errors as reported to MEDMARX, a national medication error-reporting program.

    Science.gov (United States)

    Hicks, Rodney W; Becker, Shawn C

    2006-01-01

    Medication errors can be harmful, especially if they involve the intravenous (IV) route of administration. A mixed-methodology study using a 5-year review of 73,769 IV-related medication errors from a national medication error reporting program indicates that between 3% and 5% of these errors were harmful. The leading type of error was omission, and the leading cause of error involved clinician performance deficit. Using content analysis, three themes-product shortage, calculation errors, and tubing interconnectivity-emerge and appear to predispose patients to harm. Nurses often participate in IV therapy, and these findings have implications for practice and patient safety. Voluntary medication error-reporting programs afford an opportunity to improve patient care and to further understanding about the nature of IV-related medication errors.

  8. Pharmacokinetics of meloxicam following intravenous and oral administration in green iguanas (Iguana iguana).

    Science.gov (United States)

    Divers, Stephen J; Papich, Mark; McBride, Michael; Stedman, Nancy L; Perpinan, David; Koch, Thomas F; Hernandez, Sonia M; Barron, G Heather; Pethel, Melinda; Budsberg, Steven C

    2010-11-01

    To determine pharmacokinetics of meloxicam in healthy green iguanas following PO and IV administration and assess potential toxicity. 21 healthy green iguanas (Iguana iguana). To assess pharmacokinetics, 13 iguanas were administered a single dose (0.2 mg/kg) of meloxicam PO and, 14 days later, the same dose IV. To assess potential toxicity, 4 iguanas were given meloxicam at a dosage of 1 or 5 mg/kg, PO, every 24 hours for 12 days, and results of histologic examination were compared with results for another 4 iguanas given a single dose of meloxicam (0.2 mg/kg). There were no significant differences between PO and IV administration with regard to terminal half-life (mean ± SD, 12.96 ± 8.05 hours and 9.93 ± 4.92 hours, respectively), mean area under the curve to the last measured concentration (5.08 ± 1.62 μg•h/mL and 5.83 ± 2.49 μg•h/mL), volume of distribution (745 ± 475 mL/kg and 487 ± 266 mL/kg), or clearance (40.17 ± 10.35 mL/kg/h and 37.17 ± 16.08 mL/kg/h). Maximum plasma concentration was significantly greater following IV (0.63 ± 0.17 μg/mL) versus PO (0.19 ± 0.07 μg/mL) administration. Time from administration to maximum plasma concentration and mean residence time were significantly longer following PO versus IV administration. Daily administration of high doses (1 or 5 mg/kg) for 12 days did not induce any histologic changes in gastric, hepatic, or renal tissues. Results suggested that administration of meloxicam at a dose of 0.2 mg/kg IV or PO in green iguanas would result in plasma concentrations > 0.1 μg/mL for approximately 24 hours.

  9. Ocular disposition of treosulfan and its active epoxy-transformers following intravenous administration in rabbits.

    Science.gov (United States)

    Romański, Michał; Kasprzyk, Anna; Karbownik, Agnieszka; Główka, Franciszek K

    2016-10-01

    Treosulfan (TREO) has an established position in chemotherapy of advanced ovarian cancer but has been also applied in uveal melanoma patients. Moreover, it is used as an orphan drug for a myeloablative conditioning prior to stem cell transplantation. In this paper, biodistribution of prodrug TREO and its active monoepoxide (S,S-EBDM) and diepoxide (S,S-DEB) into aqueous humor of the eye was studied for the first time. For that purpose, alone TREO and the mixture of TREO, S,S-EBDM and S,S-DEB were administered intravenously to New Zealand White rabbits. The three analytes were determined in plasma and aqueous humor by validated HPLC methods and pharmacokinetic calculations were performed in WinNonlin. After the infusion of TREO, the aqueous humor/plasma C max ratio and area under the curve ratio amounted 0.04 and 0.10 for TREO, and 1.1 and 2.2 for S,S-EBDM, respectively. Following the bolus injection of the mixture of the prodrug and its epoxides, the aqueous humor/plasma C max ratios for TREO, S,S-EBDM and S,S-DEB were 0.05, 0.66, and 4.0, respectively. The presented results indicate a poor penetration of TREO into the eye, which may impair systemic treatment of ocular tumors but is beneficial in terms of a lack of clinically relevant ophthalmic adverse effects. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  10. Sedation and mechanical antinociception after intravenous administration of detomidine in donkeys: a dosage-effect study.

    Science.gov (United States)

    Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Varner, Kelley M; Robinson, Lauren S

    2015-02-21

    There is limited, useful, scientific information on detomidine in donkeys. This study compared the effects of intravenous saline, detomidine (10, 13.5, 17 and 20 μg/kg) and acepromazine (50 μg/kg) in donkeys by computing areas under the curve for 0-30, 30-60 and 60-120 minutes (AUC0-30, AUC30-60 and AUC60-120) for sedation scores, head heights and mechanical nociceptive thresholds (MNTs). For sedation scores, all detomidine treatments, except 10 μg/kg, increased AUC0-30 values compared with saline, and AUC0-30 values were larger for 17 μg/kg detomidine than for acepromazine. All head height AUC values were lower for detomidine than for saline (except AUC60-120 for 10 μg/kg detomidine) and acepromazine (except AUC0-30 for 10 and 20 μg/kg detomidine, and AUC60-120 for 10 μg/kg detomidine). For MNTs, all detomidine treatments increased AUC0-30 and AUC30-60 values compared with saline and acepromazine; AUC30-60 values were smaller for 10 μg/kg than for 17 and 20 μg/kg detomidine. MNT AUC60-120 values were larger for 20 μg/kg detomidine than for saline, 10 μg/kg detomidine and acepromazine. Detomidine induced sedation and antinociception, but only antinociception was dosage dependent. Selection of detomidine dosage for donkeys may depend on the required duration of sedation and/or degree of analgesia. British Veterinary Association.

  11. Pharmacokinetics of detomidine and its metabolites following intravenous and intramuscular administration in horses.

    Science.gov (United States)

    Grimsrud, K N; Mama, K R; Thomasy, S M; Stanley, S D

    2009-04-01

    Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. To describe the pharmacokinetics of detomidine and its metabolites, 3-hydroxy-detomidine (OH-detomidine) and detomidine 3-carboxylic acid (COOH-detomidine), after i.v. and i.m. administration of a single dose to horses. Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 microg/kg bwt and 4 a single dose i.m. 30 microg/kg bwt. In Phase 2, treatments were reversed. Plasma detomidine, OH-detomidine and COOH-detomidine were measured at predetermined time points using liquid chromatography-mass spectrometry. Following i.v. administration, detomidine was distributed rapidly and eliminated with a half-life (t1/2(el)) of approximately 30 min. Following i.m. administration, detomidine was distributed and eliminated with t1/2(el) of approximately one hour. Following, i.v. administration, detomidine clearance had a mean, median and range of 12.41, 11.66 and 10.10-18.37 ml/min/kg bwt, respectively. Detomidine had a volume of distribution with the mean, median and range for i.v. administration of 470, 478 and 215-687 ml/kg bwt, respectively. OH-detomidine was detected sooner than COOH-detomidine; however, COOH-detomidine had a much greater area under the curve. These pharmacokinetic parameters provide information necessary for determination of peak plasma concentrations and clearance of detomidine in mature horses. The results suggest that, when a longer duration of plasma concentration is warranted, the i.m. route should be considered.

  12. Factors Influencing ACT After Intravenous Bolus Administration of 100 IU/kg of Unfractionated Heparin During Cardiac Catheterization in Children.

    Science.gov (United States)

    Muster, Ileana; Haas, Thorsten; Quandt, Daniel; Kretschmar, Oliver; Knirsch, Walter

    2017-10-01

    Anticoagulation using intravenous bolus administration of unfractionated heparin (UFH) aims to prevent thromboembolic complications in children undergoing cardiac catheterization (CC). Optimal UFH dosage is needed to reduce bleeding complications. We analyzed the effect of bolus UFH on activated clotting time (ACT) in children undergoing CC focusing on age-dependent, anesthesia-related, or disease-related influencing factors. This retrospective single-center study of 183 pediatric patients receiving UFH during CC analyzed ACT measured at the end of CC. After bolus administration of 100 IU UFH/kg body weight, ACT values between 105 and 488 seconds were reached. Seventy-two percent were within target level of 160 to 240 seconds. Age-dependent differences were not obtained ( P = .407). The ACT values were lower due to hemodilution (total fluid and crystalloid administration during CC, both P ACT values but occurred more frequently in children between 1 month and 1 year of age (91%). In conclusion, with a bolus of 100 IU UFH/kg, an ACT target level of 160 to 240 seconds can be achieved during CC in children in 72%, which is influenced by hemodilution and anticoagulant and antiplatelet premedication but not by age.

  13. Preference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-positive early breast cancer (PrefHer)

    DEFF Research Database (Denmark)

    Pivot, Xavier; Gligorov, Joseph; Müller, Volkmar

    2013-01-01

    Subcutaneous trastuzumab has shown non-inferior efficacy and a similar pharmacokinetic and safety profile when compared with intravenous trastuzumab in patients with HER2-positive early breast cancer. We assessed patient preference for either subcutaneous or intravenous trastuzumab...

  14. Subcutaneous Administration of Tramadol after Elective Surgery Is as Effective as Intravenous Administration in Relieving Acute Pain and Inflammation in Dogs

    Science.gov (United States)

    Buhari, Salisu; Hashim, Kalthum; Yong Meng, Goh; Mustapha, Noordin Mohamed; Gan, Siew Hua

    2012-01-01

    Subcutaneous (SC) administration of tramadol was compared with intravenous (IV) administration to evaluate analgesia following canine ovariohysterectomy (OHE). Healthy female dogs (n = 12) between 1 and 3 years of age (1.95 ± 0.65 years), weighing between 10.5 and 17.1 kg (13.12 ± 1.95 kg), were used. Pain was assessed at baseline before surgery and then hourly for 8 hr after surgery. Tramadol was administered both SC and IV at a dose of 3 mg/kg and provided significant postoperative analgesia, as indicated by analgesiometry, β-endorphin levels, and interleukin 6 (IL-6) levels. The respiratory rates and rectal temperatures remained normal and were not significantly different between or within the groups. A significant increase in heart rate was observed at 4 hr for dogs in both groups relative to the baseline, but there was no significant difference in heart rates between the groups at any time point. A significant decrease in mechanical pain threshold was observed within each group after surgery, but both groups responded similarly, suggesting that SC administration of tramadol is as effective as IV administration. Increased serum levels of both IL-6 and β-endorphin 3 hr postoperatively further indicate that both routes of administration achieve similar pain control. Thus, the relative analgesic efficacy of SC tramadol is comparable to that of IV administration and can be used to achieve similar effects for postsurgical pain management in dogs undergoing OHE. PMID:22778699

  15. Errors in the administration of intravenous medications in patients undergoing anesthesia in the operating room

    Directory of Open Access Journals (Sweden)

    Juan David Miranda

    2013-03-01

    Full Text Available Errors in medication administration have affected the anesthetic practice over the time and have become a major cause of perioperative morbidity and mortality. Among different medical specialties, anesthesiology is perhaps the most likely to make mistakes in this procedure. This is because in many places around the world, a single professional "anesthesiologist" orders, prepares and administers a drug at one time and setting. For thirty years, Cooper disclosed the first reports of critical incidents and perioperative safety scheme, and in the 90s', Chopra performed a retrospective analysis, found that medication errors are the fourth most common that results in disability in 17% and death in 8%, these being preventable errors in 51% of cases. It’s essential for the safe practice of anesthesia to establish interventions for improving prevention programs, education, research and development, enabling break traditional paradigms, with the aim of making recommendations and standardize the safe administration of drugs in this field.

  16. 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

  17. Effect of intravenous administration of tramadol hydrochloride on the minimum alveolar concentration of isoflurane in rabbits.

    Science.gov (United States)

    Egger, Christine M; Souza, Marcy J; Greenacre, Cheryl B; Cox, Sherry K; Rohrbach, Barton W

    2009-08-01

    To evaluate the effect of IV administration of tramadol hydrochloride on the minimum alveolar concentration of isoflurane (ISOMAC) that prevented purposeful movement of rabbits in response to a noxious stimulus. Six 6- to 12-month-old female New Zealand White rabbits. Anesthesia was induced and maintained with isoflurane in oxygen. A baseline ISOMAC was determined by clamping a pedal digit with sponge forceps until gross purposeful movement was detected or a period of 60 seconds elapsed. Subsequently, tramadol (4.4 mg/kg) was administered IV and the posttreatment ISOMAC (ISOMAC(T)) was measured. Mean +/- SD ISOMAC and ISOMAC(T) values were 2.33 +/- 0.13% and 2.12 +/- 0.17%, respectively. The ISOMAC value decreased by 9 +/- 4% after tramadol was administered. Plasma tramadol and its major metabolite (M1) concentrations at the time of ISOMAC(T) determination varied widely (ranges, 181 to 636 ng/mL and 32 to 61 ng/mL, respectively). Intervals to determination of ISOMAC(T) and plasma tramadol and M1 concentrations were not correlated with percentage change in the ISOMAC. Heart rate decreased significantly immediately after tramadol administration but by 10 minutes afterward was not different from the pretreatment value. Systolic arterial blood pressure decreased to approximately 60 mm Hg for approximately 5 minutes in 3 rabbits after tramadol administration. No adverse effects were detected. As administered, tramadol had a significant but clinically unimportant effect on the ISOMAC in rabbits. Higher doses of tramadol may provide clinically important reductions but may result in a greater degree of cardiovascular depression.

  18. Effect of continuous intravenous administration of a 50% dextrose solution on phosphorus homeostasis in dairy cows.

    Science.gov (United States)

    Grünberg, Walter; Morin, Dawn E; Drackley, James K; Barger, Anne M; Constable, Peter D

    2006-08-01

    To determine the effect of continuous IV administration of 50% dextrose solution on phosphorus homeostasis in lactating dairy cows. Clinical trial. 4 multiparous Jersey cows. Cows were administered 50% dextrose solution IV (0.3 g/kg/h [0.14 g/lb/h]) for 5 days. Plasma concentrations of glucose, immune-reactive insulin (IRI), and phosphorus were determined before, during, and for 72 hours after dextrose infusion. Phosphorus intake and losses of phosphorus in urine, feces, and milk were determined. Each cow received a sham treatment that included instrumentation and sampling but not administration of dextrose. Plasma glucose, IRI, and phosphorus concentrations were stable during sham treatment. Plasma phosphorus concentration decreased rapidly after onset of dextrose infusion, reaching a nadir in 24 hours and remaining less than baseline value for 36 hours. Plasma phosphorus concentration increased after dextrose infusion was stopped, peaking in 6 hours. Urinary phosphorus excretion did not change during dextrose infusion, but phosphorus intake decreased because of reduced feed intake, followed by decreased fecal phosphorus loss and milk yield. Rapid changes in plasma phosphorus concentration at the start and end of dextrose infusion were temporally associated with changes in plasma glucose and IRI concentrations and most likely caused by compartmental shifts of phosphorus. Hypophosphatemia developed in response to hyperglycemia or hyperinsulinemia in dairy cows administered dextrose via continuous IV infusion. Veterinarians should monitor plasma phosphorus concentration when administering dextrose in this manner, particularly in cows with decreased appetite or preexisting hypophosphatemia.

  19. Intravenous dextrose administration reduces postoperative antiemetic rescue treatment requirements and postanesthesia care unit length of stay.

    Science.gov (United States)

    Dabu-Bondoc, Susan; Vadivelu, Nalini; Shimono, Chantelle; English, Annette; Kosarussavadi, Boonsri; Dai, Feng; Shelley, Kirk; Feinleib, Jessica

    2013-09-01

    Postoperative nausea and vomiting (PONV) remains the most common postoperative complication, and causes decreased patient satisfaction, prolonged postoperative hospital stays, and unanticipated admission. There are limited data that indicate that dextrose may reduce nausea and vomiting. In this trial, we attempted to determine whether the rate of PONV can be decreased by postoperative administration of IV dextrose bolus. To test the effect of postoperative dextrose administration on PONV rates, we conducted a double-blind, randomized, placebo-controlled trial. We enrolled 62 nondiabetic, ASA class I or II nonsmoking outpatients scheduled for gynecologic laparoscopic and hysteroscopic procedures. Patients were randomized into 2 groups: the treatment group received dextrose 5% in Ringer lactate solution, and the control (placebo) group received Ringer lactate solution given immediately after surgery. All patients underwent a standardized general anesthesia and received 1 dose of antiemetic a half hour before emergence from anesthesia. PONV scores, antiemetic rescue medications, narcotic consumption, and discharge time were recorded in the postanesthesia care unit (PACU) in half-hour intervals. The 2 groups were similar with regard to age, weight, anxiety scores, prior PONV, non per os status, presurgical glucose, anesthetic duration, intraoperative narcotic use, and total weight-based fluid volume received. Postoperative nausea scores were not significantly different in the dextrose group compared with the control group (P > 0.05) after Bonferroni correction for repeated measurements over time. However, patients who received dextrose 5% in Ringer lactate solution consumed less rescue antiemetic medications (ratio mean difference, 0.56; 95% confidence interval, 0.39-0.82; P = 0.02), and had a shorter length of stay in the PACU (ratio mean difference, 0.80; 95% confidence interval, 0.66-0.97; P = 0.03) compared with patients in the control group. In this trial

  20. Complement activation-related pseudoallergy in dogs following intravenous administration of a liposomal formulation of meglumine antimoniate

    Directory of Open Access Journals (Sweden)

    Raul R. Ribeiro

    2013-08-01

    Full Text Available The increasing use of nanotechnologies in advanced therapies has allowed the observation of specific adverse reactions related to nanostructures. The toxicity of a novel liposome formulation of meglumine antimoniate in dogs with visceral leishmaniasis after single dose has been investigated. Groups of 12 animals received by the intravenous route a single dose of liposomal meglumine antimoniate (group I [GI], 6.5 mg Sb/kg, empty liposomes (GII or isotonic saline (GIII. Evaluation of hematological and biochemical parameters showed no significant changes 4 days after administration. No undesired effects were registered in the GIII. However, adverse reactions were observed in 67.7% of dogs from both groups that received liposomal formulations. The side effects began moments after bolus administration and disappeared during the first 15 minutes after treatment. Prostation, sialorrhea and defecation were the most frequent clinical signs, registered in 33.3% and 41.6 % of animals from the groups GI and GII, respectively. Tachypnea, mydriasis, miosis, vomiting and cyanosis were also registered in both groups. The adverse reactions observed in this study were attributed to the activation of the complement system by lipid vesicles in a phenomenon known as Complement Activation-Related Pseudoallergy (CARPA. The influence of the physical-chemical characteristics of liposomal formulation in the triggering of CARPA is discussed.

  1. 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.

  2. Respiratory depression after intravenous administration of delta-selective opioid peptide analogs.

    Science.gov (United States)

    Szeto, H H; Soong, Y; Wu, D; Olariu, N; Kett, A; Kim, H; Clapp, J F

    1999-01-01

    We compared the effects of three micro-(DAMGO, DALDA, TNPO) and three delta-(DPDPE, DELT, SNC-80) opioid agonists on arterial blood gas after IV administration in awake sheep. None of the mu agonists altered pO2, pCO2 or pH. All three mu agonists decreased pO2 increased pCO2 and decreased pO2, and this effect was not sensitive to naloxone or TIPPpsi, a delta-antagonist, suggesting that it is not mediated by beta-opioid receptors. When administered to pregnant animals, there were significant changes in fetal pCO2 and pH. It may be possible to develop delta-selective opioid agonists which do not produce respiratory depression.

  3. Efficacy, safety and anticancer activity of protein nanoparticle-based delivery of doxorubicin through intravenous administration in rats.

    Directory of Open Access Journals (Sweden)

    Kishore Golla

    Full Text Available Doxorubicin is a potent anticancer drug and a major limiting factor that hinders therapeutic use as its high levels of systemic circulation often associated with various off-target effects, particularly cardiotoxicity. The present study focuses on evaluation of the efficacy of doxorubicin when it is loaded into the protein nanoparticles and delivered intravenously in rats bearing Hepatocellular carcinoma (HCC. The proteins selected as carrier were Apotransferrin and Lactoferrin, since the receptors for these two proteins are known to be over expressed on cancer cells due to their iron transport capacity.Doxorubicin loaded apotransferrin (Apodoxonano and lactoferrin nanoparticles (Lactodoxonano were prepared by sol-oil chemistry. HCC in the rats was induced by 100 mg/l of diethylnitrosamine (DENA in drinking water for 8 weeks. Rats received 5 doses of 2 mg/kg drug equivalent nanoparticles through intravenous administration. Pharmacokinetics and toxicity of nanoformulations was evaluated in healthy rats and anticancer activity was studied in DENA treated rats. The anticancer activity was evaluated through counting of the liver nodules, H & E analysis and by estimating the expression levels of angiogenic and antitumor markers.In rats treated with nanoformulations, the numbers of liver nodules were found to be significantly reduced. They showed highest drug accumulation in liver (22.4 and 19.5 µg/g. Both nanoformulations showed higher localization compared to doxorubicin (Doxo when delivered in the absence of a carrier. Higher amounts of Doxo (195 µg/g were removed through kidney, while Apodoxonano and Lactodoxonano showed only a minimal amount of removal (<40 µg/g, suggesting the extended bioavailability of Doxo when delivered through nanoformulation. Safety analysis shows minimal cardiotoxicity due to lower drug accumulation in heart in the case of nanoformulation.Drug delivery through nanoformulations not only minimizes the cardiotoxicity of

  4. Effect of intravenous administration of dextrose on coagulation in healthy dogs.

    Science.gov (United States)

    Gonzales, Jennifer L; Hanel, Rita M; Hansen, Bernie D; Marks, Steve L

    2011-04-01

    To investigate effects of IV administration of dextrose on coagulation in healthy dogs. 7 dogs. Thromboelastography and coagulation panel analysis were used to assess coagulation. Samples (S1 through S9) were collected during the study phases: phase 0 (S1 [baseline]); phase 1 (S2 and S3), infusion of crystalloid fluid without dextrose; phase 2 (S4 and S5), high-rate dextrose infusion; phase 3 (S6, S7, and S8), moderate-rate dextrose infusion; and phase 4 (S9), discontinuation of fluids for 24 hours. In phase 3, dogs were allocated to 2 groups; 1 was administered dextrose at a rate comparable to total parental nutrition (40% of resting energy requirement; group A), and 1 was administered dextrose at rates equaling 70% to 90% of resting energy requirement (group B). Blood glucose concentration was measured every 2 hours. No dogs had clinically relevant sustained hyperglycemia. Maximum amplitude and elastic shear modulus were significantly lower at S6 than at S1 through S4. Concentration of D-dimer was significantly higher at S6 than at S1, S3, and S4 and significantly higher at S5 than at S3. Prothrombin time was significantly prolonged at S3, S5, S7, S8, and S9, compared with the value at S1. Activated partial thromboplastin time was significantly prolonged at S5 and S6, compared with values at S1, S2, S3, S4, and S9. IV administration of dextrose to healthy dogs at rates comparable to or higher than those for conventional parenteral nutrition resulted in mild but clinically unimportant interference with coagulation.

  5. Uptake of iodinated deoxyuridine in a murine melonama following multiple-day intravenous infusions

    International Nuclear Information System (INIS)

    Laster, B.H.; Popenoe, E.; Commerford, S.L.; Matsui, K.; Coderre, J.; Fand, I.; Fairchild, R.

    1985-01-01

    Techniques are described for multi-day intravenous (i.v.) infusions of iodinated deoxyuridine (IdUrd) into mice. Percent incorporation into DNA as a thymidine (Thd) analog is reported, as measured by radioactive tag ( 125 IdUrd) and by neutron activation analysis (NAA). Quantitative measurements of IdUrd incorporation in DNA are requisite for meaningful evaluation of the effects of radiation enhancement resulting from radiation sensitization and the stimulation of Auger cascades (photon activation)

  6. Pharmacokinetics and metabolism of cyadox and its main metabolites in beagle dogs following oral, intramuscular and intravenous administration

    Directory of Open Access Journals (Sweden)

    Adeel Sattar

    2016-08-01

    Full Text Available Cyadox (Cyx is an antibacterial drug of the quinoxaline group that exerts markedly lower toxicity in animals, compared to its congeners. Here, the pharmacokinetics and metabolism of Cyx after oral (PO, intramuscular (IM and intravenous (IV routes of administration were studied to establish safety criteria for the clinical use of Cyx in animals. Six beagle dogs (3 males, 3 females were administered Cyx through PO (40 mg kg-1 b.w., IM (10 mg kg-1 b.w. and IV (10 mg kg-1 b.w. routes with a washout period of 2 weeks in a crossover design. Highly sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV was employed for determination of Cyx and its main metabolites, 1, 4-bisdesoxycyadox (Cy1, cyadox-1-monoxide (Cy2, N-(quinoxaline-2-methyl-cyanide acetyl hydrazine (Cy4 and quinoxaline-2-carboxylic acid (Cy6 in plasma, urine and feces of dogs. The oral bioavailability of Cyx was 4.75%, suggesting first-pass effect in dogs. The concentration vs. time profile in plasma after PO administration indicates that Cyx is rapidly dissociated into its metabolites and eliminated from plasma earlier, compared to its metabolites. The areas under the curve (AUC of Cyx after PO, IM and IV administration were 1.22 h×µg mL-1, 6.3 h×µg mL-1, and 6.66 h×µg mL-1, while mean resident times (MRT were 7.32, 3.58 and 0.556 h, respectively. Total recovery of Cyx and its metabolites was >60% with each administration route. In feces, 48.83% drug was recovered after PO administration, while 18.15% and 17.11% after IM and IV injections, respectively, suggesting renal clearance as the major route of excretion with IM and IV administration and feces as the major route with PO delivery. Our comprehensive evaluation of Cyx has uncovered detailed information that should facilitate its judicious use in animals by improving understanding of its pharmacology.

  7. Intravenous maternal -arginine administration to twin-bearing ewes during late pregnancy enhances placental growth and development.

    Science.gov (United States)

    van der Linden, D S; Sciascia, Q; Sales, F; Wards, N J; Oliver, M H; McCoard, S A

    2015-10-01

    This study aimed to investigate if intravenous maternal Arg administration to well-fed twin-bearing ewes, from 100 to 140 d of gestation or birth, could enhance placental development and placental nutrient transport. Ewes received intravenous infusions of saline (control) or 345 μmol Arg HCl/kg of BW 3 times daily from d 100 of pregnancy (P100) to d 140 of pregnancy (P140; cohort 1) or from P100 to birth (cohort 2). At P140, ewes in cohort 1 were euthanized and individual placentae per fetus were dissected and placentomes were classed per type (A to D) and size (light to heavy). Placentome number and individual weight were recorded. As an indicator of placental nutrient transport, blood plasma was collected from the uterine ovarian vein (UOV), uterine artery (UA), and umbilical vein and artery at the time of euthanasia and analyzed for metabolites and free AA concentrations. The ewes in cohort 2 were allowed to lamb and lambs were weighed at birth. The expelled placenta was dissected and number of cotyledons and weights of total cotyledons, remaining fetal membranes, and total placenta were recorded. At P140, Arg-infused ewes had a 63% ( = 0.03) greater number of unoccupied caruncles than control ewes. No differences were observed for placental weight at P140. At birth, lambs from Arg-infused ewes tended to have 11% ( = 0.09) greater placental weight and 34% ( = 0.03) greater total cotyledon weight compared with control lambs. Arginine-infused ewes (Arg-infused) had increased concentrations of Arg ( = 0.0001) and ornithine (Orn; = 0.004) but decreased concentrations of Met ( = 0.01) and His ( = 0.02 and = 0.09, respectively) compared with control ewes in plasma UOV and UA. Fetuses from Arg-infused ewes had increased concentrations of Orn ( = 0.005) and decreased concentrations of His ( = 0.006), Met ( = 0.003), and Lys ( = 0.01) but no differences in Arg ( > 0.10) concentrations were found compared with control fetuses in umbilical artery and vein plasma. This

  8. The effect of giving detailed information about intravenous radiopharmaceutical administration on the anxiety level of patients who request more information

    International Nuclear Information System (INIS)

    Kaya, E.; Ciftci, I.; Demirel, R.; Gecici, O.; Cigerci, Y.

    2010-01-01

    Nuclear medicine procedures use radiopharmaceuticals, which produce radiation and potential adverse reactions, albeit at a low rate. It is the patient's ethical, legal, and medical right to be informed of the potential side effects of procedures applied to them. Our purpose was to determine the effect of providing information about intravenous radiopharmaceutical administration on the anxiety level of patients who request more information. This study was completed in two separate Nuclear Medicine Departments. The study included 620 (247 M, 373 F) patients who had been referred for myocardial perfusion, bone, dynamic renal, and thyroid scintigraphic examinations. The patients were divided into two groups according to whether they requested more information or not. Group 1 consisted of 388 patients who wanted to receive more information about the procedure, while Group 2 consisted of 232 patients who did not request additional information. The State-Trait Anxiety Inventory (STAI-S and STAI-T) was used to determine a patient's anxiety level. After simple information was given, state and trait anxiety levels were measured in both groups. We gave detailed information to the patients in Group 1 and then measured state anxiety again. Detailed information included an explanation of the radiopharmaceutical risk and probable side effects due to the scan procedure. There was no statistical difference between Groups 1 and 2 in STAI-T or STAI-S scores after simple information was given (p=0.741 and p=0.945, respectively). The mean value of STAI-S score was increased after the provision of detailed information and there was a statistically significant difference between after simple information STAI-S and after detailed information STAI-S (p<0.001). The STAI-S score was increased in 246 patients and decreased in 110 patients after detailed information, while there was no change in 32 patients. After detailed information, the greatest increase in STAI-S score was seen in the

  9. Topical versus intravenous administration of tranexamic acid in primary total hip arthroplasty: a systematic review and meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Sammy A. Hanna

    2016-09-01

    Full Text Available Tranexamic acid (TA is widely used by orthopedic surgeons to decrease blood loss and the need for transfusion following total hip arthroplasty (THA. Although both intravenous and topical applications are described in the literature, there remains no consensus regarding the optimal regimen, dosage and method of delivery of TA during THA. In addition, concerns still exist regarding the risk of thromboembolic events with intravenous administration. The purpose of this meta-analysis was to compare the efficacy and safety of topical versus intravenous administration of TA in THA. A systemic review of the electronic databases PubMed, CENTRAL, EMBASE and Google Scholar was undertaken to identify all randomized controlled trials (RCTs comparing the topical and intravenous administration of TA during THA, in terms of total blood loss, rate of blood transfusion and incidence of deep venous thrombosis (DVT and pulmonary embolism (PE post-operatively. A meta-analysis was performed to evaluate and compare the efficacy and safety of both methods of administration. Of 248 potentially relevant papers, three RCTs comprising (482 were eligible for data extraction and metaanalysis. The results showed a slightly higher amount of blood loss [Mean Difference (MD – 46.37, P=0.12, 95% confidence interval (CI – 12.54 to 105.29] and rate of transfusion (Risk Ratio 1.30, P=0.39, 95%CI 0.71 to 2.37 postoperatively in the topical TA group, but both did not reach statistical significance. There were 3 cases (1.2% of DVT/PE in the intravenous group and one case (0.4% in the topical group. Topical TA is an effective and safe method to reduce blood loss and the rate of transfusion following primary THA. It has comparative effectiveness to IV administration with slightly less post-operative thromboembolic complications. Larger and better-designed RCTs are required to establish the optimum dosage and regimen for topical use.

  10. Comparative pharmacokinetics of enrofloxacin, danofloxacin, and marbofloxacin after intravenous and oral administration in Japanese quail (Coturnix coturnix japonica).

    Science.gov (United States)

    Haritova, Aneliya; Dimitrova, Dimitrichka; Dinev, Toncho; Moutafchieva, Rumyana; Lashev, Lubomir

    2013-03-01

    A population approach was used to evaluate the pharmacokinetic parameters of 3 fluoroquinolones administered to Japanese quail (Coturnix coturnix japonica). Healthy adult quail (n = 50) were divided into 3 groups, each administered a separate intravenous and oral dose of the compounded drug: enrofloxacin at 10 mg/kg (n = 18; 9 male, 9 female), danofloxacin at 10 mg/kg (n = 12; 6 male, 6 female), and marbofloxacin at 5 mg/kg (n = 20; 10 male, 10 female). A fourth group was used as a control (n = 5). Enrofloxacin was metabolized extensively to ciprofloxacin, while no metabolites of either danofloxacin or marbofloxacin were detected. The volume of distribution was high, greater than 1 in all cases, and highest for danofloxacin, followed by enrofloxacin, then marbofloxacin. The total body clearance was higher in quail than that reported for other avian species with the exception of ostriches. As in mammals, the lowest clearance rate of the 3 fluoroquinolones was observed for marbofloxacin. Enrofloxacin was absorbed most rapidly, followed by marbofloxacin, then danofloxacin. The highest bioavailability was observed for danofloxacin followed by marbofloxacin, while very low bioavailability with significant conversion to ciprofloxacin was observed for enrofloxacin. Population analysis showed low intersubject variability for danofloxacin and marbofloxacin in contrast to that for enrofloxacin and its main metabolite, ciprofloxacin. Because of their more favorable pharmacokinetic properties after oral administration, either danofloxacin or marbofloxacin appears to be preferable to enrofloxacin for the treatment of susceptible bacterial infection in Japanese quail.

  11. 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

  12. Daily rhythms in blood and milk lead toxicokinetics following intravenous administration of lead acetate to dairy cows in summer

    Science.gov (United States)

    Valtorta, S. E.; Scaglione, M. C.; Acosta, P.; Coronel, J. E.; Beldomenico, H. R.; Boggio, J. C.

    2006-01-01

    The objective of this study was to investigate circadian variations of blood and milk lead toxicokinetics in dairy cows in summer. Twenty lactating Holstein animals were randomly assigned to four treatments corresponding to different hours after onset of light (HALO): 2, 8, 14, and 20. Cows received a single intravenous administration of 2.5 mg/kg lead as lead acetate. Blood and milk samples were taken and analyzed by atomic absorption spectrophotometry. For each toxicokinetic parameter, a one-way analysis of variance (ANOVA) was performed to outline the existence of daily variations. Significant blood differences as a function of HALO were found for the hybrid constant of distribution (α), hybrid constant of elimination (β), elimination half-life ({text{t}}_{{{text{1/2 β }}}} ), area under the curve (AUC), volume of distribution at steady state (Vss) and clearance (ClB) ( pMilk data showed significant differences for maximum concentration and AUC ( pmilk. It differed significantly throughout the day ( pMilk data for the significant parameters could be fitted to circadian rhythms. No circadian rhythms were detected in blood parameters or in the ratio AUCmilk/AUCblood.

  13. Intravenous fluid administration may improve post-operative course of patients with chronic subdural hematoma: a retrospective study.

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    Miroslaw Janowski

    Full Text Available BACKGROUND: The treatment of chronic subdural hematoma (cSDH is still charged of significant risk of hematoma recurrence. Patient-related predictors and the surgical procedures themselves have been addressed in many studies. In contrast, postoperative management has infrequently been subjected to detailed analysis. Moreover variable intravenous fluid administration (IFA was not reported in literature till now in the context of cSDH treatment. METHODOLOGY/PRINCIPAL FINDINGS: A total of 45 patients with cSDH were operated in our department via two burr hole craniostomy within one calendar year. Downward drainage was routinely left in hematoma cavity for a one day. Independent variables selected for the analysis were related to various aspects of patient management, including IFA. Two dependent variables were chosen as measure of clinical course: the rate of hematoma recurrence (RHR and neurological status at discharge from hospital expressed in points of Glasgow Outcome Scale (GOS. Univariate and multivariate regression analyses were performed. Hematoma recurrence with subsequent evacuation occurred in 7 (15% patients. Univariate regression analysis revealed that length of IFA after surgery influenced both dependent variables: RHR (p = 0.045 and GOS (p = 0.023. Multivariate regression performed by backward elimination method confirmed that IFA is a sole independent factor influencing RHR. Post hoc dichotomous division of patients revealed that those receiving at least 2000 ml/day over 3 day period revealed lower RHR than the group with less intensive IFA. (p = 0.031. CONCLUSIONS/SIGNIFICANCE: IFA has been found to be a sole factor influencing both: RHR and GOS. Based on those results we may recommend administration of at least 2000 ml per 3 days post-operatively to decrease the risk of hematoma recurrence.

  14. Comparison of topical and intravenous administration of tranexamic acid for blood loss control during total joint replacement: Review of literature

    Directory of Open Access Journals (Sweden)

    Georgi P. Georgiev

    2018-04-01

    Full Text Available Purpose: Many randomised controlled trials and meta-analysis studies have presented the efficacy of tranexamic acid (TXA without an increase of complications. However, questions still remain about the type of administration, optimal dose and secondary outcomes of TXA in total hip arthroplasty and total knee arthroplasty. The aim of this review is to summarise the existing information in literature concerning the pharmacological characteristics of TXA, forms, doses, types of application and contraindications for its use. Methods: A literature review containing 63 articles from the PubMed data starting from the first description of tranexamic acid until now was made in trying to present the existing information in a simple and effective way. Results: TXA leads to statistically significant reduction of peri and postoperative bleeding and in that way decreases blood transfusion rates and the infection risk. Topical and intravenous (IV use of TXA revealed similar results, with no increase of deep venous thrombosis. Therefore, topical TXA could be a reasonable alternative in patients with contraindications for IV application of TXA. Conclusions: Blood loss control with TXA, a synthetic analogue of the amino acid lysine, may be an excellent and safe alternative to allogeneic blood transfusion after total hip arthroplasty and total knee arthroplasty. Further studies are needed to establish the efficacy of combined IV and topical administration of TXA with regard to diminishing blood loss and reducing hospital stay. The Translational Potential of this Article: This review briefly presents the pharmacological characteristics of TXA, forms, doses, types of application and contraindications for its use with regard to diminishing blood loss and reducing hospital stay for better therapeutic strategies in orthopaedics. Keywords: Arthroplasty, Review, Tranexamic acid

  15. Effects of a selective cannabinoid CB2 agonist and antagonist on intravenous nicotine self administration and reinstatement of nicotine seeking.

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    Islam Gamaleddin

    Full Text Available Over the last decade there have been significant advances in the discovery and understanding of the cannabinoid system along with the development of pharmacologic tools that modulate its function. Characterization of the crosstalk between nicotine addiction and the cannabinoid system may have significant implications on our understanding of the neurobiological mechanisms underlying nicotine dependence. Two types of cannabinoid receptors (CB1 and CB2 have been identified. CB1 receptors are expressed in the brain and modulate drug taking and drug seeking for various drugs of abuse, including nicotine. CB2 receptors have been recently identified in the brain and have been proposed to play a functional role in mental disorders and drug addiction. Our objective was to explore the role of CB2 receptors on intravenous nicotine self administration under two schedules of reinforcement (fixed and progressive ratio and on nicotine seeking induced by nicotine priming or by nicotine associated cues. For this, we evaluated the effects of various doses of the selective CB2 antagonist AM630 (1.25 to 5 mg/kg and CB2 agonist AM1241 (1 to 10 mg/kg on these behavioral responses in rats. Different groups of male Long Evans rats were trained to lever press for nicotine at a unit dose of 30 µg/kg/infusion. Subsequently, animals were randomized using a Latin-square design and injected with either AM1241 or AM630 using a counterbalanced within subject design. Administration of the CB2 ligands did not affect either nicotine-taking nicotine-seeking behavior. Our results do not support the involvement of CB2 receptors in nicotine-taking or nicotine-seeking behavior.

  16. Safety studies on intravenous administration of oncolytic recombinant vesicular stomatitis virus in purpose-bred beagle dogs.

    Science.gov (United States)

    LeBlanc, Amy K; Naik, Shruthi; Galyon, Gina D; Jenks, Nathan; Steele, Mike; Peng, Kah-Whye; Federspiel, Mark J; Donnell, Robert; Russell, Stephen J

    2013-12-01

    VSV-IFNβ-NIS is a novel recombinant oncolytic vesicular stomatitis virus (VSV) with documented efficacy and safety in preclinical murine models of cancer. To facilitate clinical translation of this promising oncolytic therapy in patients with disseminated cancer, we are utilizing a comparative oncology approach to gather data describing the safety and efficacy of systemic VSV-IFNβ-NIS administration in dogs with naturally occurring cancer. In support of this, we executed a dose-escalation study in purpose-bred dogs to determine the maximum tolerated dose (MTD) of systemic VSV-hIFNβ-NIS, characterize the adverse event profile, and describe routes and duration of viral shedding in healthy, immune-competent dogs. The data indicate that an intravenous dose of 10(10) TCID50 is well tolerated in dogs. Expected adverse events were mild to moderate fever, self-limiting nausea and vomiting, lymphopenia, and oral mucosal lesions. Unexpected adverse events included prolongation of partial thromboplastin time, development of bacterial urinary tract infection, and scrotal dermatitis, and in one dog receiving 10(11) TCID50 (10 × the MTD), the development of severe hepatotoxicity and symptoms of shock leading to euthanasia. Viral shedding data indicate that detectable viral genome in blood diminishes rapidly with anti-VSV neutralizing antibodies detectable in blood as early as day 5 postintravenous virus administration. While low levels of viral genome copies were detectable in plasma, urine, and buccal swabs of dogs treated at the MTD, no infectious virus was detectable in plasma, urine, or buccal swabs at any of the doses tested. These studies confirm that VSV can be safely administered systemically in dogs, justifying the use of oncolytic VSV as a novel therapy for the treatment of canine cancer.

  17. Intraarticular and intravenous administration of 99MTc-HMPAO-labeled human mesenchymal stem cells (99MTC-AH-MSCS): In vivo imaging and biodistribution

    International Nuclear Information System (INIS)

    Meseguer-Olmo, Luis; Montellano, Antonio Jesús; Martínez, Teresa; Martínez, Carlos M.; Revilla-Nuin, Beatriz; Roldán, Marta; Mora, Cristina Fuente; López-Lucas, Maria Dolores; Fuente, Teodomiro

    2017-01-01

    Introduction: Therapeutic application of intravenous administered (IV) human bone marrow-derived mesenchymal stem cells (ahMSCs) appears to have as main drawback the massive retention of cells in the lung parenchyma, questioning the suitability of this via of administration. Intraarticular administration (IAR) could be considered as an alternative route for therapy in degenerative and traumatic joint lesions. Our work is outlined as a comparative study of biodistribution of 99m Tc-ahMSCs after IV and IAR administration, via scintigraphic study in an animal model. Methods: Isolated primary culture of adult human mesenchymal stem cells was labeled with 99m Tc-HMPAO for scintigraphic study of in vivo distribution after intravenous and intra-articular (knee) administration in rabbits. Results: IV administration of radiolabeled ahMSCs showed the bulk of radioactivity in the lung parenchyma while IAR images showed activity mainly in the injected cavity and complete absence of uptake in pulmonary bed. Conclusions: Our study shows that IAR administration overcomes the limitations of IV injection, in particular, those related to cells destruction in the lung parenchyma. After IAR administration, cells remain within the joint cavity, as expected given its size and adhesion properties. Advances in knowledge: Intra-articular administration of adult human mesenchymal stem cells could be a suitable route for therapeutic effect in joint lesions. Implications for patient care: Local administration of adult human mesenchymal stem cells could improve their therapeutic effects, minimizing side effects in patients.

  18. 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.

  19. Histopathological confirmation of similar intramucosal distribution of fluorescein in both intravenous administration and local mucosal application for probe-based confocal laser endomicroscopy of the normal stomach.

    Science.gov (United States)

    Nonaka, Kouichi; Ohata, Ken; Ban, Shinichi; Ichihara, Shin; Takasugi, Rumi; Minato, Yohei; Tashima, Tomoaki; Matsuyama, Yasushi; Takita, Maiko; Matsuhashi, Nobuyuki; Neumann, Helmut

    2015-12-16

    Probe-based confocal laser endomicroscopy (pCLE) is capable of acquiring in vivo magnified cross-section images of the gastric mucosa. Intravenous injection of fluorescein sodium is used for confocal imaging. However, it is still under debate if local administration of the dye to the mucosa is also effective for confocal imaging as it is not yet clear if topical application also reveals the intramucosal distribution of fluorescein. The objective of this study was to evaluate the intramucosal distribution of fluorescein sodium after topical application and to compare the distribution to the conventional intravenous injection used for confocal imaging. pCLE of the stomach uninfected with Helicobacter pylori was performed in a healthy male employing intravenous administration and local mucosal application of fluorescein. The mucosa of the lower gastric body was biopsied 1 min and 5 min after intravenous administration or local mucosal application of fluorescein, and the distribution of fluorescein in the biopsy samples was examined histologically. Green fluorescence was already observed in the cytoplasm of fundic glandular cells in the biopsied deep mucosa 1 min after local mucosal application of fluorescein. It was also observed in the foveolar lumen and inter-foveolar lamina propria, although it was noted at only a few sites. In the tissue biopsied 5 min after the local mucosal application of fluorescein, green fluorescence was more frequently noted in the cytoplasm of fundic glandular cells than in that 1 min after the local mucosal application of fluorescein, although obvious green fluorescence was not identified in the foveolar lumen or inter-foveolar lamina propria. The distribution of intravenously administered fluorescein in the cytoplasm of fundic glandular cells was also clearly observed similarly to that after local mucosal application of fluorescein. Green fluorescence in more cells was observed in many cells 5 min after intravenous administration compared

  20. Association of systolic blood pressure drop with intravenous administration of itraconazole in children with hemato-oncologic disease

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    Lee HJ

    2015-12-01

    Full Text Available Hyeong Jin Lee,1,* Bongjin Lee,2,* June Dong Park,2 Hyung Joo Jeong,2 Yu Hyeon Choi,2 Hee Young Ju,1 Che Ry Hong,1 Ji Won Lee,1 Hyery Kim,1 Dong In Suh,3 Kyung Duk Park,1 Hyoung Jin Kang,1 Hee Young Shin,1 Hyo Seop Ahn1 1Department of Pediatrics, Cancer Research Institute, 2Division of Pediatric Intensive Care, Department of Pediatrics, 3Division of Pulmonology, Department of Pediatrics, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea *These authors contributed equally to this work Purpose: Although few adverse effects have been reported for itraconazole, a widely used antifungal therapy for febrile neutropenia, we found intravenous (IV itraconazole to be associated with serious cases of blood pressure (BP drop. We therefore evaluated the incidence and risk factors for BP drop during IV administration of the drug.Materials and methods: We reviewed the medical records of children with hemato-oncologic disease who were treated with IV itraconazole from January 2012 to December 2013. By analyzing systolic BP (SBP measurements made from 4 hours before through to 4 hours after itraconazole administration, we evaluated the changes in SBP and the risk factors for an SBP drop, especially clinically meaningful (≥20% drops.Results: Itraconazole was administered 2,627 times to 180 patients. The SBP during the 4 hours following itraconazole administration was lower than during the 4 hours before administration (104 [53.0–160.33 mmHg] versus 105 [59.8–148.3 mmHg]; P<0.001. The decrease in SBP was associated with the application of continuous renal replacement therapy (CRRT (P=0.012 and the use of inotropic (P=0.005 and hypotensive drugs (P=0.021. A clinically meaningful SBP drop was seen in 5.37% (141 out of 2,627 of the administrations, and the use of inotropics (odds ratio [OR] 6.70, 95% confidence interval [CI] 3.22–13.92; P<0.001, reducing the dose of inotropics (OR 8.08; 95% CI 1.39–46.94; P=0

  1. Prevalence of NSF following intravenous gadolinium-contrast media administration in dialysis patients with endstage renal disease

    Energy Technology Data Exchange (ETDEWEB)

    Heinz-Peer, Gertraud, E-mail: gertraud.heinz@meduniwien.ac.a [Department of Radiology, Medical University of Vienna (Austria); Neruda, Anita [Department of Radiology, Medical University of Vienna (Austria); Watschinger, Bruno; Vychytil, Andreas [Department of Nephrology, Medical University of Vienna (Austria); Geusau, Alexandra [Department of Dermatology, Medical University of Vienna (Austria); Haumer, Markus [Department of Internal Medicine II, Medical University of Vienna (Austria); Weber, Michael [Department of Radiology, Medical University of Vienna (Austria)

    2010-10-15

    Purpose: To evaluate the prevalence of nephrogenic systemic fibrosis (NSF) in a patient population being at highest risk for developing this disease and to evaluate possible risk factors. Materials and methods: The radiological records of 552 patients with ESRD being on hemodialysis (HD) or peritoneal dialysis (PD) were retrospectively reviewed to identify whether the patients underwent MR-examinations with or without intravenous administration of GBCA. In case of exposure to GBCA, the number of contrast injections, the benchmark and the cumulative doses of GBCA, and possible cofactors regarding pathogenesis of NSF were recorded. Diagnosis of NSF was confirmed either by deep skin biopsy or by review of medical and histopathological records. Data of NSF patients were compared with data of dialysis patients who did not develop NSF after MR-examinations. Results: 146 dialysis patients underwent MRI without i.v.-administration of GBCA. No case of NSF was observed in this patient population. 195/552 patients proved to have a total number of 325 well-documented exposures to GBCA. Seven different types of GBCA were used during these MR-examinations. NSF prevalence rate was 1.6%. One patient died of NSF. Three different types of GBCA were involved in 6 NSF cases. 4/6 proved to be confounded cases. The cumulative dose of GBCA, history of thrombosis, recent surgery, and the combination of HD and PD proved to be significant cofactors for the development of NSF (p < .05). No significant difference regarding residual renal clearance (p = .898) and residual urine volume (p = .083) was found between NSF and non-NSF patients. Conclusion: The prevalence of NSF proved to be much lower in this high risk patient group being exposed to GBCA compared to the literature. NSF was not observed in ESRD patients undergoing MRI without administration of GBCA. Our data support a positive association between cumulative dose of GBCA and development of NSF. No positive association was found

  2. Administrative support of novice science teachers: A multiple case study

    Science.gov (United States)

    Iacuone, Leann

    Novice science teachers leave the confines of colleges and universities to embark on a new adventure in education where they aim to influence young minds, make a difference in the world, and share their love for their content. They have learned their pedagogical skills with the support and assistance of fellow classmates, a supporting professor, and a cooperating teacher. These teachers enter their new place of employment and are met with many unexpected challenges, such as a lack of resources, no one to ask questions of, and a busy staff with already established relationships, causing them to feel an overall lack of support and resulting in many new teachers rethinking their career choice and leaving the field of education within 5 years of entering. This multiple-case study investigated the administrative support 4 novice science teachers received during an academic year and the novice teachers' perceptions of the support they received to answer the following research question: How do novice science teachers who have consistent interactions with administrators develop during their first year? To answer this question, semistructured interviews, reflection journals, observations, resumes, long-range plans, and student discipline referrals were collected. The findings from this study show novice science teachers who had incidents occur in the classroom requiring administrative assistance and guidance felt more confident in enforcing their classroom management policies and procedures as the year progressed to change student behavior. The novice science teachers perceived administrators who provided resources including technology, office supplies, science supplies, and the guidance of a mentor as supportive. Novice science teachers who engaged in dialogue after administrative observations, were provided the opportunity to attend professional development outside the district, and had a mentor who taught the same discipline made more changes to their instructional

  3. The use of cardiac output monitoring to guide the administration of intravenous fluid during hyperthermic intraperitoneal chemotherapy.

    Science.gov (United States)

    Thanigaimani, K; Mohamed, F; Cecil, T; Moran, B J; Bell, J

    2013-12-01

    The optimal strategy for intravenous (IV) fluid management during administration of hyperthermic intraperitoneal chemotherapy (HIPEC) is unclear. In this prospective study we describe the use of a LiDCOrapid™ (LiDCO, Cambridge, UK) cardiac output monitor to guide IV fluid management during cytoreductive surgery (CRS) with HIPEC. The aim of this study was to determine whether cardiac output monitoring will allow close maintenance of physiological parameters during the HIPEC phase. Twenty-five patients who underwent CRS combined with HIPEC were included in the study. Intra-operative IV fluid boluses were titrated using parameters measured by the LiDCOrapid™ monitor. Stroke volume variation was maintained below 10% with fluid boluses and mean arterial pressure was maintained within 20% of the baseline figure with vasopressors. There was no significant change in heart rate and cardiac output. The systemic vascular resistance dropped from an average of 966 dyn.s/cm-5 to 797 dyn s/cm(5) at 60 min during the HIPEC phase (P = 0.62) despite an increase in the dose of phenylepherine. The average total volume of fluid given was 748 ml in the first 30 min and 630 ml in the second 30 min with an average urine output of 307 and 445 ml, respectively. The change in lactate levels was not statistically or clinically significant. LiDCOrapid™ is an effective noninvasive tool for guiding fluid management in this population. It allows the anaesthesiologist to maintain tight control of essential physiological parameters during a phase of the procedure in which there is a risk of renal injury. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

  4. Cationization of immunoglobulin G results in enhanced organ uptake of the protein after intravenous administration in rats and primate

    International Nuclear Information System (INIS)

    Triguero, D.; Buciak, J.L.; Pardridge, W.M.

    1991-01-01

    Cationization of proteins in general enhances the cellular uptake of these macromolecules, and cationized antibodies are known to retain antigen binding properties. Therefore, cationized antibodies may be therapeutic and allow for intracellular immunization. The present studies test the hypothesis that the tissue uptake of cationized immunoglobulin G (IgG) after intravenous administration may be greatly increased relative to the uptake of native proteins. The pharmacokinetics of cationized immunoglobulin G clearance from blood, and the volume of distribution of the cationized or native protein (albumin, IgG) for 10 organs was measured both in anesthetized rats and in an anesthetized adult Macaca irus cynomologous monkey. Initial studies on brain showed that serum factors inhibited uptake of 125I-cationized IgG, but not 3H-cationized IgG. The blood-brain barrier permeability surface area product for 3H-cationized IgG was 0.57 ± 0.04 microliters min-1 g-1. The ratio of the volume of distribution of the 3-H-cationized IgG compared to 3H-labeled native albumin ranged from 0.9 (testis) to 15.7 (spleen) in the rat at 3 hr after injection, and a similarly enhanced organ uptake was observed in the primate. In conclusion, these studies demonstrate that cationization of immunoglobulin greatly increases organ uptake of the plasma protein compared to native immunoglobulins, and suggest that cationization of monoclonal antibodies may represent a potential new strategy for enhancing the intracellular delivery of these proteins

  5. Distribution of Synthetic Cannabinoids JWH-210, RCS-4 and Δ 9-Tetrahydrocannabinol After Intravenous Administration to Pigs.

    Science.gov (United States)

    Schaefer, Nadine; Kettner, Mattias; Laschke, Matthias W; Schlote, Julia; Ewald, Andreas H; Menger, Michael D; Maurer, Hans H; Schmidt, Peter H

    2017-01-01

    Synthetic cannabinoids (SCs) have become an increasing issue in forensic toxicology. Controlled human studies evaluating pharmacokinetic data of SCs are lacking and only few animal studies have been published. Thus, an interpretation of analytical results found in intoxicated or poisoned individuals is difficult. Therefore, the distribution of two selected SCs, namely 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210) and 2-(4-methoxyphenyl)-1-(1- pentyl-indol-3-yl)methanone (RCS-4) as well as Δ9-tetrahydrocannabinol (THC) as reference were examined in pigs. Pigs (n = 6 per drug) received a single intravenous 200 μg/kg BW dose of JWH-210, RCS- 4, or THC. Six hours after administration, the animals were exsanguinated and relevant organs, important body fluids such as bile, and tissues such as muscle and adipose tissue, as well as the bradytrophic specimens dura and vitreous humor were collected. After hydrolysis and solid phase extraction, analysis was performed by LC-MS/MS. To overcome matrix effects of the LC-MS/MS analysis, a standard addition method was applied for quantification. The parent compounds could be detected in every analyzed specimen with the exception of THC that was not present in dura and vitreous humor. Moderate concentrations were present in brain, the site of biological effect. Metabolite concentrations were highest in tissues involved in metabolism and/or elimination Conclusions: Besides kidneys and lungs routinely analyzed in postmortem toxicology, brain, adipose, and muscle tissue could serve as alternative sources, particularly if other specimens are not available. Bile fluid is the most appropriate specimen for SCs and THC metabolites detection. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Distribution of Synthetic Cannabinoids JWH-210, RCS-4 and ∆ 9-Tetrahydrocannabinol After Intravenous Administration to Pigs

    Science.gov (United States)

    Schaefer, Nadine; Kettner, Mattias; Laschke, Matthias W.; Schlote, Julia; Ewald, Andreas H.; Menger, Michael D.; Maurer, Hans H.; Schmidt, Peter H.

    2017-01-01

    Background: Synthetic cannabinoids (SCs) have become an increasing issue in forensic toxicology. Controlled human studies evaluating pharmacokinetic data of SCs are lacking and only few animal studies have been published. Thus, an interpretation of analytical results found in intoxicated or poisoned individuals is difficult. Therefore, the distribution of two selected SCs, namely 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210) and 2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone (RCS-4) as well as ∆9-tetrahydrocannabinol (THC) as reference were examined in pigs. Methods: Pigs (n = 6 per drug) received a single intravenous 200 µg/kg BW dose of JWH-210, RCS-4, or THC. Six hours after administration, the animals were exsanguinated and relevant organs, important body fluids such as bile, and tissues such as muscle and adipose tissue, as well as the bradytrophic specimens dura and vitreous humor were collected. After hydrolysis and solid phase extraction, analysis was performed by LC-MS/MS. To overcome matrix effects of the LC-MS/MS analysis, a standard addition method was applied for quantification. Results: The parent compounds could be detected in every analyzed specimen with the exception of THC that was not present in dura and vitreous humor. Moderate concentrations were present in brain, the site of biological effect. Metabolite concentrations were highest in tissues involved in metabolism and/or elimination. Conclusions: Besides kidneys and lungs routinely analyzed in postmortem toxicology, brain, adipose, and muscle tissue could serve as alternative sources, particularly if other specimens are not available. Bile fluid is the most appropriate specimen for SCs and THC metabolites detection. PMID:27834143

  7. Pharmacokinetics of chloramphenicol following administration of intravenous and subcutaneous chloramphenicol sodium succinate, and subcutaneous chloramphenicol, to koalas (Phascolarctos cinereus).

    Science.gov (United States)

    Black, L A; McLachlan, A J; Griffith, J E; Higgins, D P; Gillett, A; Krockenberger, M B; Govendir, M

    2013-10-01

    Clinically normal koalas (n = 19) received a single dose of intravenous (i.v.) chloramphenicol sodium succinate (SS) (25 mg/kg; n = 6), subcutaneous (s.c.) chloramphenicol SS (60 mg/kg; n = 7) or s.c. chloramphenicol base (60 mg/kg; n = 6). Serial plasma samples were collected over 24-48 h, and chloramphenicol concentrations were determined using a validated high-performance liquid chromatography assay. The median (range) apparent clearance (CL/F) and elimination half-life (t(1/2)) of chloramphenicol after i.v. chloramphenicol SS administration were 0.52 (0.35-0.99) L/h/kg and 1.13 (0.76-1.40) h, respectively. Although the area under the concentration-time curve was comparable for the two s.c. formulations, the absorption rate-limited disposition of chloramphenicol base resulted in a lower median C(max) (2.52; range 0.75-6.80 μg/mL) and longer median tmax (8.00; range 4.00-12.00 h) than chloramphenicol SS (C(max) 20.37, range 13.88-25.15 μg/mL; t(max) 1.25, range 1.00-2.00 h). When these results were compared with susceptibility data for human Chlamydia isolates, the expected efficacy of the current chloramphenicol dosing regimen used in koalas to treat chlamydiosis remains uncertain and at odds with clinical observations. © 2012 John Wiley & Sons Ltd.

  8. A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters.

    Science.gov (United States)

    Loubani, Osama M; Green, Robert S

    2015-06-01

    The aim of this study was to collect and describe all published reports of local tissue injury or extravasation from vasopressor administration via either peripheral intravenous (IV) or central venous catheter. A systematic search of Medline, Embase, and Cochrane databases was performed from inception through January 2014 for reports of adults who received vasopressor intravenously via peripheral IV or central venous catheter for a therapeutic purpose. We included primary studies or case reports of vasopressor administration that resulted in local tissue injury or extravasation of vasopressor solution. Eighty-five articles with 270 patients met all inclusion criteria. A total of 325 separate local tissue injury and extravasation events were identified, with 318 events resulting from peripheral vasopressor administration and 7 events resulting from central administration. There were 204 local tissue injury events from peripheral administration of vasopressors, with an average duration of infusion of 55.9 hours (±68.1), median time of 24 hours, and range of 0.08 to 528 hours. In most of these events (174/204, 85.3%), the infusion site was located distal to the antecubital or popliteal fossae. Published data on tissue injury or extravasation from vasopressor administration via peripheral IVs are derived mainly from case reports. Further study is warranted to clarify the safety of vasopressor administration via peripheral IVs. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Thoracic paravertebral block versus intravenous patient-controlled analgesia for pain treatment in patients with multiple rib fractures.

    Science.gov (United States)

    Yeying, Ge; Liyong, Yuan; Yuebo, Chen; Yu, Zhang; Guangao, Ye; Weihu, Ma; Liujun, Zhao

    2017-12-01

    Objectives To assess the effect of thoracic paravertebral block (PVB) on pain management and preservation of pulmonary function compared with intravenous, patient-controlled analgesia (IVPCA) in patients with multiple rib fractures (MRFs). Methods Ninety patients with unilateral MRFs were included in this prospective study and randomly assigned to the TPVB or IVPCA group. The visual analogue scale (VAS) pain score, blood gas analysis, and bedside spirometry were measured and recorded at different time points after analgesia. Results TPVB and IVPCA provided good pain relief. VAS scores were significantly lower in the TPVB group than in the IVPCA group at rest and during coughing ( P pain relief and preservation of pulmonary function in patients with MRFs.

  10. 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.

  11. Intravenous Contrast Medium Administration for Computed Tomography Scan in Emergency: A Possible Cause of Contrast-Induced Nephropathy

    International Nuclear Information System (INIS)

    Sonhaye, Lantam; Kolou, Bérésa; Tchaou, Mazamaesso; Amadou, Abdoulatif; Assih, Kouméabalo; N'Timon, Bidamin; Adambounou, Kokou; Agoda-Koussema, Lama; Adjenou, Komlavi; N'Dakena, Koffi

    2015-01-01

    The goal of this study was to assess risk for CIN after CT Scan during an emergency and to identify risk factors for the patient. Prospective review of all patients admitted to the emergency room (ER) of the Teaching Hospital of Lomé (Togo) during a 2-year period. CIN was defined as an increase in serum creatinine by 0.5 mg/dL from admission after undergoing CT Scan with intravenous contrast. A total of 620 patients underwent a CT Scan in the emergency room using intravenous contrast and 672 patients took the CT Scan without intravenous contrast. Out of the patients who received intravenous contrast for CT Scan, three percent of them developed CIN during their admission. Moreover, upon discharge no patient had continued renal impairment. No patient required dialysis during their admission. The multivariate analysis of all patients who had serial creatinine levels (including those who did not receive any contrast load) shows no increased risk for acute kidney injury associated intravenous contrast (odds ratio = 0.619, p value = 0.886); only diabetes remains independent risk factor of acute kidney injury (odds ratio = 6.26, p value = 0.031)

  12. The Optimal Route of Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Abciximab During Percutaneous Coronary Intervention; Intravenous Versus Intracoronary

    DEFF Research Database (Denmark)

    Iversen, Allan; Galatius, Søren; Jensen, Jan S

    2008-01-01

    -randomised and retrospective studies or studies with short follow-up. No definite conclusion can be made based on these studies.In this review we present the current knowledge published about the intracoronary administration of Abciximab including the mechanisms behind the potential beneficial effects, and the safety...... and thrombus formation, but other mechanisms, such as suppression of the inflammatory pathways, have also been proposed to contribute to the benefits of Abciximab.The optimal route of administration, i.e. intravenous versus intracoronary, of the first dose has been questioned, but only tested in small, non...

  13. Comparison of intrapulmonary and systemic pharmacokinetics of colistin methanesulfonate (CMS) and colistin after aerosol delivery and intravenous administration of CMS in critically ill patients.

    Science.gov (United States)

    Boisson, Matthieu; Jacobs, Matthieu; Grégoire, Nicolas; Gobin, Patrice; Marchand, Sandrine; Couet, William; Mimoz, Olivier

    2014-12-01

    Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfonate (CMS); however, differences between the intrapulmonary concentrations of the active moiety as a function of the route of administration in critically ill patients have not been precisely documented. In this study, CMS and colistin concentrations were measured on two separate occasions within the plasma and epithelial lining fluid (ELF) of critically ill patients (n = 12) who had received 2 million international units (MIU) of CMS by aerosol delivery and then intravenous administration. The pharmacokinetic analysis was conducted using a population approach and completed by pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulations. The ELF colistin concentrations varied considerably (9.53 to 1,137 mg/liter), but they were much higher than those in plasma (0.15 to 0.73 mg/liter) after aerosol delivery but not after intravenous administration of CMS. Following CMS aerosol delivery, typically, 9% of the CMS dose reached the ELF, and only 1.4% was presystemically converted into colistin. PK-PD analysis concluded that there was much higher antimicrobial efficacy after CMS aerosol delivery than after intravenous administration. These new data seem to support the use of aerosol delivery of CMS for the treatment of pulmonary infections in critical care patients. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  14. New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration.

    Science.gov (United States)

    Berthet, Carole; Castillo, Ximena; Magistretti, Pierre J; Hirt, Lorenz

    2012-01-01

    Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 µl of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 µmol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p mouse brain against ischaemic damage when supplied intracerebroventricularly during reperfusion with behavioural and histological benefits persisting 2 weeks after ischaemia. Importantly, lactate also protects after systemic intravenous administration, a more suitable route of administration in a clinical emergency setting. These findings provide further steps to bring this physiological, commonly available and inexpensive neuroprotectant closer to clinical translation for stroke. Copyright © 2012 S. Karger AG, Basel.

  15. Immunomodulatory effects of intravenous bis-1 f(ab')(2) administration in renal-cell cancer-patients

    NARCIS (Netherlands)

    Janssen, R. A. J.; Kroesen, B. J.; Mesander, G.; Sleijfer, D. T.; The, T. Hauw; Mulder, N. H.; de Leij, L

    We report the immunomodulatory effects of an intravenous treatment with F(ab')(2) fragments of the bispecific monoclonal antibody BIS-1 during subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cell cancer (RCC) patients. BIS-1 is directed against both the CD3 antigen on T cells and the

  16. Rapid alleviation of signs and symptoms of rheumatoid arthritis with intravenous or subcutaneous administration of adalimumab in combination with methotrexate.

    NARCIS (Netherlands)

    Rau, R.; Simianer, S.; Riel, P.L.C.M. van; Putte, L.B.A. van de; Kruger, K.; Schattenkirchner, M.; Allaart, C.F.; Breedveld, F.C.; Kempeni, J.; Beck, K.; Kupper, H.

    2004-01-01

    OBJECTIVE: This randomized, placebo-controlled, double-blind, Phase 1 study assessed the magnitude, onset, and duration of response with intravenous (i.v.) and subcutaneous (s.c.) adalimumab (Humira, Abbott Laboratories) combined with methotrexate (MTX) in patients with active rheumatoid arthritis

  17. Comparison of oral and intravenous routes of administration of dipyridamole for thallium imaging of type I diabetics with end-stage renal disease

    International Nuclear Information System (INIS)

    Boudreau, R.J.; Stony, J.T.; du Cret, R.P.; Kuni, C.C.; Wang, Y.; Wilson, R.F.; Schwartz, J.F.; Castaneda-Zuniga, W.R.

    1989-01-01

    The authors have frequently seen myocardial infarction after renal transplantation in patient with type I diabetes, and treadmill T1-201 testing in these patients have been inadequate. The authors evaluated dipyridamole (DP) as a substitute for treadmill stress. Because intravenous DP was not approved in the United States at the time of the study, the oral formulation wax used for some patients. The authors have prospectively evaluated 80 uremic diabetics (40 received oral T1-201; 40 received intravenous T1-201). Angiogram and scan observers were blinded. There was not difference in the accuracy of the two routes of administration. Pooling the data gave a sensitivity of 86% and a specificity of 79%. However, their disease prevalence was high (52%), which precluded the use of any screening test. The authors now have recommended angiography for these patients

  18. 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.)

  19. Intravenous Administration Is an Effective and Safe Route for Cancer Gene Therapy Using the Bifidobacterium-Mediated Recombinant HSV-1 Thymidine Kinase and Ganciclovir

    Directory of Open Access Journals (Sweden)

    Huicong Zhou

    2016-06-01

    Full Text Available The herpes simplex virus thymidine kinase/ganciclovir (HSV TK/GCV system is one of the best studied cancer suicide gene therapy systems. Our previous study showed that caspase 3 expression was upregulated and bladder tumor growth was significantly reduced in rats treated with a combination of Bifidobacterium (BF and HSV TK/GCV (BF-rTK/GCV. However, it was raised whether the BF-mediated recombinant thymidine kinase combined with ganciclovir (BF-rTK/GCV was safe to administer via venous for cancer gene therapy. To answer this question, the antitumor effects of BF-rTK/GCV were mainly evaluated in a xenograft nude mouse model bearing MKN-45 gastric tumor cells. The immune response, including analysis of cytokine profiles, was analyzed to evaluate the safety of intramuscular and intravenous injection of BF-rTK in BALB/c mice. The results suggested that gastric tumor growth was significantly inhibited in vivo by BF-rTK/GCV. However, the BF-rTK/GCV had no effect on mouse body weight, indicating that the treatment was safe for the host. The results of cytokine profile analysis indicated that intravenous injection of a low dose of BF-rTK resulted in a weaker cytokine response than that obtained with intramuscular injection. Furthermore, immunohistochemical analysis showed that intravenous administration did not affect the expression of immune-associated TLR2 and TLR4. Finally, the BF-rTK/GCV inhibited vascular endothelial growth factor (VEGF expression in mouse model, which is helpful for inhibiting of tumor angiogenesis. That meant intravenous administration of BF-rTK/GCV was an effective and safe way for cancer gene therapy.

  20. A Comparative In Vivo Scrutiny of Biosynthesized Copper and Zinc Oxide Nanoparticles by Intraperitoneal and Intravenous Administration Routes in Rats.

    Science.gov (United States)

    C, Ashajyothi; K Handral, Harish; Kelmani R, Chandrakanth

    2018-04-03

    During the present time, anti-microbial features of copper (Cu) and zinc oxide (ZnO) nanoparticles (NPs) are extensively used to combat the growth of pathogenic microbes. CuNPs and ZnONPs are recurrently used in cosmetics, medicine and food additives, and their potential for toxic impacts on human and ecosystem is of high concern. In this study, the fate and toxicity of 16- to 96-nm-ranged biosynthesized copper (Bio-CuNPs) and zinc oxide (Bio-ZnONPs) was assessed in male Wistar rats. In vivo exposures of the two nanoparticles are achieved through two different administration routes namely, intraperitoneal (i/p) and intravenous (i/v) injections. The three different concentrations, no observable adverse effect concentration (NOAEC), inhibitory concentration (IC 50 ) and total lethal concentration (TLC), were appraised at the dose range of 6.1 to 19.82 μg/kg and 11.14 to 30.3 μg/kg for Bio-CuNPs and Bio-ZnONPs respectively, for both i/p and i/v routes on 14th and 28th day of observation. These dose ranges are considered based on the previous study of antibacterial dose on multidrug-resistant pathogenic bacteria. In this study, we investigated the toxic effect of Bio-CuNPs and Bio-ZnONPs on animal behaviour, animal mass, haematologic indices, organ indices and histopathology of liver, spleen, kidney and brain organs. We found that i/v and i/p administration of Bio-ZnONPs in three different doses did not cause mortality and body weight was slightly reduced up to second week of administration compared with the vehicle control group. At the dose ranges of 11-16 μg/kg (i/v) and 24-30 μg/kg (i/p), no significant changes were observed in the serum creatinine level as well as serum ALT, serum AST level and ALP level which were 40.7 mg/dl, 37.9 IU/L and 82.4 IU/L normal as compared to vehicle control on 14th and 28th day of observation. These findings are confirmed in liver, kidney and spleen indices and histopathology studies. Furthermore, liver and kidney injury

  1. Qualitative and quantitative volumetric evaluation of the efficacy of intravenous immunoglobulin in multiple sclerosis: preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Teksam, M. [Department of Radiology, Gazi University Medical School, Ankara (Turkey); Department of Radiology, Medical School, University of Minnesota, MN(United States); Tali, T.; Isik, S. [Department of Radiology, Gazi University Medical School, Ankara (Turkey); Kocer, B. [Department of Neurology, Gazi University Medical School, Ankara (Turkey)

    2000-12-01

    We conducted a double-blind, placebo-controlled study in 13 patients (aged 22 to 54 years) with relapsing-remitting multiple sclerosis (MS). They were randomly assigned to receive a loading dose of immunoglobulin IgG, 0.4 g/kg body weight/day for 5 consecutive days, followed by single booster doses of 0.4 g/kg/day, or placebo, once a month for 9 months. MRI was obtained before and during the 3rd and 6th months of treatment; examinations in the 9th and 12th months were planned. Qualitative and quantitative blinded assessments were performed. There were seven patients who received active treatment and six who received placebo. Statistical analysis was performed by the Wilcoxon test. A decrease in the size and number of lesions was observed on MRI in five patients (71 %) in the treatment group, and in two (33 %) of the placebo group at 3-month follow-up. At 6 months follow-up MRI, a decrease in the amount of lesions was observed in all patients treated with IV IgG, and in two (33 %) of the placebo group; four patients (66 %) receiving placebo showed an increase. Quantitative analysis showed a statistically significant decrease in the volume of lesions in treatment group at both 3 and 6 month follow-up. There was no statistically significant change in the placebo group. (orig.)

  2. Qualitative and quantitative volumetric evaluation of the efficacy of intravenous immunoglobulin in multiple sclerosis: preliminary report

    International Nuclear Information System (INIS)

    Teksam, M.; Tali, T.; Isik, S.; Kocer, B.

    2000-01-01

    We conducted a double-blind, placebo-controlled study in 13 patients (aged 22 to 54 years) with relapsing-remitting multiple sclerosis (MS). They were randomly assigned to receive a loading dose of immunoglobulin IgG, 0.4 g/kg body weight/day for 5 consecutive days, followed by single booster doses of 0.4 g/kg/day, or placebo, once a month for 9 months. MRI was obtained before and during the 3rd and 6th months of treatment; examinations in the 9th and 12th months were planned. Qualitative and quantitative blinded assessments were performed. There were seven patients who received active treatment and six who received placebo. Statistical analysis was performed by the Wilcoxon test. A decrease in the size and number of lesions was observed on MRI in five patients (71 %) in the treatment group, and in two (33 %) of the placebo group at 3-month follow-up. At 6 months follow-up MRI, a decrease in the amount of lesions was observed in all patients treated with IV IgG, and in two (33 %) of the placebo group; four patients (66 %) receiving placebo showed an increase. Quantitative analysis showed a statistically significant decrease in the volume of lesions in treatment group at both 3 and 6 month follow-up. There was no statistically significant change in the placebo group. (orig.)

  3. Comparative kinetics of serum and vitreous humor digoxin concentrations in a guinea pig model. Part I: Intravenous administration of digoxin

    Energy Technology Data Exchange (ETDEWEB)

    Donnelly, B.; Balkon, J.; Bidanset, J.H.; Belmonte, A.; Barletta, M.; Manning, T. (Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John' s University, Jamaica, NY (USA))

    1991-03-01

    The pharmacokinetics of a single intravenous dose of digoxin in the guinea pig was investigated with emphasis on the penetration of digoxin into the vitreous humor. A controlled study was undertaken and data was collected which indicated that digoxin follows an open, two-compartment pharmacokinetic model with a terminal half-life of 318 minutes. The data indicated that the ratio of vitreous concentrations to serum concentrations were determined to be equal following an initial tissue distribution phase.

  4. Comparison of different administration of ketamine and intravenous tramadol hydrochloride for postoperative pain relief and sedation after pediatric tonsillectomy.

    Science.gov (United States)

    Yenigun, Alper; Et, Tayfun; Aytac, Sirin; Olcay, Betul

    2015-01-01

    Tonsillectomy is the oldest and most frequently performed surgical procedure practiced by ear, nose, and throat physicians. In this study, our aim was to compare the analgesic effects of peritonsillar, rectal, as well as intravenous infiltration of ketamine and intravenous tramadol hydrochloride infiltration for postoperative pain relief and sedation after tonsillectomy in children. This randomized controlled study evaluated the effects of peritonsillar, intravenous, and rectal infiltration of ketamine in children undergoing adenotonsillectomy. One hundred twenty children who were categorized under American Society of Anesthesiologists classes I to II were randomized to 4 groups of 30 members each. Group 1 received intravenous (IV) ketamine (0.5 mg/kg), group 2 received rectal ketamine (0.5 mg/kg), group 3 received local peritonsillar ketamine (2 mg/kg), and the control group received IV tramadol hydrochloride infiltration (2 mg/kg). Children's Hospital of Eastern Ontario Pain Scale scores and Wilson sedation scale were recorded at minutes 1, 15, 30, 60 as well as hours 2, 12, and 24 postoperatively. The patients were interviewed on the day after the surgery to assess the postoperative pain and sedation. All the routes of infiltration of ketamine were as effective as those of tramadol hydrochloride (P > 0.05). A statistically significant difference was observed between IV infiltrations and all groups during the assessments at hours 6 and 24. The analgesic efficacy of IV ketamine was found especially higher at hours 6 and 24 (P(6) = 0.045, P(24) = 0.011). Perioperative, low-dose IV, rectal, or peritonsillar ketamine infiltration provides efficient pain relief without any adverse effects in children who would undergo adenotonsillectomy.

  5. Comparative kinetics of serum and vitreous humor digoxin concentrations in a guinea pig model. Part I: Intravenous administration of digoxin

    International Nuclear Information System (INIS)

    Donnelly, B.; Balkon, J.; Bidanset, J.H.; Belmonte, A.; Barletta, M.; Manning, T.

    1991-01-01

    The pharmacokinetics of a single intravenous dose of digoxin in the guinea pig was investigated with emphasis on the penetration of digoxin into the vitreous humor. A controlled study was undertaken and data was collected which indicated that digoxin follows an open, two-compartment pharmacokinetic model with a terminal half-life of 318 minutes. The data indicated that the ratio of vitreous concentrations to serum concentrations were determined to be equal following an initial tissue distribution phase

  6. Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy

    Directory of Open Access Journals (Sweden)

    Lee Young-Ho

    2012-03-01

    Full Text Available Abstract Backgrounds We conducted a pilot study of the infusion of intravenous autologous cord blood (CB in children with cerebral palsy (CP to assess the safety and feasibility of the procedure as well as its potential efficacy in countering neurological impairment. Methods Patients diagnosed with CP were enrolled in this study if their parents had elected to bank their CB at birth. Cryopreserved CB units were thawed and infused intravenously over 10~20 minutes. We assessed potential efficacy over 6 months by brain magnetic resonance imaging (MRI-diffusion tensor imaging (DTI, brain perfusion single-photon emission computed tomography (SPECT, and various evaluation tools for motor and cognitive functions. Results Twenty patients received autologous CB infusion and were evaluated. The types of CP were as follows: 11 quadriplegics, 6 hemiplegics, and 3 diplegics. Infusion was generally well-tolerated, although 5 patients experienced temporary nausea, hemoglobinuria, or urticaria during intravenous infusion. Diverse neurological domains improved in 5 patients (25% as assessed with developmental evaluation tools as well as by fractional anisotropy values in brain MRI-DTI. The neurologic improvement occurred significantly in patients with diplegia or hemiplegia rather than quadriplegia. Conclusions Autologous CB infusion is safe and feasible, and has yielded potential benefits in children with CP.

  7. Is pre-emptive administration of ketamine a significant adjunction to intravenous morphine analgesia for controlling postoperative pain? A randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Fiorelli, Alfonso; Mazzella, Antonio; Passavanti, Beatrice; Sansone, Pasquale; Chiodini, Paolo; Iannotti, Mario; Aurilio, Caterina; Santini, Mario; Pace, Maria Caterina

    2015-09-01

    To evaluate if the pre-emptive administration of ketamine would potentiate the effect of intravenous morphine analgesia in the management of post-thoracotomy pain. This was a unicentre, double-blind, placebo-controlled, parallel-group, prospective study. Patients were randomly assigned to receive 1 mg/kg ketamine (ketamine group) or an equivalent dose of normal saline (placebo group) before thoracotomy in 1:1 ratio. All patients received postoperatively intravenous morphine administration as additional analgesic regimen. Primary end-point was the pain relief measured with Visual Analogue Scale at rest. The secondary end-points were the reduction of inflammatory response expressed by plasma C-reactive protein levels, the morphine consumption and the rate of side effects. The measurements were carried out 6, 12, 24, 36 and 48 hours postoperatively. A total of 75 patients were randomized of whom 38 were allocated to ketamine group and 37 to placebo group. Baseline characteristics were comparable. Ketamine compared with placebo group showed a significant reduction of pain scores (P = 0.01), C-reactive protein (P morphine consumption (P psychological side effects related to the use of ketamine were registered. The administration of ketamine before surgery may be an effective adjunct to intravenous morphine analgesia in acute post-thoracotomy pain management. In ketamine group, satisfaction of pain relief was significantly higher with a significant reduction of inflammatory response and morphine consumption compared with placebo group. Our results, if confirmed by larger studies, may be of clinical relevance in situations where epidural analgesia or other analgesic procedures different from systemic opioid analgesia are unavailable or contraindicated. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  8. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells has a neutral effect on obesity-induced diabetic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Sebastián D Calligaris

    2013-01-01

    Full Text Available Obesity is a major global health issue. Obese patients develop metabolic syndrome, which is a cluster of clinical features characterized by insulin resistance and dyslipidemia. Its cardiac manifestation, diabetic cardiomyopathy, leads to heart failure. Bone marrow-derived multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSC are envisioned as a therapeutic tool not only for cardiovascular diseases but also for other degenerative conditions. Our aim was to evaluate whether the intravenous administration of MSC modifies cardiac dysfunction in obese mice. To this end, C57BL/6 mice were fed a regular (normal or high-fat diet (obese. Obese animals received the vehicle (obese, a single dose (obese + 1x MSC or three doses (obese + 3x MSC of 0.5x10(6 syngeneic MSC. Two to three months following MSC administration, cardiac function was assessed by cardiac catheterization, at basal condition and after a pharmacological stress. Compared to normal mice, obese mice presented hyperglycemia, hyperinsulinemia, hypercholesterolemia and cardiac dysfunction after stress condition. Exogenous MSC neither improved nor impaired this cardiac dysfunction. Thus, intravenous administration of MSC has neutral effect on obesity-induced diabetic cardiomyopathy

  9. Comparison between the in vivo rate of metabolism of prostaglandin I2 and its blood-pressure-lowering response after intravenous administration in the rat.

    Science.gov (United States)

    Pace-Asciak, C R; Rosenthal, A; Domazet, Z

    1979-07-27

    Intravenous bolus injection of prostaglandin I2 in the Inactin-anaesthetised rat produces a slow dose-dependant vasodepression which reaches maximum approximately 15 s. after injection. Administration of 9 beta-[3H1]-prostaglandin I2 by the same route followed by serial arterial sampling and TLC analysis revealed a slow conversion into one less polar metabolite starting after 20 s and reaching 40% by two minutes in the circulation. These experiments indicate that prostaglandin I2 survives pulmonary transit for a sufficiently long time to elicit a biological action. Thus its continuous systemic vascular synthesis could play an important role in the control of hypertension.

  10. 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

  11. Comparison of the Intraperitoneal, Retroorbital and per Oral Routes for F 18 FDG Administration as Effective Alternatives to Intravenous Administration in Mouse Tumor Models Using Small Animal PET/CT Studies

    International Nuclear Information System (INIS)

    Kim, Chulhan; Kim, In Hye; Kim, Seo il; Kim, Young Sang; Kang, Se Hun; Moon, Seung Hwan; Kim, Tae Sung; Kim, Seok ki

    2011-01-01

    We compared alternative routes for 18F fluorodeoxyglucose (FDG) administration, such as the retroorbital (RO), intraperitoneal (IP) and per oral (PO) routes, with the intravenous (IV) route in normal tissues and tumors of mice. CRL 1642 (ATCC, Lewis lung carcinoma) cells were inoculated in female BALB/c nu/nu mice 6 to 10 weeks old. When the tumor grew to about 9mm in diameter, positron emission tomography (PET) scans were performed after FDG administration via the RO, IP, PO or IV route. Additional serial PET scans were performed using the RO, IV or IP route alternatively from 5 to 29 days after the tumor cell injection. There was no significant difference in the FDG uptake in normal tissues at 60 min after FDG administration via RO, IP and IV routes. PO administration, however, showed delayed distribution and unwanted high gastrointestinal uptake. Tumoral uptake of FDG showed a similar temporal pattern and increased until 60 min after FDG administration in the RO, IP and IV injection groups. In the PO administration group, tumoral uptake was delayed and reduced. There was no statistical difference among the RO, IP and IV administration groups for additional serial PET scans. RO administration is an effective alternative route to IV administration for mouse FDG PET scans using normal mice and tumor models. In addition, IP administration can be a practical alternative in the late phase, although the initial uptake is lower than those in the IV and RO groups.

  12. Effect of intravenous administration of dextrose or lactated Ringer's solution on seizure development in dogs after cervical myelography with metrizamide

    International Nuclear Information System (INIS)

    Gray, P.R.; Lowrie, C.T.; Wetmore, L.A.

    1987-01-01

    The effect of fluid (5% dextrose in water or lactated Ringer's solution) administered intravenously on the development of seizures after cervical myelography with metrizamide was studied in 10 dogs. In a crossover experimental design, 8 dogs were used twice. Urine output was measured during the second part of the study to determine whether diuresis was a factor affecting seizure development. Dogs given 5% dextrose in water had significantly (P less than 0.05) fewer seizures than did dogs given lactated Ringer's solution. This was attributed to an increase in CSF glucose concentration and was not associated with diuresis

  13. 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.

  14. 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.

  15. Evaluating the Frequency of Errors in Preparation and Administration of Intravenous Medications in the Intensive Care Unit of Shahid-Sadoughi Hospital in Yazd

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    SeyedMojtaba Sohrevardi

    2015-10-01

    Full Text Available Background: In most Iranian hospitals, the nurses in the wards prepare intravenous (IV drugs and unfortunately pharmacists are not involved in this process. The severity of the patients in Intensive Care Unit (ICU heightens the risk of errors. More over the frequency of using IV drugs in this unit is high, so we decided to determine the frequency and types of errors, which occur in the preparation and administration of commonly, used IV medications in an ICU.Method: A prospective cross sectional study was performed from November 2013 to August 2014, in the intensive care unit in Shahid-Sadoughi hospital in Yazd. Medication errors occurred in the process of preparation and administration of IV drugs, were recorded by a pharmacy student and were evaluated by direct observation, according to the method established by Barker and McConnell.Results: A total number of 843 intravenous doses were evaluated. The most common type of error (34.26% was the injection of IV doses faster than the recommended rate followed by preparation (15.69%, administration (9.23% and compatibility with doctor’s order (6.24%. Amikacin was the most common drug involved in errors (41.67%. Most of errors were occurred at afternoon (8 p.m, 28.36%.Conclusion: According to our study the rate of errors in preparation and administration of IV drugs was high in this ICU. Employing more nurses, using developed medical instruments and clinical pharmacists can help to decrease these errors and improve the quality of patient care.

  16. Evaluation of clinical and paraclinical effects of intraosseous vs intravenous administration of propofol on general anesthesia in rabbits.

    Science.gov (United States)

    Mazaheri-Khameneh, Ramin; Sarrafzadeh-Rezaei, Farshid; Asri-Rezaei, Siamak; Dalir-Naghadeh, Bahram

    2012-01-01

    This prospective study aimed to compare the intraosseous (IO) and intravenous (IV) effects of propofol on selected blood parameters and physiological variables during general anesthesia in rabbits. Thirty New Zealand White rabbits were studied. Six rabbits received IV propofol (group 1) and another 6 rabbits, were injected propofol intraosseously (Group 2) for 30 minutes (experimental groups). Rabbits of the third and fourth groups received IV and IO normal saline at the same volume given to the experimental groups, respectively. In the fifth group IO cannulation was performed but neither propofol nor normal saline were administered. Blood profiles were assayed before induction and after recovery of anesthesia. Heart and respiratory rates, rectal temperature, saturation of peripheral oxygen and mean arterial blood pressure were recorded. Heart rate increased significantly 1 to 5 minutes after induction of anesthesia in experimental groups (P anesthesia in rabbits with limited vascular access.

  17. Effects of intravenous bumetanide administration on renal haemodynamics and proximal and distal tubular sodium reabsorption in conscious rats

    Energy Technology Data Exchange (ETDEWEB)

    Shalmi, M.; Petersen, J.S.; Christensen, S. (Department of pharmacology, University of Copenhagen (Denmark))

    1989-01-01

    The renal effects of 0.02-62.5 mg/kg bumetanide given as intravenous bolus injections were studied in water diuretic conscious rats. Clearances of {sup 14}C-tetraethylammonium, {sup 3}H-inulin and lithium were used as markers for renal plasma flow (RPF), glomerular filtion rate (GFR) and proximal tubular output, respectively. Bumetanide caused biphasic, transient and dose-independent changes in the renal haemodynamics without significant alterations of the filtration fraction. At dose-levels above 0.02 mg/kg bumetanide increased urine flow, absolute and fractional Na excretion as well as the indices for fractional output of Na from the proximal tubules (C{sub Li}/C{sub I}n) and the distal nephron segments (C{sub Na}/C{sub Li}). The changes in C{sub Li}/C{sub In} became maximal at doses above 0.5 mg/kg, whereas C{sub Na}/C{sub Li} was increased with the dose up to 12.5 mg/kg. Paradoxically, doses above 12.5 mg/kg were less natriuretic due to a decrease of C{sub Na}/C{sub Li}. It is concluded that in rats bumetanide is an effective although short-acting diuretic when administered intravenously. When comparing peak responses bumetanide is equipotent to furosemide but has a lower maximal efficacy. Judged from the changes in fractional lithium excretion, the natriuretic effect of bumetanide is effected by inhibition of Na reabsorption in the proximal tubule in addition to the well-known effect on the distal nephron segment. (author).

  18. Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS.

    Science.gov (United States)

    Li, Shuping; Teng, Liang; Liu, Wei; Cheng, Xuemei; Jiang, Bo; Wang, Zhengtao; Wang, Chang-Hong

    2016-09-01

    Context The β-carboline alkaloid harmane is widely distributed in common foods, beverages and hallucinogenic plants. Harmane exerts potential in therapies for Alzheimer's and depression diseases. However, little information on its dynamic metabolic profiles and pharmacokinetics in vivo is currently available. Objective This study investigates the dynamic metabolic profiles and pharmacokinetic properties of harmane and its metabolites in rats in vivo. Materials and methods A highly selective, sensitive and rapid ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and well-validated for simultaneous quantitative determination of harmane and its uncertain endogenous metabolite harmine, as well as for semiquantitative determination of 10 harmane metabolites in rats after intravenous injection and oral administration of harmane at 1.0 and 30.0 mg/kg, respectively. Results The calibration curves of harmane and harmine showed excellent linearity within the concentration range of 1-2000 ng/mL with acceptable accuracy, precision, selectivity, recovery, matrix effect and stability. Ten metabolites, including harmane but not harmine, were detected and identified after intravenous and oral administration of harmane. The absolute bioavailability of harmane following an oral dose was 19.41 ± 3.97%. According to the AUC0-t values of all the metabolites, the metabolic levels of phase II metabolites were higher than those of phase I metabolites, and the sulphation pathways were the dominant metabolic routes for harmane in both routes of administration. Discussion and conclusion The pharmacokinetic properties of harmane and its 10 metabolites in rats were determined. Sulphate conjugation was the predominant metabolic process of harmane in rats.

  19. Associations Between Hydration Status, Intravenous Fluid Administration, and Outcomes of Patients Infected With Shiga Toxin-Producing Escherichia coli: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Grisaru, Silviu; Xie, Jianling; Samuel, Susan; Hartling, Lisa; Tarr, Phillip I; Schnadower, David; Freedman, Stephen B

    2017-01-01

    The associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin-producing Escherichia coli (STEC) remain unclear. To determine the relationship between hydration status, the development and severity of hemolytic uremic syndrome (HUS), and adverse outcomes in STEC-infected individuals. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials via the OvidSP platform, PubMed via the National Library of Medicine, CINAHL Plus with full text, Scopus, Web of Science, ClinicalTrials.gov, reference lists, and gray literature were systematically searched. Two reviewers independently identified studies that included patients with hydration status documentation, proven or presumed STEC infection, and some form of HUS that developed. No language restrictions were applied. Two reviewers independently extracted individual study data, including study characteristics, population, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale; strength of evidence was adjudicated using the Grading of Recommendations Assessment, Development, and Evaluation method. Meta-analyses were conducted using random-effects models. Development of HUS, complications (ie, oligoanuric renal failure, involvement of the central nervous system, or death), and interventions (ie, renal replacement therapy). Eight studies comprising 1511 patients (all children) met eligibility criteria. Unpublished data were provided by the authors of 7 published reports. The median risk-of-bias score was 7.5 (range, 6-9). No studies evaluated the effect of hydration during STEC infections on the risk for HUS. A hematocrit value greater than 23% as a measure of hydration status at presentation with HUS was associated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95% CI, 1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95% CI, 1.50-17.57]; I2 = 55%). Compared with

  20. Relapse of Neuromyelitis Optica Spectrum Disorder Associated with Intravenous Lidocaine

    Directory of Open Access Journals (Sweden)

    Akiyuki Uzawa

    2011-01-01

    Full Text Available Lidocaine unmasks silent symptoms and eases neuropathic pain in multiple sclerosis patients; however, the effects of lidocaine in neuromyelitis optica have never been reported. We describe the case of a 59-year-old Japanese woman with neuromyelitis optica spectrum disorder who developed optic neuritis 1 day after intravenous lidocaine injection for treating allodynia. Her symptom seemed to result from a relapse of neuromyelitis optica induced by lidocaine administration, and not because of the transient effects of intravenous lidocaine administration. The possibility that lidocaine administration results in relapse of neuromyelitis optica due to its immunomodulating effects cannot be ruled out.

  1. Effect of intravenous sodium salicylate administration prior to castration on plasma cortisol and electroencephalography parameters in calves.

    Science.gov (United States)

    Bergamasco, L; Coetzee, J F; Gehring, R; Murray, L; Song, T; Mosher, R A

    2011-12-01

    Nociception is an unavoidable consequence of many routine management procedures such as castration in cattle. This study investigated electroencephalography (EEG) parameters and cortisol levels in calves receiving intravenous sodium salicylate in response to a castration model. Twelve Holstein calves were randomly assigned to the following groups: (i) castrated, untreated controls, (ii) 50 mg/kg sodium salicylate IV precastration, were blood sampled at 0, 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 240, 360, and 480 min postcastration. The EEG recording included baseline, castration, immediate recovery (0-5 min after castration), middle recovery (5-10 min after castration), and late recovery (10-20 min after castration). Samples were analyzed by competitive chemiluminescent immunoassay and fluorescence polarization immunoassay for cortisol and salicylate, respectively. EEG visual inspection and spectral analysis were performed. Statistical analyses included anova repeated measures and correlations between response variable. No treatment effect was noted between the two groups for cortisol and EEG measurements, namely an attenuation of acute cortisol response and EEG desynchronization in sodium salicylate group. Time effects were noted for EEG measurements, cortisol and salicylates levels. Significant correlations between cortisol and EEG parameters were noted. These findings have implications for designing effective analgesic regimens, and they suggest that EEG can be useful to monitor pain attributable to castration. © 2011 Blackwell Publishing Ltd.

  2. Plasma pharmacokinetics, tissue distribution and excretion of MnDPDP in the rat and dog after intravenous administration

    International Nuclear Information System (INIS)

    Hustvedt, S.O.

    1997-01-01

    Purpose: To investigate distribution and excretion of mangafodipir (MnDPDP, Teslascan) in the rat and dog. Material and Methods: Formulations of either 14 C-MnDPDP or 54 MnDPDP were injected intravenously at near clinical doses in rats and dogs. Results: The manganese (Mn) moeity is rapidly removed from plasma with an elimination half-life of less than 25 min in both species, reflecting a rapid distribution to the tissues and an early excretion. The plasma clearance of the DPDP moeity is slower than that of Mn and it appears to distribute into the extracellular fluid. Mn is distributed largely to the liver, pancreas and kidneys, and in pregnant rats, also to foetal liver and bones. No transplacental passage of DPDP could be detected. The metal is mainly excreted by the faecal route, with a small fraction eliminated early in the urine. DPDP is rapidly and essentially completely excreted in the urine, consistent with the glomerular filtration rate. (orig./AJ)

  3. Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

    Science.gov (United States)

    Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jiménez-Escrig, Adriano; Richart López, Luis Alberto; Bazán, Eulalia

    2012-01-01

    Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

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

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    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

  5. 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

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    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.

  6. 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

  7. 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.

  8. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings.

    Science.gov (United States)

    Li, Jie; Li, Xin; Ren, Yu-Shan; Lv, Yuan-Yuan; Zhang, Jun-Sheng; Xu, Xiao-Li; Wang, Xian-Zhen; Yao, Jing-Chun; Zhang, Gui-Min; Liu, Zhong

    2017-01-01

    Although arctigenin ( AG ) has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro . In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK) profiles of AG with different drug-delivery manners, including intravenous (i.v), hypodermic injection (i.h), and sublingual (s.l) administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate 100%), and a strong elimination ability ( t 1/2 beagle dog (25.9 ± 3.24%) > rat (15.7 ± 9%) > monkey (3.69 ± 0.12%). This systematic investigation of pharmacokinetic profiles of arctigenin (AG) in vivo and in vitro is worthy of further exploration.

  9. Considerations on prevention of phlebitis and venous pain from intravenous prostaglandin E(1) administration by adjusting solution pH: in vitro manipulations affecting pH.

    Science.gov (United States)

    Kohno, Emiko; Nishikata, Mayumi; Okamura, Noboru; Matsuyama, Kenji

    2008-01-01

    Prostaglandin E(1) (PGE(1); Alprostadil Alfadex) is a potent vasodilator and inhibitor of platelet aggregation used to treat patients with peripheral vascular disease. The main adverse effects of intravenous PGE(1) administration, phlebitis and venous pain, arise from the unphysiologically low pH of infusion solutions. When PGE(1) infusion solutions with a pH value greater then 6 are used, phlebitis and venous pain are considered to be avoidable. Beginning with a PGE(1) infusion solution with pH greater than 6, we add the amount of 7% sodium bicarbonate needed to bring the solution to pH 7.4 if phlebitis or venous pain develops. In the present study we established a convenient nomogram showing the relationship between the titratable acidity of various infusion solutions and the volume of 7% sodium bicarbonate required to attain pH 7.4 for preventing the phlebitis and venous pain associated with PGE(1) infusion.

  10. Cerebral Microbleeds are an Independent Predictor of Hemorrhagic Transformation Following Intravenous Alteplase Administration in Acute Ischemic Stroke.

    Science.gov (United States)

    Nagaraja, Nandakumar; Tasneem, Nudrat; Shaban, Amir; Dandapat, Sudeepta; Ahmed, Uzair; Policeni, Bruno; Olalde, Heena; Shim, Hyungsub; Samaniego, Edgar A; Pieper, Connie; Ortega-Gutierrez, Santiago; Leira, Enrique C; Adams, Harold P

    2018-05-01

    Intravenous alteplase (rt-PA) increases the risk of hemorrhagic transformation of acute ischemic stroke. The objective of our study was to evaluate clinical, laboratory, and imaging predictors on forecasting the risk of hemorrhagic transformation following treatment with rt-PA. We also evaluated the factors associated with cerebral microbleeds that increase the risk of hemorrhagic transformation. Consecutive patients with acute ischemic stroke admitted between January 1, 2009 and December 31, 2013 were included in the study if they received IV rt-PA, had magnetic resonance imaging (MRI) of the brain on admission, and computed tomography or MRI of the brain at 24 (18-36) hours later to evaluate for the presence of hemorrhagic transformation. The clinical data, lipid levels, platelet count, MRI, and computed tomography images were retrospectively reviewed. The study included 366 patients, with mean age 67 ± 15 years; 46% were women and 88% were white. The median National Institutes of Health Stroke Scale (NIHSS) score was 6 (interquartile range 3-15). Hemorrhagic transformation was observed in 87 (23.8%) patients and cerebral microbleeds were noted in 95 (25.9%). Patients with hemorrhagic transformation tended to be older, nonwhite, have atrial fibrillation, higher baseline NIHSS score, lower cholesterol and triglyceride levels, and cerebral microbleeds and nonlacunar infarcts. Patients with cerebral microbleeds were more likely to be older, have hypertension, hyperlipidemia, previous history of stroke, and prior use of antithrombotics. On multivariate analysis race, NIHSS score, nonlacunar infarct, and presence of cerebral microbleeds were independently associated with hemorrhagic transformation following treatment with rt-PA. Presence of cerebral microbleeds is an independent predictor of hemorrhagic transformation of acute ischemic stroke following treatment with rt-PA. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights

  11. Impact of Solutol HS 15 on the pharmacokinetic behaviour of colchicine upon intravenous administration to male Wistar rats.

    Science.gov (United States)

    Bittner, Beate; González, Roberto Carlos Bravo; Walter, Isabelle; Kapps, Martin; Huwyler, Jörg

    2003-05-01

    In the current investigation, the alkaloid colchicine was administered intravenously to male Wistar rats both as a solution in isotonic sodium chloride (NaCl 0.9%, control group) and in NaCl 0.9%:Solutol HS 15 (95:5) at 1.5 mg/kg. At predetermined time points, plasma and urine were collected from the animals and analysed for colchicine and its demethylated metabolites by LC/MS-MS. In the presence of Solutol HS 15, colchicine clearance (CI) was significantly decreased and its maximum plasma concentration (c(max)) was significantly increased as compared to the control group (CI: 15.6+/-7.0 ml/min/kg vs 34.3+/-2.3 ml/min/kg; c(max) 3055.1+/-587.4 h vs 1260.1+/-223.7 h; pSolutol HS 15 treated group (41.50+/-3.23 vs 1.17+/-0.41% of total dose; pSolutol HS 15 compared with surfactant-free incubations (overall means: 72.25+/-0.50% for FF, 0.80+/-0.02 for lambda, 0.46+/-0.04 for K(e)). In vitro, in rat hepatocytes, the clearance of colchicine was significantly reduced at 0.003% Solutol HS 15 present in the incubation medium (0.86+/-0.15 microl/min/10(-6) cells vs 1.46+/-0.06 microl/min/10(-6) cells). As colchicine exhibits a comparatively high aqueous solubility, an impact of Solutol HS 15 on the solubility of the alkaloid is very unlikely to be a reason for the observed effect. Therefore, our results indicate that the most likely reasons for the changed pharmacokinetic behaviour of colchicine in the presence of Solutol HS 15 are alterations of metabolism and/or transport as well as distribution and elimination processes. Copyright 2003 John Wiley & Sons, Ltd.

  12. Evaluation of clinical and paraclinical effects of intraosseous vs intravenous administration of propofol on general anesthesia in rabbits

    Directory of Open Access Journals (Sweden)

    Ramin Mazaheri-Khameneh

    2012-06-01

    Full Text Available This prospective study aimed to compare the intraosseous (IO and intravenous (IV effects of propofol on selected blood parameters and physiological variables during general anesthesia in rabbits. Thirty New Zealand White rabbits were studied. Six rabbits received IV propofol (group 1 and another 6 rabbits, were injected propofol intraosseously (Group 2 for 30 minutes (experimental groups. Rabbits of the third and fourth groups received IV and IO normal saline at the same volume given to the experimental groups, respectively. In the fifth group IO cannulation was performed but neither propofol nor normal saline were administered. Blood profiles were assayed before induction and after recovery of anesthesia. Heart and respiratory rates, rectal temperature, saturation of peripheral oxygen and mean arterial blood pressure were recorded. Heart rate increased significantly 1 to 5 minutes after induction of anesthesia in experimental groups (P < 0.05. Although mean arterial blood pressure decreased significantly from baseline, values remained above 60 mm Hg (P < 0.05. Respiratory rate decreased significantly in experimental groups, but remained higher in group 2 (P < 0.05. The lymphocyte count decreased significantly in group 1 (P < 0.05. The concentration of alkaline phosphatase in all rabbits, aspartate aminotransferase and gamma- glutamyl transferase in the first group and gamma-glutamyl transferase in the third group increased significantly (P < 0.05. Total bilirubin decreased significantly in group 2 (P < 0.05. All measured values remained within normal limits. Based on the least significant physiological, hematological and biochemical effects, the IO injection of propofol appears to be safe and suitable method of anesthesia in rabbits with limited vascular access.

  13. Bioavailability and pharmacokinetics of oral and injectable formulations of methadone after intravenous, oral, and intragastric administration in horses.

    Science.gov (United States)

    Linardi, Renata L; Stokes, Ashley M; Keowen, Michael L; Barker, Steven A; Hosgood, Giselle L; Short, Charles R

    2012-02-01

    To characterize the bioavailability and pharmacokinetics of oral and injectable formulations of methadone after IV, oral, and intragastric administration in horses. 6 healthy adult horses. Horses received single doses (each 0.15 mg/kg) of an oral formulation of methadone hydrochloride orally or intragastrically or an injectable formulation of the drug orally, intragastrically, or IV (5 experimental treatments/horse; 2-week washout period between each experimental treatment). A blood sample was collected from each horse before and at predetermined time points over a 360-minute period after each administration of the drug to determine serum drug concentration by use of gas chromatography-mass spectrometry analysis and to estimate pharmacokinetic parameters by use of a noncompartmental model. Horses were monitored for adverse effects. In treated horses, serum methadone concentrations were equivalent to or higher than the effective concentration range reported for humans, without induction of adverse effects. Oral pharmacokinetics in horses included a short half-life (approx 1 hour), high total body clearance corrected for bioavailability (5 to 8 mL/min/kg), and small apparent volume of distribution corrected for bioavailability (0.6 to 0.9 L/kg). The bioavailability of methadone administered orally was approximately 3 times that associated with intragastric administration. Absorption of methadone in the small intestine in horses appeared to be limited owing to the low bioavailability after intragastric administration. Better understanding of drug disposition, including absorption, could lead to a more appropriate choice of administration route that would enhance analgesia and minimize adverse effects in horses.

  14. Comparison of time to loss of consciousness and maintenance of anesthesia following intraosseous and intravenous administration of propofol in rabbits.

    Science.gov (United States)

    Mazaheri-Khameneh, Ramin; Sarrafzadeh-Rezaei, Farshid; Asri-Rezaei, Siamak; Dalir-Naghadeh, Bahram

    2012-07-01

    To compare time to loss of consciousness (LOC) and effective maintenance of anesthesia following intraosseous (IO) and IV administration of propofol in rabbits. Evaluation study. 24 New Zealand White rabbits. Rabbits were selected to receive IO (n = 6) or IV (6) bolus administration of 1% propofol (12.5 mg/kg [5.67 mg/lb]) only or an identical bolus of propofol IO (6) or IV (6) followed by a constant rate infusion (CRI; 1 mg/kg/min [0.45 mg/lb/min]) by the same route for 30 minutes. Physiologic variables were monitored at predetermined time points; time to LOC and durations of anesthesia and recovery were recorded. Following IO and IV bolus administration, mean time to LOC was 11.50 and 7.83 seconds, respectively; changes in heart rate, respiratory rate, oxygen saturation (as measured by pulse oximetry), and mean arterial blood pressure values were evident, but findings did not differ between groups. For the IO- and IV-CRI groups, propofol-associated changes in heart rate, oxygen saturation, and mean arterial blood pressure values were similar, and although mean arterial blood pressure decreased significantly from baseline, values remained > 60 mm Hg; respiratory rate decreased significantly during CRI in both groups, but remained higher in the IO-CRI group. Anesthesia and recovery time did not differ between the IO- and IV-CRI groups. In all evaluated aspects of anesthesia, IO administration of propofol was as effective as IV administration in rabbits. Results suggested that total IO anesthesia can be performed in rabbits with limited vascular access.

  15. 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.

  16. Intravenous administration of iodinated, non-ionic, low or isoosmolar contrast media: safety aspects; Intravenoese Anwendung von jodiertem, nichtionischem, nieder- bis isoosmolarem Kontrastmittel: Sicherheitsaspekte

    Energy Technology Data Exchange (ETDEWEB)

    Metz-Schimmerl, S.; Metz, V.; Schima, W.; Herold, C. [Universitaetsklinik fuer Radiodiagnostik und Ludwig Boltzmann-Institut fuer Klinische und Experimentelle Radiologie, Wien (Austria); Domanovits, H. [Universitaetsklinik fuer Notfallmedizin Wien, Wien (Austria)

    2002-01-01

    It iss the purpose of this review to provide information about the safe use of intravenously administered, iodinated, non-ionic, low or isoosmolar contrast media for radiological examinations, how to avoid adverse events, and how to react professionally in case of an anaphylactic reaction. Methods of prophylaxis and therapy for anaphylactic and chemotoxic effects of contrast media administration as well as absolute and relative contraindications are discussed. Medico-legal considerations of contrast agent administration, informed consent of patients, and methods of risk management for undesired contrast media reactions are considered in this article. Establishment of administration standards for contrast media is of tremendous importance to standardize radiological procedures. This basic radiological documentation is part of the institutional and individual legal safety management. (orig.) [German] Ziel dieses Artikels ist es, Kenntnisse zur sicheren Anwendung von intravenoes applizierten, jodierten, nichtionischen, nieder- bis isoosmolaren Roentgen-Kontrastmitteln zu vermitteln, um bei deren Verwendung unerwuenschte Wirkungen zu vermeiden oder im Falle eines anaphylaktischen Kontrastmittelzwischenfalls rasch und effektiv zu handeln. Neben Methoden der Verhuetung und Behandlung anaphylaktischer und chemotoxischer Wirkungen der Kontrastmittelgabe werden Einschraenkungen der Anwendung bei unterschiedlichen klinischen Bildern eroertert. Rechtliche Ueberlegungen zur Kontrastmittelanwendung, das Aufklaerungsgespraech und Praeventivmassnahmen zum Risiko-Management unerwuenschter Kontrastmittelwirkungen sind beruecksichtigt. Die Festlegung von Anwendungstandards fuer Kontrastmittel dient der Normierung medizinischen Vorgehens. Eine solche radiologische Basisdokumentation ist teil der institutionellen und individuellen rechtlichen Absicherung. (orig.)

  17. Accumulation of radioactivity in rat brain and peripheral tissues including salivary gland after intravenous administration of 14C-D-aspartic acid

    International Nuclear Information System (INIS)

    Imai, Kazuhiro; Fukushima, Takeshi; Santa, Tomofumi; Homma, Hiroshi; Sugihara, Juko; Kodama, Hirohiko; Yoshikawa, Masayoshi.

    1997-01-01

    After the intravenous administration of 14 C-D-aspartic acid (Asp) into Sprague-Dawley rats (male, 7-week-old), the distribution and elimination of radioactivity was investigated by the whole body autoradiography. High radioactivities were detected in pineal gland, pituitary gland and salivary gland at 30 min after administration. The other tissues detected were liver, lung, adrenal gland, pancreas and spleen where D-Asp was reported to occur naturally. After 24 hr, the radioactivities were still detected at high levels in the pineal, pituitary and salivary glands. The data suggested the natural occurrence of D-Asp in salivary gland. After careful examination utilizing fluorescent derivatization and chiral separation by high-performance liquid chromatography, the presence of D-Asp was, for the first time, demonstrated in salivary gland in situ, the concentration of which was 7.85 ± 1.0 nmol/g. The administration of 14 C-L-Asp was also carried out. The data suggested that D-Asp in the circulating blood is one of the sources of the tissue D-Asp. (author)

  18. The effect of intravenous dextrose administration for prevention of post-operative nausea and vomiting after laparoscopic cholecystectomy: A double-blind, randomised controlled trial.

    Science.gov (United States)

    Firouzian, Abolfazl; Kiasari, Alieh Zamani; Godazandeh, Gholamali; Baradari, Afshin Gholipour; Alipour, Abbas; Taheri, Arman; Emami Zeydi, Amir; Montazemi, Maryam

    2017-10-01

    Post-operative nausea and vomiting (PONV) is a common and distressing complication after laparoscopic cholecystectomy (LC). The aim of this study was to evaluate the effect of intravenous (IV) dextrose administration for the prophylaxis of PONV after LC. In a double-blind, randomised controlled trial, a total of 150 female patients who were scheduled for elective LC were randomly assigned into two groups (A and B). Thirty minutes before induction of anaesthesia, patients received an infusion of 500 cc lactated Ringer's solution (Group A) and 5% dextrose in lactated Ringer's solution (Group B) and over a period of 30 min. All patients rated their nausea and vomiting intensity using the verbal rating scale immediately at post-anaesthesia care unit (PACU) arrival; 30, 60, 90 and 120 min after arriving at the PACU and 6, 12 and 24 h after surgery. There was a statistically significant time trend and group effect along with significant differences in time/group interaction effect in both groups for nausea and vomiting scores ( P Dextrose administration reduced the odds of vomiting events compared to placebo (estimate: -0.87, odds ratio = 0.42, 95% confidence interval: 0.28-0.64). Administration of IV dextrose before anaesthesia induction may be recommended as an effective, and safe method for the prophylaxis of PONV after LC.

  19. Impact of Solutol HS 15 on the pharmacokinetic behavior of midazolam upon intravenous administration to male Wistar rats.

    Science.gov (United States)

    Bittner, Beate; González, Roberto Carlos Bravo; Isel, Hughes; Flament, Christophe

    2003-07-01

    The pharmacokinetic profile of midazolam (MDZ) and its major metabolites 1'-OH-midazolam (1'OH-MDZ) and 4-OH-midazolam (4OH-MDZ) was investigated in rats. MDZ was administered intravenously at 5 mg/kg either in the absence (NaCl 0.9%, control group) or in the presence of the surfactant Solutol HS 15, a weak inhibitor of cytochrome P450 3A (CYP3A) activity in vitro (Solutol HS 15-treated group). It was found that the pharmacokinetic profiles of MDZ, 1'OH-MDZ and 4OH MDZ did not differ significantly in the two dosing vehicles (P values above 0.2). MDZ exhibited a high plasma clearance (Cl) of 79 and 92 ml/min/kg (corresponding to a blood Cl of 64 and 75 ml/min/kg), a high volume of distribution (V(d)) of 4.0 and 3.6 l/kg, and an area under the plasma concentration-time curve (AUC(t0-tinf)) of 1062 and 932 h.ng/ml in the control group and in the Solutol HS 15-treated group, respectively. The amount of MDZ excreted unchanged into urine was below 0.01% with both dosing vehicles. AUC(t0-tinf) in the control group was 12.3 h.ng/ml for 1'OH-MDZ and 38.8 h.ng/ml 4OH-MDZ. In the Solutol HS 15-treated group, AUC(t0-tinf) was 14 h.ng/ml for 1'OH-MDZ and 35.4 h.ng/ml for 4OH-MDZ. The metabolite concentrations excreted into urine were below the limit of quantification. In the rat, MDZ has a high blood clearance that is limited by liver blood flow. Therefore, weak CYP3A inhibitors like Solutol HS 15 are not likely to affect the hepatic blood clearance of MDZ in vivo.

  20. 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.

  1. Safety and efficacy of intravenous administration for tranexamic acid-induced emesis in dogs with accidental ingestion of foreign substances.

    Science.gov (United States)

    Orito, Kensuke; Kawarai-Shimamura, Asako; Ogawa, Atsushi; Nakamura, Atsushi

    2017-12-22

    A prospective observational study was performed in canine clinical medicine to evaluate the emetic action and adverse effects of tranexamic acid. Veterinarians treated 137 dogs with a single dose of tranexamic acid (50 mg/kg, IV) after accidental ingestion of foreign substances. If needed, a second (median, 50 mg/kg; range, 20-50 mg/kg, IV) or third dose (median, 50 mg/kg; range, 25-50 mg/kg, IV) was administered. Tranexamic acid induced emesis in 116 of 137 (84.7%) dogs. Median time to onset of emesis was 116.5 sec (range, 26-370 sec), median duration of emesis was 151.5 sec (range, 30-780 sec), and median number of emesis episodes was 2 (range, 1-8). Second and third administrations of tranexamic acid induced emesis in 64.7 and 66.7% of dogs, respectively. In total, IV administration of tranexamic acid successfully induced emesis in 129 of 137 (94.2%) dogs. Adverse effects included a tonic-clonic convulsion and hemostatic disorder in two different dogs, both of which recovered after receiving medical care. Tranexamic acid induced emesis in most dogs following a single-dose. When a single dose was not sufficient, an additional dosage effectively induced emesis. Overall, adverse effects were considered low and self-limiting.

  2. The relationship of intravenous dextrose administration during emergence from anesthesia to postoperative nausea and vomiting: a randomized controlled trial.

    Science.gov (United States)

    Patel, Parul; Meineke, Minhthy N; Rasmussen, Thomas; Anderson, Donald L; Brown, Jennifer; Siddighi, Sam; Applegate, Richard L

    2013-07-01

    Postoperative nausea and vomiting (PONV) may occur despite antiemetic prophylaxis and is associated with unanticipated hospital admission, financial impact, and patient dissatisfaction. Previous studies have shown variable impact of IV dextrose on PONV. We sought to determine the relationship of IV dextrose administered during emergence from anesthesia to PONV. This was a prospective, double-blind randomized placebo-controlled trial. Adult female ASA physical status I and II nondiabetic patients scheduled for outpatient gynecologic, urologic, or breast surgery were randomly assigned to infusion of 250 mL lactated Ringer's solution (group P; n = 75) or dextrose 5% in lactated Ringer's solution (group D; n = 87) over 2 hours beginning with surgical closing. Blood glucose was determined using a point-of-care device before transfer to the operating room, in the operating room immediately before study fluid infusion, and in the recovery room after study fluid infusion. No antiemetics were given before arrival in the recovery room. PONV scores were recorded at 0, 30, 60, and 120 minutes and 24 hours after arrival in the recovery room. Medication administration was recorded. Data from 162 patients with normal baseline blood glucose were analyzed. There were no significant intergroup differences in demographics, history of PONV, or tobacco use. There was no significant intergroup difference in PONV during the first 2 hours after anesthesia (group D 52.9% vs group P 46.7%; difference, 6.2%; 95% confidence interval [CI], -9.2% to 21.6%; P = 0.43). Patients in groups D or P who developed PONV within 2 hours of anesthesia had similar number of severity scores ≥1 during recovery stay (1.5 vs 1.0; difference, 0; 95% CI, 0%-0%; P = 0.93); and similar proportions of: PONV onset within 30 minutes of recovery room arrival (65.2% vs 57.1%; difference, 8.1%; 95% CI, -13.1% to 28.8%; P = 0.46); more than 1 dose of antiemetic medication (56.5% vs 62.9%; difference, 6.3%; 95% CI, -26

  3. Effect of intravenous administration of D-lysergic acid diethylamide on initiation of protein synthesis in a cell-free system derived from brain.

    Science.gov (United States)

    Cosgrove, J W; Brown, I R

    1984-05-01

    An initiating cell-free protein synthesis system derived from brain was utilized to demonstrate that the intravenous injection of D-lysergic acid diethylamide (LSD) to rabbits resulted in a lesion at the initiation stage of brain protein synthesis. Three inhibitors of initiation, edeine, poly(I), and aurintricarboxylic acid were used to demonstrate a reduction in initiation-dependent amino acid incorporation in the brain cell-free system. One hour after LSD injection, there was also a measurable decrease in the formation of 40S and 80S initiation complexes in vitro, using either [35S]methionine or [35S]Met-tRNAf. Analysis of the methionine pool size after LSD administration indicated there was no change in methionine levels. Analysis of the formation of initiation complexes in the brain cell-free protein synthesis system prepared 6 h after LSD administration indicated that there was a return to control levels at this time. The effects of LSD on steps in the initiation process are thus reversible.

  4. Intravenous administration of the adeno-associated virus-PHP.B capsid fails to upregulate transduction efficiency in the marmoset brain.

    Science.gov (United States)

    Matsuzaki, Yasunori; Konno, Ayumu; Mochizuki, Ryuta; Shinohara, Yoichiro; Nitta, Keisuke; Okada, Yukihiro; Hirai, Hirokazu

    2018-02-05

    Intravenous administration of adeno-associated virus (AAV)-PHP.B, a capsid variant of AAV9 containing seven amino acid insertions, results in a greater permeability of the blood brain barrier (BBB) than standard AAV9 in mice, leading to highly efficient and global transduction of the central nervous system (CNS). The present study aimed to examine whether the enhanced BBB penetrance of AAV-PHP.B observed in mice also occurs in non-human primates. Thus, a young adult (age, 1.6 years) and an old adult (age, 7.2 years) marmoset received an intravenous injection of AAV-PHP.B expressing enhanced green fluorescent protein (EGFP) under the control of the constitutive CBh promoter (a hybrid of cytomegalovirus early enhancer and chicken β-actin promoter). Age-matched control marmosets were treated with standard AAV9-capsid vectors. The animals were sacrificed 6 weeks after the viral injection. Based on the results, only limited transduction of neurons (0-2%) and astrocytes (0.1-2.5%) was observed in both AAV-PHP.B- and AAV9-treated marmosets. One noticeable difference between AAV-PHP.B and AAV9 was the marked transduction of the peripheral dorsal root ganglia neurons. Indeed, the soma and axons in the projection from the spinal cord to the nucleus cuneatus in the medulla oblongata were strongly labeled with EGFP by AAV-PHP.B. Thus, except for the peripheral dorsal root ganglia neurons, the AAV-PHP.B transduction efficiency in the CNS of marmosets was comparable to that of AAV9 vectors. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Shenghao Wu

    2015-01-01

    Full Text Available Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM patients with the therapy of subcutaneous (subQ administration of bortezomib and dexamethasone plus thalidomide (VTD regimen. Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group.The efficacy and safety of two groups were analyzed retrospectively. Results. The overall remission (OR after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05. No significant differences in time to 1-year estimate of overall survival (72% versus 75%, P=0.848 and progression-free survival (median 22 months versus 25 months; P=0.725 between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50% than VTD group (80%, P=0.015. Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

  6. Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine.

    Science.gov (United States)

    Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah; Ettenberg, Aaron

    2011-04-01

    Evidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers. The current study was therefore devised to test the hypothesis that differences in the animals' responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of prior cocaine and heroin runway self-administration. Rats ran a straight alley for single intravenous injections of either heroin (0.1 mg/kg/inj) or cocaine (1.0 mg/kg/inj) each paired with a distinct olfactory cue. Animals experienced 15 trials with each drug reinforcer in a counterbalanced manner. Start latencies, run times, and retreat behaviors (a form of approach-avoidance conflict) provided behavioral indices of the subjects' motivation to seek the reinforcer on each trial. Responsiveness to each drug-paired cue was assessed after 7, 14, or 21 days of non-reinforced extinction trials. Other animals underwent conditioned place preference (CPP) testing to ensure that the two drug reinforcers were capable of producing drug-cue associations. While both drugs produced comparable CPPs, heroin served as a stronger incentive stimulus in the runway as evidenced by faster start and run times and fewer retreats. In contrast, cocaine- but not heroin-paired cues produced increases in drug-seeking behavior during subsequent extinction trials. The subjects' responsiveness to drug-paired cues during extinction was not predicted by differences in the motivation to seek heroin versus cocaine during prior drug self-administration.

  7. NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

    Science.gov (United States)

    Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

    2009-01-01

    Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug.

  8. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

    Directory of Open Access Journals (Sweden)

    Tayra Judith

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL staining. Results Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. Conclusions Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

  9. Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

    International Nuclear Information System (INIS)

    Kamendi, Harriet; Zhou, Ying; Crosby, Meredith; Keirstead, Natalie; Snow, Debra; Bentley, Patricia; Patel, Nilaben; Barthlow, Herbert; Luo, Wenli; Dragan, Yvonne; Bialecki, Russell

    2015-01-01

    Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalized by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.

  10. Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kamendi, Harriet, E-mail: harriet_kamendi@kandih.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Zhou, Ying, E-mail: yingzhou526@gmail.com [Oncology Innovative Medicines and Early Development, AstraZeneca, Waltham, MA 02451 (United States); Crosby, Meredith, E-mail: Meredith.crosby@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Keirstead, Natalie, E-mail: Nkeirstead@alnylam.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Snow, Debra, E-mail: Debra.snow@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Bentley, Patricia, E-mail: patricia.bentley@abbvie.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Patel, Nilaben, E-mail: patelnilaben@yahoo.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Barthlow, Herbert, E-mail: Herbert.barthlow@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Luo, Wenli, E-mail: Wenli.luo@astrazeneca.com [Discovery Sciences, Innovative Medicines, AstraZeneca, Waltham, MA 02451 (United States); Dragan, Yvonne, E-mail: Yvonne.P.Dragan@takeda.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Bialecki, Russell, E-mail: russell.bialecki@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States)

    2015-12-15

    Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalized by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.

  11. 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.

  12. The normalized administration of hybrid operating room: its practical application in managing multiple injuries

    International Nuclear Information System (INIS)

    Li Xue; Zhang Weiguo; Zhang Lianyang; Chen Tingjing; Chen Jinhua

    2011-01-01

    Objective: Through carrying out the normalized administration of hybrid operating room the application of the operating room is expanded to the performing of multiple injuries, and, in this way, the operative management become standardized and programmed, the cooperation and efficiency of hybrid operations for multiple injuries are improved and the surgeries can be ensured. Methods: According to the characteristics of hybrid interventional operation for multiple injuries, the basic construction of the hybrid operating room improved, the hybrid operation team was organized, and the administrative system as well as the working program were established. The green channel for rescuing patients with multiple injuries was set up. The cooperative behavior during interventional treatment for multiple injuries was specified. Results: The coordination and working efficiency of physicians, nurses, technicians and anesthetists were well improved. The qualified rate of lamina flow administration reached 100%. The success rate of the rescue of multiple injuries was increased. Conclusion: As one-stop complex interventional operation for multiple injuries is a new technique, there is no integrated administration system. Therefore, the establishment of standardized management of one-stop complex interventional operation is of great significance in guiding clinical practice. (authors)

  13. A novel double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]tofogliflozin after oral administration and concomitant intravenous microdose administration of [13C]tofogliflozin in humans.

    Science.gov (United States)

    Schwab, Dietmar; Portron, Agnes; Backholer, Zoe; Lausecker, Berthold; Kawashima, Kosuke

    2013-06-01

    Human mass balance studies and the assessment of absolute oral bioavailability (F) are usually assessed in separate studies. Intravenous microdose administration of an isotope tracer concomitant to an unlabeled oral dose is an emerging technique to assess F. We report a novel double-tracer approach implemented for tofogliflozin combining oral administration of a radiolabel tracer with concomitant intravenous administration of a stable isotope tracer. Tofogliflozin is a potent and selective sodium/glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus currently in clinical development. The objectives of the present study were to assess the systemic exposure of major circulating metabolites, excretion balance, F and contribution of renal clearance (CLR) to total clearance (CL) of tofogliflozin in healthy subjects within one study applying a novel double-tracer technique. Six healthy male subjects received 20 mg [(12)C/(14)C]tofogliflozin (3.73 MBq) orally and a concomitant microdose of 0.1 mg [(13)C]tofogliflozin intravenously. Pharmacokinetics of tofogliflozin were determined for the oral and intravenous route; the pharmacokinetics of the metabolites M1 and M5 were determined for the oral route. Quantification of [(12)C]tofogliflozin in plasma and urine and [(13)C]tofogliflozin in plasma was performed by selective LC-MS/MS methods. For the pre-selected metabolites of tofogliflozin, M1 and M5, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to plasma and urine samples. Total radioactivity was assessed in plasma, urine and feces. Pharmacokinetic analysis was conducted by non-compartmental methods. The pharmacokinetics of tofogliflozin in healthy subjects were characterized by an F of 97.5 ± 12.3 %, CL of 10.0 ± 1.3 l/h and volume of distribution at steady-state (V(ss)) of 50.6 ± 6.7 l. The main route of elimination of total drug-related material was by excretion into urine (77.0 ± 4.1 % of the dose). The

  14. A study of pharmacokinetic interactions among co-existing ingredients in Viscum coloratum after intravenous administration of three different preparations to rats.

    Science.gov (United States)

    Ma, Yuying; Fan, Ronghua; Duan, Mengmeng; Yu, Zhiguo; Zhao, Yunli

    2015-01-01

    Viscum coloratum (Komar) Nakai, known as Hujisheng in china, has been widely used as a herb medicine to treat a variety of diseases, including cardiovascular diseases, cancer, hypertension, hepatitis and hemorrhage. The aim was to investigate pharmacokinetic interactions among co-existing ingredients in V. coloratum after intravenous administration of three different preparations (four monomer solutions, the mixture of them and Viscum coloratum extracts) to rats. After protein precipitation pretreatment with plasma samples, high performance liquid chromatographic methods were developed and applied to quantitatively determinate the four components [syringin (Syri), homoeriodictyol-7-O-β-D-glycoside (Hedt-III), homoeriodictyol-7-O-β-D-apiose (1 → 2)-β-D-glycoside (Hedt-II) and homoeriodictyol-7-O-β-D-apiosiyl-(1 → 5)-β-D-apiosyl-(1 → 2)-β-D-glycoside (Hedt-I)]. The pharmacokinetic parameters (Area under the curve [AUC(0-t)], AUC(0-∞), t 1/2) were calculated using DAS 2.1 software (Chinese Pharmacological Society, Shanghai, China) and compared statistically by One-way analysis of variance using SPSS software (18.0, Chicago, IL, USA) with P dialectic view in the research and development processes.

  15. Accidents and Incidents Related to Intravenous Drug Administration: A Pre-Post Study Following Implementation of Smart Pumps in a Teaching Hospital.

    Science.gov (United States)

    Guérin, Aurélie; Tourel, Julien; Delage, Emmanuelle; Duval, Stéphanie; David, Marie-Johanne; Lebel, Denis; Bussières, Jean-François

    2015-08-01

    Smart pumps are expected to prevent and reduce medication errors. The implementation of smart pumps requires a significant effort and collaboration of physicians, nurses, pharmacists, and other stakeholders. The main objective of this study was to evaluate the impact of new smart pumps on reported drug-related accidents and incidents (AIs). This is a descriptive retrospective pre-post study conducted at a women's and pediatric hospital with 500 beds. A strong multidisciplinary team (nurse, pharmacist, pharmacy resident, physician, biomedical technician, information technology technician, patient safety officer, manager) was involved in the planning, implementation, and monitoring technology implementation. A total of 1045 smart pumps were implemented in 2011 in our hospital. The reported number of AIs related to intravenous drug administration (AIIV) before and after the implementation of 1045 smart pumps were collected. A total of 2911 AI events related to medications, devices, and equipment were self-reported by clinical staff in the pre-phase (Y0), 3523 in the post-phase (Y1), and 2788 in the post-phase (Y2). The total AIIV increased from 1432 in Y0 to 1834 in Y1 and decreased to 1389 in Y2. We observed no risk reduction associated with the implementation of smart pumps in a 500 bed mother-child hospital. Further studies are required to explore the details of the potential risk reduction associated with the use of smart pumps.

  16. Effect of intradialytic intravenous administration of omega-3 fatty acids on nutritional status and inflammatory response in hemodialysis patients: a pilot study.

    Science.gov (United States)

    Szklarek-Kubicka, Magdalena; Fijałkowska-Morawska, Jolanta; Zaremba-Drobnik, Danuta; Uciński, Andrzej; Czekalski, Stanisław; Nowicki, Michał

    2009-11-01

    Because omega-3 polyunsaturated fatty acids (PUFAs) may have anti-inflammatory properties, we tested the hypothesis that intradialytic, intravenous omega-3 PUFA treatment, combined with dietary supplementation, can modify the inflammatory response to dialysis, and influence the nutritional status of hemodialysis (HD) patients. Twenty HD patients with serum albumin at HD sessions. Body mass index (BMI), serum albumin, transferrin, and lipids were measured before and after treatment. Serum interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) levels were determined before and after the HD session at baseline and after 4 weeks of treatment. No adverse events were evident during the study. There were no significant changes in BMI, serum albumin, transferin, total and low-density lipoprotein cholesterol, and triglycerides. Predialysis hsCRP and IL-6 did not change. There was a significant increase in hsCRP (P=.01) and a tendency of IL-6 concentration to increase during the HD session before treatment (P=.067). In contrast, neither hsCRP (P=.21) nor IL-6 (P=.26) changed during the final HD session. Neither urea reduction ratio nor Kt/V changed significantly during the study, but the normalized protein catabolic ratio increased after treatment (P=.003). Short-term parenteral administration of omega-3 PUFA is safe and well-tolerated by HD patients. The intervention does not significantly influence markers of inflammation or change the nutritional status of chronic HD patients, but it may attenuate the inflammatory response to HD sessions.

  17. Absolute bioavailability of evacetrapib in healthy subjects determined by simultaneous administration of oral evacetrapib and intravenous [13C8]‐evacetrapib as a tracer

    Science.gov (United States)

    Aburub, Aktham; Ward, Chris; Hinds, Chris; Czeskis, Boris; Ruterbories, Kenneth; Suico, Jeffrey G.; Royalty, Jane; Ortega, Demetrio; Pack, Brian W.; Begum, Syeda L.; Annes, William F.; Lin, Qun; Small, David S.

    2015-01-01

    This open‐label, single‐period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130‐mg evacetrapib oral dose and 4‐h intravenous (IV) infusion of 175 µg [13C8]‐evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [13C8]‐evacetrapib using high‐performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration‐time curve (AUC) from zero to infinity (AUC[0‐∞]) and to the last measureable concentration (AUC[0‐tlast]), were calculated. Bioavailability was calculated as the ratio of least‐squares geometric mean of dose‐normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2–47.6%) for AUC(0‐∞) and 44.3% (90% CI: 41.8–46.9%) for AUC(0‐tlast). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a 13C‐labeled IV microdose tracer at about 1/1000th the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability. PMID:26639670

  18. Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab.

    Science.gov (United States)

    Theodore-Oklota, Christina; Humphrey, Louise; Wiesner, Christof; Schnetzler, Gabriel; Hudgens, Stacie; Campbell, Alicyn

    2016-01-01

    A subcutaneous (SC) formulation of rituximab (MabThera ® /Rituxan ® ) has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ) was created to assess patients' perceptions and satisfaction with rituximab SC (RASQ-SC) or rituximab intravenous (RASQ-IV). We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma. Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability) was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ), using questionnaire data from the PrefMab (NCT01724021) and MabCute (NCT01461928) clinical studies. RASQ-IV demonstrated excellent coverage of concepts relevant to patients' (n=10) own treatment experiences and no new concepts were identified. Patients' expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as "RASQ: Physical Impacts" and "CTSQ: Feelings About Side Effects", "RASQ: Physical Impacts" and "CTSQ: Satisfaction With Therapy", and "RASQ: Satisfaction" and "CTSQ: Satisfaction With Therapy", achieved moderate-to-high correlations (>0.4) for convergent domains and <0.3 for divergent domains. This study supports the qualitative face and content validity and psychometric validity of RASQ-IV and RASQ-SC. Minor revisions were made to the questionnaires to enhance clarity and aid consistent reporting.

  19. Effects of intravenously administered yohimbine on antinociceptive, cardiorespiratory, and postural changes induced by epidural administration of detomidine hydrochloride solution to healthy mares.

    Science.gov (United States)

    Skarda, R T; Muir, W W

    1999-10-01

    To determine effects of i.v. administered yohimbine on perineal analgesia, cardiovascular and respiratory activity, and head and pelvic limb position in healthy mares following epidural administration of detomidine hydrochloride solution. 8 healthy mares. Each mare received detomidine hydrochloride (0.06 mg/kg of body weight), administered in the caudal epidural space, followed 61 minutes later by yohimbine (0.05 mg/kg; test) or sterile saline (0.9% NaCl) solution (control), administered i.v., in a randomized, crossover study design with > or = 2 weeks between treatments. Analgesia was determined by lack of sensory perception to electrical stimulation of perineal dermatomes and needle-prick stimulation of coccygeal to 15th thoracic dermatomes. Arterial pH, PaCO2, PaO2, heart and respiratory rates, rectal temperature, arterial blood pressure, and cardiac output were determined, and mares were observed for sweating and urination. Mean scores obtained for test and control groups were compared. Intravenously administered yohimbine significantly reduced mean scores of detomidine-induced perineal analgesia, head ptosis, changes in pelvic limb position, and sweating and diuresis; antagonized detomidine-induced decreases in heart rate and cardiac output; but did not affect detomidine-induced decrease in respiratory rate. Most effects of epidurally administered detomidine, except bradypnea, were antagonized by yohimbine, suggesting that detomidine may influence respiratory rate by mechanisms other than stimulation of alpha2-adrenoceptors, or that yohimbine induces respiratory depressant effects. Yohimbine may be an effective alpha2-adrenoceptor antagonist for all but respiratory depression following epidural administration of detomidine to mares.

  20. Effective multiple oral administration of reverse genetics engineered infectious bursal disease virus in mice in the presence of neutralizing antibodies.

    Science.gov (United States)

    Hornyák, Ákos; Lipinski, Kai S; Bakonyi, Tamás; Forgách, Petra; Horváth, Ernő; Farsang, Attila; Hedley, Susan J; Palya, Vilmos; Bakács, Tibor; Kovesdi, Imre

    2015-01-01

    Despite spectacular successes in hepatitis B and C therapies, severe hepatic impairment is still a major treatment problem. The clinically tested infectious bursal disease virus (IBDV) superinfection therapy promises an innovative, interferon-free solution to this great unmet need, provided that a consistent manufacturing process preventing mutations or reversions to virulent strains is obtained. To address safety concerns, a tissue culture adapted IBDV vaccine strain V903/78 was cloned into cDNA plasmids ensuring reproducible production of a reverse engineered virus R903/78. The therapeutic drug candidate was characterized by immunocytochemistry assay, virus particle determination and immunoblot analysis. The biodistribution and potential immunogenicity of the IBDV agent was determined in mice, which is not a natural host of this virus, by quantitative detection of IBDV RNA by a quantitative reverse transcriptase-polymerase chain reaction and virus neutralization test, respectively. Several human cell lines supported IBDV propagation in the absence of visible cytopathic effect. The virus was stable from pH 8 to pH 6 and demonstrated significant resistance to low pH and also proved to be highly resistant to high temperatures. No pathological effects were observed in mice. Single and multiple oral administration of IBDV elicited antibodies with neutralizing activities in vitro. Repeat oral administration of R903/78 was successful despite the presence of neutralizing antibodies. Single oral and intravenous administration indicated that IBDV does not replicate in mammalian liver alleviating some safety related concerns. These data supports the development of an orally delivered anti-hepatitis B virus/ anti-hepatitis C virus viral agent for human use. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of ceftiofur after a single intravenous, subcutaneous and subcutaneous-LA administration in lactating goats.

    Science.gov (United States)

    Fernández-Varón, Emilio; Cárceles-García, Carlos; Serrano-Rodríguez, Juan Manuel; Cárceles-Rodríguez, Carlos M

    2016-10-13

    Bacterial pneumonia in goats is usually caused by Mannheimia haemolytica and Pasteurella multocida. Another important infection disease in lactating goats is intramammary infection producing mastitis, usually associated with coagulase-negative Staphylococcus spp. However, treatment of bacterial pneumonia in goats not affected by mastitis problems should be restricted to antimicrobials with scant penetration to milk in order to avoid long withdrawal times. Ceftiofur is a third-generation cephalosporin antimicrobial with activity against various gram-positive and gram-negative, aerobic and anaerobic bacteria encountered by domestic animals. The objectives of the present study were to establish the serum concentration-time profile for ceftiofur in lactating goats after intravenous, subcutaneous and a SC-long-acting ceftiofur formulation; to determine ceftiofur penetration into milk; to determine in vitro and ex vivo activity of ceftiofur establishing MIC, MBC, MPC and time-kill profiles against field strains of M. haemolytica and finally to calculate the main surrogate markers of efficacy. The pharmacokinetics studies revealed an optimal PK properties for the SC-LA formulation tested. Ceftiofur was well absorbed following SC and SC-LA administration, with absolute bioavailabilities (F) of 85.16 and 84.43 %, respectively. After ceftiofur analysis from milk samples, no concentrations were found at any sampling time. The MIC, MBC and MPC data of ceftiofur against five M. haemolytica strains isolated from goats affected by pneumonia were tested showing excelent sensitivity of ceftiofur against this pathogen. For PK-PD analysis, ratios were calculated suggesting a high level of bacterial kill against the five strains of M. haemolytica tested. The systemic ceftiofur exposure achieved in lactating goats following IV, SC and especially with the SC-LA administration is consistent with the predicted PK-PD ratios needed for a positive therapeutic outcome for M. haemolytica

  2. Chronic variable stress and intravenous methamphetamine self-administration – role of individual differences in behavioral and physiological reactivity to novelty

    Science.gov (United States)

    Taylor, S.B.; Watterson, L.R.; Kufahl, P.R.; Nemirovsky, N.E.; Tomek, S.E.; Conrad, C.D.; Olive, M.F.

    2016-01-01

    Stress is a contributing factor to the development and maintenance of addiction in humans. However, few studies have shown that stress potentiates the rewarding and/or reinforcing effects of methamphetamine in rodent models of addiction. The present study assessed the effects of exposure to 14 days of chronic variable stress (CVS), or no stress as a control (CON), on the rewarding and reinforcing effects of methamphetamine in adult rats using the conditioned place preference (Experiment 1) and intravenous self-administration (Experiment 2) paradigms. In Experiment 2, we also assessed individual differences in open field locomotor activity, anxiety-like behavior in the elevated plus maze (EPM), and physiological responses to a novel environment as possible predictors of methamphetamine intake patterns. Exposure to CVS for 14 days did not affect overall measures of methamphetamine conditioned reward or reinforcement. However, analyses of individual differences and direct vs. indirect effects revealed that rats exhibiting high physiological reactivity and locomotor activity in the EPM and open field tests self-administered more methamphetamine and reached higher breakpoints for drug reinforcement than rats exhibiting low reactivity. In addition, CVS exposure significantly increased the proportion of rats that exhibited high reactivity, and high reactivity was significantly correlated with increased levels of methamphetamine intake. These findings suggest that individual differences in physiological and locomotor reactivity to novel environments, as well as their interactions with stress history, predict patterns of drug intake in rodent models of methamphetamine addiction. Such predictors may eventually inform future strategies for implementing individualized treatment strategies for amphetamine use disorders. PMID:27163191

  3. Long-Term Impact of Implementation of a Stroke Protocol on Door-to-Needle Time in the Administration of Intravenous Tissue Plasminogen Activator.

    Science.gov (United States)

    Hillen, Machteld E; He, Wenzhuan; Al-Qudah, Zaid; Wang, Weizhen; Hidalgo, Andrea; Walia, Jessy

    2017-07-01

    This study aims to evaluate the effectiveness of implementing a stroke protocol (SP) in improving door-to-needle time (DTNT) and door-to-computed tomography (DTCT) time from 2010 to 2014. Published data from the Get With The Guidelines-Stroke (GWTGS) participating hospitals showed that median DTNT = 75 minutes with 26.6% of the patients achieving the recommended DTNT of 60 minutes or less. Implementation of an SP, which specifies the role of nurses, physicians, and technicians during acute stroke evaluation, can improve DTNT. This longitudinal quality assurance study was designed to compare the DTNT and the DTCT time pre- and post implementation of an SP in our hospital. Patients' data before (2009-2010) and after (2010-2014) the implementation of an SP were collected each year during the same 6-month period and compared using statistical software SPSS 20.0 for Windows (SPSS Inc., Chicago, IL). Although our DTNT did not significantly improve over the years, the median DTNT (59 minutes) was much less than the reported 75 minutes of GWTGS hospitals. Our DTCT time diminished from 20.6 minutes in 2009 to 15.9 minutes in 2014. The percentage of patients with a DTNT of 1 hour or less did not differ among all years (P = .296) and was 55.8%. Our study suggests that our performance in evaluating acute ischemic stroke patients within the American Heart Association/American Stroke Association suggested time window is reachable for prolonged periods of time. Continuous monitoring and education of all players involved are crucial to ensure best possible outcomes in the timely administration of intravenous tissue plasminogen activator. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  4. Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

    Science.gov (United States)

    Nemec, Ursula; Nemec, Stefan F; Novotny, Clemens; Weber, Michael; Czerny, Christian; Krestan, Christian R

    2012-06-01

    To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

  5. Combined intravenous, topical and oral tranexamic acid administration in total knee replacement: Evaluation of safety in patients with previous thromboembolism and effect on hemoglobin level and transfusion rate.

    Science.gov (United States)

    Jansen, Joris A; Lameijer, Joost R C; Snoeker, Barbara A M

    2017-10-01

    The aims of this study were to investigate the safety of combined intravenous, oral and topical tranexamic acid (TXA) in primary total knee replacement. We assessed dose-related efficacy on hemoglobin level, transfusion, length of stay and thromboembolic complications. In addition, TXA safety in patients with previous history of thromboembolism >12months ago was monitored specifically. From January 2013 until January 2016, 922 patients were included who received TXA after primary total knee replacement. Patients without TXA administration or with thromboembolic events 10-25mg/kg and >25-50mg/kg. Between the three TXA groups no significant difference was found in thromboembolic complications (deep venous thrombosis (DVT) and pulmonary embolism (PE)), wound leakage and transfusion rate. For patients with DVT or PE in their history >12months ago specifically, no more complications were noted in higher-TXA-dosage groups compared to the low-dosage group. Length of stay was shorter in the highest-TXA-dosage group compared with lower-dosage groups (median two vs three days). With high TXA dose a smaller difference between pre- and postoperative Hb was found: the >25-50mg/kg TXA group had a 0.419mmol/l smaller decrease in postoperative hemoglobin compared to the lowest-dosage group (Ptopical TXA is effective in knee replacement and can safely be given to patients with a thromboembolic history >12months ago. High dosage (>25-50mg/kg) TXA resulted in the smallest decrease in postoperative hemoglobin. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Elucidation of Arctigenin Pharmacokinetics and Tissue Distribution after Intravenous, Oral, Hypodermic and Sublingual Administration in Rats and Beagle Dogs: Integration of In Vitro and In Vivo Findings

    Directory of Open Access Journals (Sweden)

    Jie Li

    2017-06-01

    Full Text Available Although arctigenin (AG has diverse bioactivities, such as anti-oxidant, anti-inflammatory, anti-cancer, immunoregulatory and neuroprotective activities, its pharmacokinetics have not been systematically evaluated. The purpose of this work was to identify the pharmacokinetic properties of AG via various experiments in vivo and in vitro. In this research, rats and beagle dogs were used to investigate the PK (pharmacokinetics, PK profiles of AG with different drug-delivery manners, including intravenous (i.v, hypodermic injection (i.h, and sublingual (s.l administration. The data shows that AG exhibited a strong absorption capacity in both rats and beagle dogs (absorption rate < 1 h, a high absorption degree (absolute bioavailability > 100%, and a strong elimination ability (t1/2 < 2 h. The tissue distributions of AG at different time points after i.h showed that the distribution of AG in rat tissues is rapid (2.5 h to reach the peak and wide (detectable in almost all tissues and organs. The AG concentration in the intestine was the highest, followed by that in the heart, liver, pancreas, and kidney. In vitro, AG were incubated with human, monkey, beagle dog and rat liver microsomes. The concentrations of AG were detected by UPLC-MS/MS at different time points (from 0 min to 90 min. The percentages of AG remaining in four species’ liver microsomes were human (62 ± 6.36% > beagle dog (25.9 ± 3.24% > rat (15.7 ± 9% > monkey (3.69 ± 0.12%. This systematic investigation of pharmacokinetic profiles of arctigenin (AG in vivo and in vitro is worthy of further exploration.

  7. Very-short-term perioperative intravenous iron administration and postoperative outcome in major orthopedic surgery: a pooled analysis of observational data from 2547 patients.

    Science.gov (United States)

    Muñoz, Manuel; Gómez-Ramírez, Susana; Cuenca, Jorge; García-Erce, José Antonio; Iglesias-Aparicio, Daniel; Haman-Alcober, Sami; Ariza, Daniel; Naveira, Enrique

    2014-02-01

    Postoperative nosocomial infection (PNI) is a severe complication in surgical patients. Known risk factors of PNI such as allogeneic blood transfusions (ABTs), anemia, and iron deficiency are manageable with perioperative intravenous (IV) iron therapy. To address potential concerns about IV iron and the risk of PNI, we studied a large series of orthopedic surgical patients for possible relations between IV iron, ABT, and PNI. Pooled data on ABT, PNI, 30-day mortality, and length of hospital stay (LHS) from 2547 patients undergoing elective lower-limb arthroplasty (n = 1186) or hip fracture repair (n = 1361) were compared between patients who received either very-short-term perioperative IV iron (200-600 mg; n = 1538), with or without recombinant human erythropoietin (rHuEPO; 40,000 IU), or standard treatment (n = 1009). Compared to standard therapy, perioperative IV iron reduced rates of ABT (32.4% vs. 48.8%; p = 0.001), PNI (10.7% vs. 26.9%; p = 0.001), and 30-day mortality (4.8% vs. 9.4%; p = 0.003) and the LHS (11.9 days vs. 13.4 days; p = 0.001) in hip fracture patients. These benefits were observed in both transfused and nontransfused patients. Also in elective arthroplasty, IV iron reduced ABT rates (8.9% vs. 30.1%; p = 0.001) and LHS (8.4 days vs.10.7 days; p = 0.001), without differences in PNI rates (2.8% vs. 3.7%; p = 0.417), and there was no 30-day mortality. Despite known limitations of pooled observational analyses, these results suggest that very-short-term perioperative administration of IV iron, with or without rHuEPO, in major lower limb orthopedic procedures is associated with reduced ABT rates and LHS, without increasing postoperative morbidity or mortality. © 2013 American Association of Blood Banks.

  8. Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab

    Directory of Open Access Journals (Sweden)

    Theodore-Oklota C

    2016-09-01

    Full Text Available Christina Theodore-Oklota,1 Louise Humphrey,2 Christof Wiesner,1 Gabriel Schnetzler,3 Stacie Hudgens,4 Alicyn Campbell1 1Genentech, South San Francisco, CA, USA; 2Adelphi Values, Macclesfield, Cheshire, UK; 3F. Hoffmann La-Roche Ltd, Basel, Switzerland; 4Clinical Outcomes Solutions, Tucson, AZ, USA Background: A subcutaneous (SC formulation of rituximab (MabThera®/Rituxan® has been developed that could reduce administration time and improve patient satisfaction with treatment. The Rituximab Administration Satisfaction Questionnaire (RASQ was created to assess patients’ perceptions and satisfaction with rituximab SC (RASQ-SC or rituximab intravenous (RASQ-IV. We assessed the content validity and psychometric properties of RASQ in patients with non-Hodgkin lymphoma.Methods: Face and content validity of RASQ-SC and RASQ-IV were qualitatively assessed using 60-minute combined concept elicitation and cognitive debriefing interviews. Psychometric validation of RASQ (item performance and reliability was assessed quantitatively against the established Cancer Therapy Satisfaction Questionnaire (CTSQ, using questionnaire data from the PrefMab (NCT01724021 and MabCute (NCT01461928 clinical studies.Results: RASQ-IV demonstrated excellent coverage of concepts relevant to patients’ (n=10 own treatment experiences and no new concepts were identified. Patients’ expectations of rituximab SC were conceptually consistent with items included in the RASQ-SC, suggesting that the tool is also conceptually adequate. In 1,051 patients from PrefMab and MabCute, correlations with domains such as “RASQ: Physical Impacts” and “CTSQ: Feelings About Side Effects”, “RASQ: Physical Impacts” and “CTSQ: Satisfaction With Therapy”, and “RASQ: Satisfaction” and “CTSQ: Satisfaction With Therapy”, achieved moderate-to-high correlations (>0.4 for convergent domains and <0.3 for divergent domains.Conclusion: This study supports the qualitative face and

  9. 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.

  10. Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.

    Science.gov (United States)

    Kol, Amir; Wood, Joshua A; Carrade Holt, Danielle D; Gillette, Jessica A; Bohannon-Worsley, Laurie K; Puchalski, Sarah M; Walker, Naomi J; Clark, Kaitlin C; Watson, Johanna L; Borjesson, Dori L

    2015-04-15

    Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. We injected three doses of 25 × 10(6) allogeneic MSCs from either AT or BM (a total of 75 × 10(6) MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets. Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8(+) T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls. These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8(+) T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.

  11. 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.

  12. A double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]-basimglurant and absolute bioavailability after oral administration and concomitant intravenous microdose administration of [13C6]-labeled basimglurant in humans.

    Science.gov (United States)

    Guerini, Elena; Schadt, Simone; Greig, Gerard; Haas, Ruth; Husser, Christophe; Zell, Manfred; Funk, Christoph; Hartung, Thomas; Gloge, Andreas; Mallalieu, Navita L

    2017-02-01

    1. The emerging technique of employing intravenous microdose administration of an isotope tracer concomitantly with an [ 14 C]-labeled oral dose was used to characterize the disposition and absolute bioavailability of a novel metabotropic glutamate 5 (mGlu5) receptor antagonist under clinical development for major depressive disorder (MDD). 2. Six healthy volunteers received a single 1 mg [ 12 C/ 14 C]-basimglurant (2.22 MBq) oral dose and a concomitant i.v. tracer dose of 100 μg of [ 13 C 6 ]-basimglurant. Concentrations of [ 12 C]-basimglurant and the stable isotope [ 13 C 6 ]-basimglurant were determined in plasma by a specific LC/MS-MS method. Total [ 14 C] radioactivity was determined in whole blood, plasma, urine and feces by liquid scintillation counting. Metabolic profiling was conducted in plasma, urine, blood cell pellet and feces samples. 3. The mean absolute bioavailability after oral administration (F) of basimglurant was ∼67% (range 45.7-77.7%). The major route of [ 14 C]-radioactivity excretion, primarily in form of metabolites, was in urine (mean recovery 73.4%), with the remainder excreted in feces (mean recovery 26.5%). The median t max for [ 12 C]-basimglurant after the oral administration was 0.71 h (range 0.58-1.00) and the mean terminal half-life was 77.2 ± 38.5 h. Terminal half-life for the [ 14 C]-basimglurant was 178 h indicating presence of metabolites with a longer terminal half-life. Five metabolites were identified with M1-Glucuronide as major and the others in trace amounts. There was minimal binding of drug to RBCs. IV pharmacokinetics was characterized with a mean ± SD CL of 11.8 ± 7.4 mL/h and a Vss of 677 ± 229 L. 4. The double-tracer technique used in this study allowed to simultaneously characterize the absolute bioavailability and disposition characteristics of the new oral molecular entity in a single study.

  13. A comparison in therapeutic efficacy of several time points of intravenous StemBell administration in a rat model of acute myocardial infarction

    NARCIS (Netherlands)

    Emmens, Reindert W.; Oedayrajsingh-Varma, Maikel; Woudstra, Linde; Kamp, Otto; Meinster, Elisa; van Dijk, Annemieke; Helder, Marco N.; Wouters, Diana; Zeerleder, Sacha; van Ham, S. Marieke; de Jong, Nico; Niessen, Hans W. M.; Juffermans, Lynda J. M.; Krijnen, Paul A. J.

    2017-01-01

    Adipose-derived stromal cells (ASCs) are a promising new therapeutic option for patients with acute myocardial infarction (AMI). Previously, we found that ASCs coupled to antibody-targeted microbubbles (StemBells [StBs]) improved cardiac function when administered intravenously 7 days post-AMI in

  14. Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway

    Directory of Open Access Journals (Sweden)

    Qin Y

    2016-12-01

    Full Text Available Yue Qin,1,* Suning Li,2,* Gan Zhao,2,* Xuanhao Fu,1 Xueping Xie,1 Yiyi Huang,1 Xiaojing Cheng,3 Jinbin Wei,1 Huagang Liu,1 Zefeng Lai1 1Pharmaceutical College, Guangxi Medical University, 2Department of Pharmacy, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, 3Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of “pristine” or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta and pro-fibrotic growth factors (transforming growth factor-beta 1. Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen deposition

  15. The role of qualitative and quantitative MRI assessment of multiple sclerosis lesions according to their in evaluating the efficacy of intravenous immunoglobulin G

    Energy Technology Data Exchange (ETDEWEB)

    Kocer, B. [Sedat Simavi sokak 17/32 B Blok Cankaya, Sedat Simavi sokak 17/32 B Blok Cankaya, 06550, Ankara (Turkey); Department of Neurology, Gazi University Faculty of Medicine, 06510, Ankara (Turkey); Yildirim-Guerel, S.; Tali, E.T.; Isik, S. [Department of Radiology, Gazi University Faculty of Medicine, 06510, Ankara (Turkey); Irkec, C. [Department of Neurology, Gazi University Faculty of Medicine, 06510, Ankara (Turkey)

    2004-04-01

    We evaluation of the role of determining the distribution of brain-stem, cerebellar and cerebral lesions in number and volume by MRI in determining the efficiency of treatment of multiple sclerosis (MS). We studied 24 patients diagnosed as having relapsing and remitting MS, of whom 12 received intravenous immunoglobulin G; a control group of 12 were given placebo. In a double-blind study, MRI was obtained initially and at 3, 6 and 9 months, and interpreted without knowledge of clinical findings, laboratory tests or treatment. The lesions were classified according to their distribution and evaluated qualitatively and quantitatively. Each patient was also examined clinically and scored according to the expanded disability status scale (EDSS) following every MRI examination. All patients in the treatment group showed significant improvement. The lesions decreased in both in size and number in all sites. In the control group lesions increased both in number and size in all sites, but only the increase between 3and 6 months was statistically significant. In both groups, significant apparent changes were detected in the cerebellum and brain stem. Volumetric evaluation was found to be more helpful than qualitative assessment. (orig.)

  16. The role of qualitative and quantitative MRI assessment of multiple sclerosis lesions according to their in evaluating the efficacy of intravenous immunoglobulin G

    International Nuclear Information System (INIS)

    Kocer, B.; Yildirim-Guerel, S.; Tali, E.T.; Isik, S.; Irkec, C.

    2004-01-01

    We evaluation of the role of determining the distribution of brain-stem, cerebellar and cerebral lesions in number and volume by MRI in determining the efficiency of treatment of multiple sclerosis (MS). We studied 24 patients diagnosed as having relapsing and remitting MS, of whom 12 received intravenous immunoglobulin G; a control group of 12 were given placebo. In a double-blind study, MRI was obtained initially and at 3, 6 and 9 months, and interpreted without knowledge of clinical findings, laboratory tests or treatment. The lesions were classified according to their distribution and evaluated qualitatively and quantitatively. Each patient was also examined clinically and scored according to the expanded disability status scale (EDSS) following every MRI examination. All patients in the treatment group showed significant improvement. The lesions decreased in both in size and number in all sites. In the control group lesions increased both in number and size in all sites, but only the increase between 3and 6 months was statistically significant. In both groups, significant apparent changes were detected in the cerebellum and brain stem. Volumetric evaluation was found to be more helpful than qualitative assessment. (orig.)

  17. Continuous infusion versus intermittent flushing to prevent loss of function of peripheral intravenous catheters used for drug administration in newborn infants.

    Science.gov (United States)

    Flint, A; McIntosh, D; Davies, M W

    2005-10-19

    The use of peripheral intravenous cannulae is common in newborn babies. Many of them require an intravenous line only for medications and not for fluid. Currently there is little uniformity in methods used to maintain cannula patency. The object of this review was to determine which method was better for maintaining intravenous lines used in neonates for intravenous medication only: intermittent flushing or continuous infusion We searched The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), CINAHL (from 1982 to June 2004) and MEDLINE (from 1966 to June 2004) . Randomised controlled trials comparing continuous infusion to intermittent flushing to maintain patency of intravenous cannulas. Units of randomisation might include individual catheters or individual babies. Three reviewers independently assessed trial quality and extracted data. Two studies were eligible for inclusion. In one study only one of our primary outcomes was available: the duration of cannula patency for the first cannula used per infant was slightly longer in the continuous infusion group, but not significantly so, with a mean difference of -4.3 hours (95% CI -18.2 to 9.7). In the second study, only one of our primary outcomes was available: the mean (SD) number cannulas used per infant in the first 48 hours was less in the intermittent flush group with a mean difference of -0.76 cannulas (95% CI -1.37 to -0.15). No results were available for any of our other primary outcomes: in the published report, results were reported per catheter rather than per infant, a number of infants received more than one intravenous catheter (39 infants received an unknown number of catheters). The overall duration of cannula patency was significantly longer in the intermittent flush group with a mean duration of patency in the intermittent flush group of 2.1 days (SD 1.0) compared with the continuous infusion group where the mean duration of patency was 1.0 days (SD 0

  18. Comparative chlorpyrifos pharmacokinetics via multiple routes of exposure and vehicles of administration in the adult rat

    International Nuclear Information System (INIS)

    Smith, Jordan Ned; Campbell, James A.; Busby-Hjerpe, Andrea L.; Lee, Sookwang; Poet, Torka S.; Barr, Dana B.; Timchalk, Charles

    2009-01-01

    Chlorpyrifos (CPF) is a commonly used organophosphorus pesticide. A number of toxicity and mechanistic studies have been conducted in animals, where CPF has been administered via a variety of different exposure routes and dosing vehicles. This study compared chlorpyrifos (CPF) pharmacokinetics using oral, intravenous (IV), and subcutaneous (SC) exposure routes and corn oil, saline/Tween 20, and dimethyl sulfoxide (DMSO) as dosing vehicles. Two groups of rats were co-administered target doses (5 mg/kg) of CPF and isotopically labeled CPF (L-CPF). One group was exposed by both oral (CPF) and IV (L-CPF) routes using saline/Tween 20 vehicle; whereas, the second group was exposed by the SC route using two vehicles, corn oil (CPF) and DMSO (L-CPF). A third group was only administered CPF by the oral route in corn oil. For all treatments, blood and urine time course samples were collected and analyzed for 3,5,6-trichloro-2-pyridinol (TCPy), and isotopically labeled 3,5,6-trichloro-2-pyridinol (L-TCPy). Peak TCPy/L-TCPy concentrations in blood (20.2 μmol/l), TCPy/L-TCPy blood AUC (94.9 μmol/l h), and percent of dose excreted in urine (100%) were all highest in rats dosed orally with CPF in saline/Tween 20 and second highest in rats dosed orally with CPF in corn oil. Peak TCPy concentrations in blood were more rapidly obtained after oral administration of CPF in saline/Tween 20 compared to all other dosing scenarios (>1.5 h). These results indicate that orally administered CPF is more extensively metabolized than systemic exposures of CPF (SC and IV), and vehicle of administration also has an effect on absorption rates. Thus, equivalent doses via different routes and/or vehicles of administration could potentially lead to different body burdens of CPF, different rates of bioactivation to CPF-oxon, and different toxic responses. Simulations using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF are consistent with these possibilities

  19. 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.

  20. Effects of intravenous administration of bone marrow stromal stem cells on cognitive impairment of the whole-brain irradiated rat models

    International Nuclear Information System (INIS)

    Ding Weijun; Wang Jianhua; Zhu Min; Chen Baoguo; Wang Yang

    2007-01-01

    Objective: To explore the effect of intravenous infusion of bone marrow stromal stem cells(MSCs) on cognitive function of rats after whole brain irradiation. Methods: MSCs were isolated and cultured from adult rats. After Sprague-Dawly female rats were anaesthetized with chloral hydrate, their whole cerebrum was irradiated with a single dose of 20 Gy by 6 MV X-ray. Seven days after irradiation, 4 x 106 Hoechst33342-1abelled MSCs were intravenously injected into the tail vein of these rats. Four and 8 weeks after transplantation, the learning and memorizing ability was measured with the Y maze test. Immunohistochemical method was used to identify MSCs or ceils derived from MSCs in the brain. Results: The learning and memorizing ability of irradiation groups were significantly different from that of normal control group (P < 0.01). Significant improvement of cognitive impairment was observed in rats treated with MSCs at 4 and 8 weeks after transplantation as compared with the controll groups (P<0.05). This showed that the MSCs survived and were localized to the brain tissue. The number of Hoechst33342 immunohistofluorescence positive cells and double-immunostaining cells significantly decreased in 8 weeks group as compared with the 4 weeks group. Conclusion: Marrow stromal stem cells delivered to the irradiation brain tissue through intravenous route improve the cognitive impairment after whole brain irradiation. These cells may survive and differentiate in the brain tissue of irradiated rats. (authors)

  1. Administration

    DEFF Research Database (Denmark)

    Bogen handler om den praksis, vi kalder administration. Vi er i den offentlige sektor i Danmark hos kontorfolkene med deres sagsmapper, computere, telefoner,, lovsamlinger,, retningslinier og regneark. I bogen udfoldes en mangfoldighed af konkrete historier om det administrative arbejde fra...... forskellige områder i den offentlige sektor. Hensigten er at forstå den praksis og faglighed der knytter sig til det administrative arbejde...

  2. Adverse effects of intravenous acetazolamide administration for evaluation of cerebrovascular reactivity using brain perfusion single-photon emission computed tomography in patients with major cerebral artery steno-occlusive diseases

    International Nuclear Information System (INIS)

    Saito, Hideo; Ogasawara, Kuniaki; Suzuki, Taro; Kuroda, Hiroki; Kobayashi, Masakazu; Yoshida, Kenji; Kubo, Yoshitaka; Ogawa, Akira

    2011-01-01

    Adverse effects of intravenous acetazolamide administration for evaluation of cerebrovascular reactivity using brain perfusion single-photon emission computed tomography (SPECT) were prospectively investigated in 100 patients with major cerebral artery, atherosclerotic, and steno-occlusive diseases. All patients underwent two SPECT studies (with and without acetazolamide challenge) at an interval of 2 or 3 days, received a questionnaire immediately after each SPECT study, and returned the answered questionnaire within 7 days after the study. None of the 100 patients studied experienced any symptoms during the SPECT study without acetazolamide challenge. Sixty-three patients (63%) developed symptoms during the SPECT study with acetazolamide challenge, such as headache, nausea, dizziness, tinnitus, numbness of the extremities, motor weakness of the extremities, and general malaise 1-3 hours (mean 1.6 hours) after administration of acetazolamide, and these symptoms lasted for 0.5-72 hours (mean 7.9 hours). Multivariate statistical analysis revealed that younger age (95% confidence interval [CI] 0.896-0.980, p=0.0047) and female sex (95% CI 1.178-16.129, p=0.0274) were significantly associated with development of symptoms with acetazolamide challenge. The incidences of the development of symptoms with acetazolamide challenge were 91% (21/23) and 41% (12/29) in subgroups of women <70 years and men ≥70 years, respectively. Patients should be informed of such adverse effects of intravenous acetazolamide administration prior to the acetazolamide challenge test for evaluation of cerebrovascular reactivity. (author)

  3. Adverse effects of intravenous acetazolamide administration for evaluation of cerebrovascular reactivity using brain perfusion single-photon emission computed tomography in patients with major cerebral artery steno-occlusive diseases

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Hideo; Ogasawara, Kuniaki; Suzuki, Taro; Kuroda, Hiroki; Kobayashi, Masakazu; Yoshida, Kenji; Kubo, Yoshitaka; Ogawa, Akira [Iwate Medical Univ., School of Medicine, Morioka, Iwate (Japan)

    2011-07-15

    Adverse effects of intravenous acetazolamide administration for evaluation of cerebrovascular reactivity using brain perfusion single-photon emission computed tomography (SPECT) were prospectively investigated in 100 patients with major cerebral artery, atherosclerotic, and steno-occlusive diseases. All patients underwent two SPECT studies (with and without acetazolamide challenge) at an interval of 2 or 3 days, received a questionnaire immediately after each SPECT study, and returned the answered questionnaire within 7 days after the study. None of the 100 patients studied experienced any symptoms during the SPECT study without acetazolamide challenge. Sixty-three patients (63%) developed symptoms during the SPECT study with acetazolamide challenge, such as headache, nausea, dizziness, tinnitus, numbness of the extremities, motor weakness of the extremities, and general malaise 1-3 hours (mean 1.6 hours) after administration of acetazolamide, and these symptoms lasted for 0.5-72 hours (mean 7.9 hours). Multivariate statistical analysis revealed that younger age (95% confidence interval [CI] 0.896-0.980, p=0.0047) and female sex (95% CI 1.178-16.129, p=0.0274) were significantly associated with development of symptoms with acetazolamide challenge. The incidences of the development of symptoms with acetazolamide challenge were 91% (21/23) and 41% (12/29) in subgroups of women <70 years and men {>=}70 years, respectively. Patients should be informed of such adverse effects of intravenous acetazolamide administration prior to the acetazolamide challenge test for evaluation of cerebrovascular reactivity. (author)

  4. Pharmacokinetics of guaifenesin following administration of multiple doses to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Stanley, S D; Benson, D; Arthur, R M

    2016-08-01

    Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration in order to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 2 g of guaifenesin orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum guaifenesin concentrations were determined and pharmacokinetic parameters calculated. Guaifenesin was rapidly absorbed (Tmax of 15 min) following oral administration. The Cmax was 681.3 ± 323.8 ng/mL and 1080 ± 732.8 following the first and last dose, respectively. The serum elimination half-life was 2.62 ± 1.24 h. Average serum guaifenesin concentrations remained above the LOQ of the assay (0.5 ng/mL) by 48 h postadministration of the final dose in 3 of 9 horses. © 2016 John Wiley & Sons Ltd.

  5. Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

    International Nuclear Information System (INIS)

    Waidyanatha, Suramya; Johnson, Jerry D.; Hong, S. Peter; Robinson, Veronica Godfrey; Gibbs, Seth; Graves, Steven W.; Hooth, Michelle J.; Smith, Cynthia S.

    2013-01-01

    Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C max and AUC ∞ increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC ∞ for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain:plasma ratios

  6. Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Johnson, Jerry D.; Hong, S. Peter [Battelle Memorial Institute, Columbus, OH 43201 (United States); Robinson, Veronica Godfrey [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Gibbs, Seth; Graves, Steven W. [Battelle Memorial Institute, Columbus, OH 43201 (United States); Hooth, Michelle J.; Smith, Cynthia S. [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)

    2013-09-01

    Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ∞} increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ∞} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain

  7. Tolerization of an established αb-crystallin-reactive T-cell response by intravenous antigen

    NARCIS (Netherlands)

    Verbeek, R.; Mark, K. van der; Wawrousek, E.F.; Plomp, A.C.; Noort, J.M. van

    2007-01-01

    Tolerance induction to prevent activation of a naïve T-cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an

  8. Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study.

    Science.gov (United States)

    Fleming, J O; Isaak, A; Lee, J E; Luzzio, C C; Carrithers, M D; Cook, T D; Field, A S; Boland, J; Fabry, Z

    2011-06-01

    Probiotic treatment strategy based on the hygiene hypothesis, such as administration of ova from the non-pathogenic helminth, Trichuris suis, (TSO) has proven safe and effective in autoimmune inflammatory bowel disease. To study the safety and effects of TSO in a second autoimmune disease, multiple sclerosis (MS), we conducted the phase 1 Helminth-induced Immunomodulatory Therapy (HINT 1) study. Five subjects with newly diagnosed, treatment-naive relapsing-remitting multiple sclerosis (RRMS) were given 2500 TSO orally every 2 weeks for 3 months in a baseline versus treatment control exploratory trial. The mean number of new gadolinium-enhancing magnetic resonance imaging (MRI) lesions (n-Gd+) fell from 6.6 at baseline to 2.0 at the end of TSO administration, and 2 months after TSO was discontinued, the mean number of n-Gd+ rose to 5.8. No significant adverse effects were observed. In preliminary immunological investigations, increases in the serum level of the cytokines IL-4 and IL-10 were noted in four of the five subjects. TSO was well tolerated in the first human study of this novel probiotic in RRMS, and favorable trends were observed in exploratory MRI and immunological assessments. Further investigations will be required to fully explore the safety, effects, and mechanism of action of this immunomodulatory treatment.

  9. Informed consent for the administration of an intravenous contrast agent: importance and determinants of patient refusal; Consentimiento informado para la administracion de contraste intravenoso. Importancia y factores determinantes del rechazo por los pacientes

    Energy Technology Data Exchange (ETDEWEB)

    Martel, J. [Fundacion Hospital Alcorcon. Madrid (Spain); Garcia-Diaz, J. D. [Hospital Universitario Principe de Asturias. Alcala de Henares. Madrid (Spain)

    1999-07-01

    We proposed to determine the proportion of patients who refuse to undergo intravenous contrast administration and the factors that influence their refusal. Our series consisted of 442 patients who were supposed to undergo imaging studies involving the intravenous injection of an iodine contrast. In a personal interview, the patients were issued a questionnaire specifically designed for this study. The following parameters were recorded: sex, age, inpatient or outpatient status, medical history available, person who informed them about the procedure, person signing the informed consent (patient or other) , highest academic degree, attitude toward receiving the information and degree of concern after reading and signing the consent form. In our series 8.6% of the patients (95% confidence interval: 6-11.2) refused to sign the informed consent form. In addition, there were a number of patients who delayed the procedure or hindered the daily work schedule by some other means. When the relationship between each of the variables studied and refusal to sign the consent form was assessed, significant associations were observed between the latter and the academic level of the patient, his or her degree of concern and having received the information from a trained person. There was also a nearly significant trend toward the association between refusal and the patient's background. Relatively few patients refuse to sign the informed consent to receive intravenous contrast administration but this negative decision interferes with the health care practice. It is possible to identify certain correctable factors that influence the patient in this respect. (Author) 13 refs.

  10. Evaluation of the hemodynamic effects of intravenous administration of ionic and nonionic contrast materials: implications for deriving physiologic measurements from computed tomography and digital cardiovascular imaging

    International Nuclear Information System (INIS)

    Higgins, C.B.; Berber, K.H.; Mattrey, R.F.; Slutsky, R.A.

    1982-01-01

    The effects of intravenous injection of an ionic contrast material (Renografin-76 [meglumine sodium diatrizoate]) on left ventricular pressure, internal diameter, and wall thickness, and on coronary and femoral hemodynamics were compared with those of a hydrolytically stable nonionic contrast material (iohexol). Renografin-76 caused drastic biphasic changes in left ventricular pressure and dp/dt (rate of change of left ventricular pressure), and moderate changes in end systolic dimension. Iohexol caused little or no change in left ventricular pressure and dimensions. In addition, Renografin-76 caused marked arterial hypotension and large increases in coronary and femoral blood lows, while iohexol caused no significant change in arterial pressure and coronary blood flow, and a mild increase in femoral blood flow. Based on these findings, it is concluded that iohexol is preferable to standard ionic contrast material for deriving basal physiologic information from computed tomographic and digital vascular studies

  11. How cannabis causes paranoia: using the intravenous administration of ∆9-tetrahydrocannabinol (THC) to identify key cognitive mechanisms leading to paranoia.

    Science.gov (United States)

    Freeman, Daniel; Dunn, Graham; Murray, Robin M; Evans, Nicole; Lister, Rachel; Antley, Angus; Slater, Mel; Godlewska, Beata; Cornish, Robert; Williams, Jonathan; Di Simplicio, Martina; Igoumenou, Artemis; Brenneisen, Rudolf; Tunbridge, Elizabeth M; Harrison, Paul J; Harmer, Catherine J; Cowen, Philip; Morrison, Paul D

    2015-03-01

    Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis-∆(9)-tetrahydrocannabinol (THC)-causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  12. Intravenous Glutamine Administration Modulates TNF-α/IL-10 Ratio and Attenuates NFkB Phosphorylation in a Protein Malnutrition Model.

    Science.gov (United States)

    Santos, Andressa Cristina Antunes; Correia, Carolina Argondizo; de Oliveira, Dalila Cunha; Nogueira-Pedro, Amanda; Borelli, Primavera; Fock, Ricardo Ambrosio

    2016-12-01

    Protein malnutrition (PM) is a major public health problem in developing countries, affecting the inflammatory response and increasing susceptibility to opportunistic infections. For this reason, an adequate nutritional intervention can improve the quality of life of patients. Glutamine (GLN) is a nonessential amino acid, but can be considered "conditionally essential" for macrophage function in stress situations, in which it plays a role in the improvement of the inflammatory response. Concerning this issue, in the current study, it was of interest to evaluate some biological aspects of peritoneal cells from a protein malnutrition (PM) mouse model challenged with lipopolysaccharide (LPS) and treated intravenously with GLN. Two-month-old male Balb/c mice were subjected to a low-protein diet (2 % protein) and stimulated intravenously with LPS 1 h prior to the injection of 0.75 mg/kg GLN. Malnourished animals showed a reduced number of total peritoneal cells. Malnourished animals stimulated with LPS or LPS plus GLN did not show differences in peritoneal cell counts; however, the control group showed increased cellularity after LPS stimulus, which was reversed after GLN injection. Further, in the animals from both groups stimulated with LPS, GLN decreased the circulating levels of TNF-α and the levels of TNF-α produced by peritoneal cells; additionally, GLN decreased the IL-10 circulating levels in the malnourished animals stimulated with LPS. In addition, peritoneal cells of the control and malnourished groups stimulated with LPS showed a negative modulation of the NFkB signaling pathway after GLN injection. In conclusion, this study shows that GLN has the capacity to reduce TNF-α synthesis as well as to act as a negative regulator of NFkB phosphorylation, leading to a positive outcome in the control of TNF-α production.

  13. 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.

  14. The repopulation of lymph nodes of dogs after 1200 R whole-body x-irradiation and intravenous administration of mononuclear blood leukocytes.

    Science.gov (United States)

    Nelson, B; Calvo, W; Fliedner, T M; Herbst, E; Bruch, C; Schnappauf, H P; Flad, H D

    1976-08-01

    Fresh and cryopreserved autologous or allogeneic mononuclear blood cells (MBCs) intravenously injected in 1200 R total-body x-irradiated dogs repopulated lymph nodes within 10 days after tranfusion. Several parameters of the lymphopoietic regeneration were correlated with the number of cells transfused and with the number of colony-forming units contained in the cell suspension when they were cultured in agar (CFUc). Values within the normal or close to normal range were reached in the mesenteric nodes of most of the animals transfused with 10 X 10(9) MBC or more. These values were obtained when 5 X 10(5) CFUc or more were transfused. Axillary nodes showed lower values than mesenteric nodes. They were mostly under the normal range but well over those of the irradiated controls. Frozen and thawed MBCs seem to be as effective as fresh cells for lymphopoietic restoration. The mesenteric nodes of dogs transfused with allogeneic MBCs showed higher cellularity and larger cortical-paracortical areas than those of dogs tranfused with approximately the same number of autologous cells. The repopulation of lymph nodes parallels that of the marrow.

  15. Effect of intravenous administration of d-lysergic acid diethylamide on subsequent protein synthesis in a cell-free system derived from brain.

    Science.gov (United States)

    Cosgrove, J W; Clark, B D; Brown, I R

    1981-03-01

    An initiating cell-free protein synthesis system derived from brain was utilized to demonstrate that the intravenous injection of d-lysergic acid diethylamide (LSD) to rabbits induced a transient inhibition of translation following a brief stimulatory period. Subfractionation of the brain cell-free system into postribosomal supernatant (PRS) and microsome fractions demonstrated that LSD in vivo induced alterations in both of these fractions. In addition to the overall inhibition of translation in the cell-free system, differential effects were noted, i.e., greater than average relative decreases in in vitro labeling of certain brain proteins and relative increases in others. The brain proteins of molecular weights 75K and 95K, which were increased in relative labeling under conditions of LSD-induced hyperthermia, are similar in molecular weight to two of the major "heat shock" proteins reported in tissue culture systems. Injection of LSD to rabbits at 4 degrees C prevented LSD-induced hyperthermia but behavioral effects of the drug were still apparent. The overall decrease in cell-free translation was still observed but the differential labeling effects were not. LSD appeared to influence cell-free translation in the brain at two dissociable levels: (a) an overall decrease in translation that was observed even in the absence of LSD-induced hyperthermia and (b) differential labeling effects on particular proteins that were dependent on LSD-induced hyperthermia.

  16. Repopulation of lymph nodes of dogs after 1200 R whole-body x-irradiation and intravenous administration of mononuclear blood leukocytes

    International Nuclear Information System (INIS)

    Nelson, B.; Calvo, W.; Fliedner, T.M.; Herbst, E.; Bruch, C.; Schnappauf, H.P.; Flad, H.D.

    1976-01-01

    Fresh and cryopreserved autologous or allogeneic mononuclear blood cells (MBCs) intravenously injected in 1200 R total-body x-irradiated dogs repopulated lymph nodes within 10 days after transfusion. Several parameters of the lymphopoietic regeneration were correlated with the number of cells transfused and with the number of colony-forming units contained in the cell suspension when they were cultured in agar (CFU/sub c/). Values within the normal or close to normal range were reached in the mesenteric nodes of most of the animals transfused with 10 x 10 9 MBC or more. These values were obtained when 5 x 10 5 CFU/sub c/ or more were transfused. Axillary nodes showed lower values than mesenteric nodes. They were mostly under the normal range but well over those of the irradiated controls. Frozen and thawed MBCs seem to be as effective as fresh cells for lymphopoietic restoration. The mesenteric nodes of dogs transfused with allogeneic MBCs showed higher cellularity and larger cortical-paracortical areas than those of dogs transfused with approximately the same number of autologous cells. The repopulation of lymph nodes parallels that of the marrow

  17. The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates.

    Science.gov (United States)

    Meany, Holly J; Fox, Elizabeth; McCully, Cynthia; Tucker, Chris; Balis, Frank M

    2008-08-01

    Erlotinib hydrochloride is a small molecule inhibitor of epidermal growth factor receptor (EGFR). EGFR is over-expressed in primary brain tumors and solid tumors that metastasize to the central nervous system. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics of erlotinib and its active metabolite OSI-420 after an intravenous (IV) dose in a non-human primate model. Erlotinib was administered as a 1 h IV infusion to four adult rhesus monkeys. Serial blood and CSF samples were drawn over 48 h and erlotinib and OSI-420 were quantified with an HPLC/tandem mass spectroscopic assay. Pharmacokinetic parameters were estimated using non-compartmental and compartmental methods. CSF penetration was calculated from the AUC(CSF):AUC(plasma). Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma was 30% (range 12-59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUC(CSF):AUC(plasma)) of erlotinib and OSI-420 was OSI-420 are measurable in CSF after an IV dose. The drug exposure (AUC) in the CSF is limited relative to total plasma concentrations but is substantial relative the free drug exposure in plasma.

  18. Effects of intravenous administration of two volumes of calcium solution on plasma ionized calcium concentration and recovery from naturally occurring hypocalcemia in lactating dairy cows.

    NARCIS (Netherlands)

    Doze, J.G.; Donders, R.; Kolk, J.H. van der

    2008-01-01

    OBJECTIVE: To compare the effects of administration of 2 volumes of a calcium solution (calcium oxide and calcium gluconate) on plasma ionized calcium concentration (PICaC) and clinical recovery from naturally occurring hypocalcemia (NOHC; milk fever) in lactating dairy cows. ANIMALS: 123 cows with

  19. Targeted Intra-arterial Transplantation of Stem Cells to the Injured CNS is More Effective than Intravenous Administration - Engraftment is Dependent on Cell Type and Adhesion Molecule Expression

    DEFF Research Database (Denmark)

    Lundberg, Johan; Södersten, Erik; Sundström, Erik

    2011-01-01

    with inflammation, such as traumatic brain injury, there is a transient up-regulation of ICAM-1 and VCAM-1 which might provide enviromental cues for migration of stem cells from blood to parenchyma. The aim of this study was to i) analyze the effect of intra-arterial administration on cellular engraftment, ii...

  20. [Observing the density increase curve after intravenous contrast medium administration using a bolus triggering system: a method for detection cardiovascular disorders?].

    Science.gov (United States)

    Stückle, C A; Kickuth, R; Kirchner, E M; Liermann, D; Kirchner, J

    2002-06-01

    Recently bolus tracking systems were developed to improve the timing of intravenous contrast media application in helical computed tomography. We investigated the benefit of this new method as a parameter of the cardiac function. Retrospective analysis of 64 patients which incidentally underwent bolus triggered contrast enhanced helical CT and invasive investigation of the heart within one week. All examinations were performed on the CT scanner Somatom Plus 4 Volume Zoom (Siemens Corp., Forchheim, Germany) using the C.A.R.E. Bolus software. This performs repetitive low-dose test scans (e.g. for the abdomen: 140 kV, 20 mA, Tl 0.5 s) and measures the Hounsfield attenuation (increase over the baseline) in a preselected region of interest. The displayed increase of vascular density over the time after peripheral contrast media injection (75 ml lopromid (300 mg/ml), 2 ml/s) was categorised to three types: (a) rapid increase, (b) deceleration before a 100 HE threshold was reached and (c) one or more peaks. The findings of the invasive investigation of the heart were correlated to the findings of the bolus-tracking measurements. The examinations were categorized as follows: 19 type A, 34 type B, 11 type C. We found a high significant correlation between the type of the Hounsfield attenuation and systolic pressure in the left ventricle. There was no correlation between the type of the Hounsfield attenuation and the diastolic pressure in the left ventricle, the pressures related to the right ventricle or the ejection fraction. The bolus-tacking system showed a sensitivity of 53, a specificity of 82, an accuracy of 70%, a positive predictive value of 70% and a negative predictive value of 70% in detection of left heart failure. The bolus tracking system C.A.R.E.-bolus often shows atypical Hounsfield attenuation in cases of cardiac failure but is not suitable as a screening method of the cardiopulmonary function.

  1. 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.

  2. Systemic administration of mesenchymal stem cells combined with parathyroid hormone therapy synergistically regenerates multiple rib fractures.

    Science.gov (United States)

    Cohn Yakubovich, Doron; Sheyn, Dmitriy; Bez, Maxim; Schary, Yeshai; Yalon, Eran; Sirhan, Afeef; Amira, May; Yaya, Alin; De Mel, Sandra; Da, Xiaoyu; Ben-David, Shiran; Tawackoli, Wafa; Ley, Eric J; Gazit, Dan; Gazit, Zulma; Pelled, Gadi

    2017-03-09

    A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures. The combination of human MSCs (hMSCs) and a clinically relevant PTH dose was studied using immunosuppressed rats. Segmental defects were created in animals' fifth and sixth ribs. The rats were divided into four groups: a negative control group, in which animals received vehicle alone; the PTH-only group, in which animals received daily subcutaneous injections of 4 μg/kg teriparatide, a pharmaceutical derivative of PTH; the hMSC-only group, in which each animal received five injections of 2 × 10 6 hMSCs; and the hMSC + PTH group, in which animals received both treatments. Longitudinal in vivo monitoring of bone formation was performed biweekly using micro-computed tomography (μCT), followed by histological analysis. Fluorescently-dyed hMSCs were counted using confocal microscopy imaging of histological samples harvested 8 weeks after surgery. PTH significantly augmented the number of hMSCs that homed to the fracture site. Immunofluorescence of osteogenic markers, osteocalcin and bone sialoprotein, showed that PTH induced cell differentiation in both exogenously administered cells and resident cells. μCT scans revealed a significant increase in bone volume only in the hMSC + PTH group, beginning by the 4 th week after surgery. Eight weeks after surgery, 35% of ribs in the hMSC + PTH group had complete bone bridging, whereas there was complete bridging in only 6.25% of ribs (one rib) in the PTH-only group and in none of the ribs in the other groups. Based on the μCT scans, biomechanical analysis using the micro-finite element method demonstrated that

  3. Multiple model predictive control for optimal drug administration of mixed immunotherapy and chemotherapy of tumours.

    Science.gov (United States)

    Sharifi, N; Ozgoli, S; Ramezani, A

    2017-06-01

    Mixed immunotherapy and chemotherapy of tumours is one of the most efficient ways to improve cancer treatment strategies. However, it is important to 'design' an effective treatment programme which can optimize the ways of combining immunotherapy and chemotherapy to diminish their imminent side effects. Control engineering techniques could be used for this. The method of multiple model predictive controller (MMPC) is applied to the modified Stepanova model to induce the best combination of drugs scheduling under a better health criteria profile. The proposed MMPC is a feedback scheme that can perform global optimization for both tumour volume and immune competent cell density by performing multiple constraints. Although current studies usually assume that immunotherapy has no side effect, this paper presents a new method of mixed drug administration by employing MMPC, which implements several constraints for chemotherapy and immunotherapy by considering both drug toxicity and autoimmune. With designed controller we need maximum 57% and 28% of full dosage of drugs for chemotherapy and immunotherapy in some instances, respectively. Therefore, through the proposed controller less dosage of drugs are needed, which contribute to suitable results with a perceptible reduction in medicine side effects. It is observed that in the presence of MMPC, the amount of required drugs is minimized, while the tumour volume is reduced. The efficiency of the presented method has been illustrated through simulations, as the system from an initial condition in the malignant region of the state space (macroscopic tumour volume) transfers into the benign region (microscopic tumour volume) in which the immune system can control tumour growth. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Pharmacokinetics of detomidine following intravenous or oral-transmucosal administration and sedative effects of the oral-transmucosal treatment in dogs.

    Science.gov (United States)

    Messenger, Kristen M; Hopfensperger, Marie; Knych, Heather K; Papich, Mark G

    2016-04-01

    To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. 12 healthy adult dogs. In phase 1, detomidine was administered by IV (0.5 mg/m(2)) or OTM (1 mg/m(2)) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m(2)) or detomidine gel by OTM administration (0.5 mg/m(2)), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.

  5. Detection of endotoxins in radiopharmaceutical preparations--I. Comparison of rabbit hyperthermia after intravenous or intrathecal administration of reference endotoxin preparations

    Energy Technology Data Exchange (ETDEWEB)

    Merlin, L; Bruneau, J; Cohen, Y; Michaud, T

    1986-01-01

    The rise of the rabbit internal temperature after endotoxin injection is related to the route of administration. A rise of 1.71 +/- 0.411/sup 0/C is obtained after i.v. injection of 1 ng/kg Escherichia coli 0111.B.4 endotoxin. An increase of 1.93 +/- 0.236/sup 0/C is obtained after suboccipital intrathecal injection of 0.1 ng/kg of the same endotoxin; with the intrathecal route, the hyperthermia is induced by E. coli endotoxin after a dose ten times lower than with i.v. injection as shown by statistical analysis.

  6. A Comparison of the Pharmacokinetics and Pulmonary Lymphatic Exposure of a Generation 4 PEGylated Dendrimer Following Intravenous and Aerosol Administration to Rats and Sheep.

    Science.gov (United States)

    Ryan, Gemma M; Bischof, Robert J; Enkhbaatar, Perenlei; McLeod, Victoria M; Chan, Linda J; Jones, Seth A; Owen, David J; Porter, Christopher J H; Kaminskas, Lisa M

    2016-02-01

    Cancer metastasis to pulmonary lymph nodes dictates the need to deliver chemotherapeutic and diagnostic agents to the lung and associated lymph nodes. Drug conjugation to dendrimer-based delivery systems has the potential to reduce toxicity, enhance lung retention and promote lymphatic distribution in rats. The current study therefore evaluated the pharmacokinetics and lung lymphatic exposure of a PEGylated dendrimer following inhaled administration. Plasma pharmacokinetics and disposition of a 22 kDa PEGylated dendrimer were compared after aerosol administration to rats and sheep. Lung-derived lymph could not be sampled in rats and so lymphatic transport of the dendrimer from the lung was assessed in sheep. Higher plasma concentrations were achieved when dendrimer was administered to the lungs of rats as a liquid instillation when compared to an aerosol. Plasma pharmacokinetics were similar between sheep and rats, although some differences in disposition patterns were evident. Unexpectedly, less than 0.5% of the aerosol dose was recovered in pulmonary lymph. The data suggest that rats provide a relevant model for assessing the pharmacokinetics of inhaled macromolecules prior to evaluation in larger animals, but that the pulmonary lymphatics are unlikely to play a major role in the absorption of nanocarriers from the lungs.

  7. Optimization of health-care organization and perceived improvement of patient comfort by switching from intra-venous BU four-times-daily infusions to a once-daily administration scheme in adult hematopoietic stem cell recipients.

    Science.gov (United States)

    Xhaard, A; Rzepecki, P; Valcarcel, D; Santarone, S; Fürst, S; Serrano, D; De Angelis, G; Krüger, W; Scheid, C

    2014-04-01

    Previous studies have shown an equivalent pharmacokinetic profile between four-times-daily (4QD) and once-daily (QD) administration of intra-venous (IV) BU, without increased toxicity. We assess the impact of a switch in IV BU from a 4QD to a QD schedule, in terms of health-care organization, staff working conditions, quality of care dispensed and perceived patient comfort. Clinicians, nurses and pharmacists from nine allogeneic transplantation units in five European countries were interviewed face to face. Overall perception of QD versus 4QD BU was very positive. Both administration schemes were evaluated to be equally efficaciousZ. QD BU was perceived to be safer and more convenient. Clinicians and nurses perceived that patient comfort was improved, due to fewer complications associated with repeated infusions, and avoiding night infusions associated with stress, anxiety and decreased quality of sleep. Switching from 4QD to QD BU had a significant impact on health-care organization, with a better integration in the overall management and usual timelines in the pharmacies and transplantation units. Time spent to prepare and administer BU was significantly reduced, leading to potential financial savings that merit further assessment and would be of particular interest in the current economic climate.

  8. 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.

  9. The Development of Multiple Intelligence Capabilities for Early Childhood Development Center, Local Administration Organization in Chaiyaphum Province

    Science.gov (United States)

    Siphai, Sunan; Supandee, Terdsak; Raksapuk, Chunpit; Poopayang, Piangkhae; Kratoorerk, Sangsan

    2017-01-01

    The aim of this research is to promote multiple intelligence capabilities for Early Childhood Care Center of a Sub-district Administration Organization in Chaiyaphum Province. The sample applied were 61 children aging between 3 and 5 years old at Child Development Center, Tambon Ban Kok, Amphoe Chaturus, Chaiyaphum Province, who were selected…

  10. A fast-track anaemia clinic in the Emergency Department: cost-analysis of intravenous iron administration for treating iron-deficiency anaemia.

    Science.gov (United States)

    Quintana-Díaz, Manuel; Muñoz-Romo, Raúl; Gómez-Ramírez, Susana; Pavía, José; Borobia, Alberto M; García-Erce, José A; Muñoz, Manuel

    2017-09-01

    A fast-track anaemia clinic (FTAC) for the management of moderate-to-severe iron-deficiency anaemia (IDA) was established in our Emergency Department in 2010. In this FTAC, the replacement of packed red cell transfusion by ferric carboxymaltose administration was proven to be safe and effective. The aim of this study was a cost-analysis of IDA management in the FTAC, comparing this management with the previous standard care pathway consisting of packed red cell transfusion, if needed, and referral to outpatient specialised care. A cost study was performed for patients with IDA who were at risk of requiring transfusion (haemoglobin costs in the FTAC were compared to those theoretically incurred if these patients had been managed using the standard care pathway. In addition, a sensitivity analysis considering variations of up to ±30% in ferric carboxymaltose and packed red cell acquisition costs was performed (49 possible scenarios). Between 2012 and 2015, 238 IDA patients were treated in the FTAC. The average treatment cost was € 594±337/patient in the FTAC group and € 672±301/patient in the standard care pathway group, with a saving of € 78±28/patient (95% CI, 22-133; pcosts in the FTAC (€ 480-722/patient), compared with those of the standard care pathway (€ 550-794/patient), resulted in significant cost-savings for all studied scenarios (€ 51-104/patient; pcost-saving compared with the standard care pathway.

  11. Administración oral de preparado parenteral de vitamina K en anticoagulación excesiva por warfarina Oral administration of intravenous preparation of Vitamin K for excessive anticoagulation due to warfarin

    Directory of Open Access Journals (Sweden)

    Yoleima Lozada

    2012-04-01

    Full Text Available La warfarina es frecuentemente usada en la terapia anticoagulante actual, su acción debe ser monitorizada usando el tiempo de protrombina expresado como International Normalized Ratio (INR; cuando se excede el rango de seguridad se puede administrar vitamina K (Vit-K, preferentemente por vía oral. Dicha presentación no está disponible en Venezuela. Se realizó un ensayo clínico, doble ciego, donde a 20 pacientes, edad 18-60 años, sin sangrado e INR inicial de 6 a 10 inclusive; les fue suspendida la warfarina e inmediatamente agrupados al azar a recibir dosis única de Vit-K (oral 1.25mg de Vit-K fraccionada de una presentación parenteral o placebo. El punto final primario, INR Anticoagulation therapy with warfarin, a common clinical practice, needs to be monitored using protombine time expressed as the International Normalized Ratio (INR; when safety range is exceeded, Vitamin K (Vit-K could be administered with preference orally. In Venezuela the specific oral preparation for Vit-K is not available. This is a double blinded, randomized, placebo controlled, clinical trial; 20 patients, age 18-60 year with initial INR ≥ 6, ≤10, were randomized to oral Vit-K 1.25mg (prepared from intravenous presentation or placebo plus withholding warfarin. INR < 3.5 at 24 hours of treatment (the primary end point was achieved by 70% among Vit-K, and 20% among placebo patients; given an absolute risk reduction (ARR, of 50% (CI95%: 14.4-85.6 ρ = 0.028, NNT 2 (CI95%: 1.3 - 6.9. No adverse events were recorded including INR < 2 at 24 hours of treatment administration. Our results are consistent with studies where specific oral presentation of Vit-K was used. The results indicate that oral administration of Vit-K, prepared from an intravenous Vit-K preparation, is safe and more effective to revert excessive anticoagulation than simply withholding warfarin, in places where specific preparation of oral Vit-K is not available or too expensive.

  12. Pharmacokinetics of Second-Line Antituberculosis Drugs after Multiple Administrations in Healthy Volunteers.

    Science.gov (United States)

    Park, Sang-In; Oh, Jaeseong; Jang, Kyungho; Yoon, Jangsoo; Moon, Seol Ju; Park, Jong Sun; Lee, Jae Ho; Song, Junghan; Jang, In-Jin; Yu, Kyung-Sang; Chung, Jae-Yong

    2015-08-01

    Therapeutic drug monitoring (TDM) of second-line antituberculosis drugs would allow for optimal individualized dosage adjustments and improve drug safety and therapeutic outcomes. To evaluate the pharmacokinetic (PK) characteristics of clinically relevant, multidrug treatment regimens and to improve the feasibility of TDM, we conducted an open-label, multiple-dosing study with 16 healthy subjects who were divided into two groups. Cycloserine (250 mg), p-aminosalicylic acid (PAS) (5.28 g), and prothionamide (250 mg) twice daily and pyrazinamide (1,500 mg) once daily were administered to both groups. Additionally, levofloxacin (750 mg) and streptomycin (1 g) once daily were administered to group 1 and moxifloxacin (400 mg) and kanamycin (1 g) once daily were administered to group 2. Blood samples for PK analysis were collected up to 24 h following the 5 days of drug administration. The PK parameters, including the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve during a dosing interval at steady state (AUCτ), were evaluated. The correlations between the PK parameters and the concentrations at each time point were analyzed. The mean Cmax and AUCτ, respectively, for each drug were as follows: cycloserine, 24.9 mg/liter and 242.3 mg · h/liter; PAS, 65.9 mg/liter and 326.5 mg · h/liter; prothionamide, 5.3 mg/liter and 22.1 mg · h/liter; levofloxacin, 6.6 mg/liter and 64.4 mg · h/liter; moxifloxacin, 4.7 mg/liter and 54.2 mg · h/liter; streptomycin, 42.0 mg/liter and 196.7 mg · h/liter; kanamycin, 34.5 mg/liter and 153.5 mg · h/liter. The results indicated that sampling at 1, 2.5, and 6 h postdosing is needed for TDM when all seven drugs are administered concomitantly. This study indicates that PK characteristics must be considered when prescribing optimal treatments for patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02128308.). Copyright © 2015, American Society for

  13. Vascular air embolism after contrast administration on 64 row multiple detector computed tomography: A prospective analysis

    Directory of Open Access Journals (Sweden)

    Kushaljit S Sodhi

    2015-01-01

    Full Text Available Background: Vascular air embolism is being progressively reported as a nonfatal event with increase in use of computed tomography (CT as a diagnostic modality. This study was undertaken to study the frequency and site of vascular air embolism in patients undergoing contrast-enhanced CT (CECT and analyze CT parameters that influence its prevalence and final outcome. Materials and Methods: This was a prospective study approved by departmental ethics committee. Presence and location of air emboli in 200 patients who underwent CT scan of chest on a 64 detector scanner was recorded. We analyzed the role of various factors that could influence the prevalence of air embolism after injection of contrast in CECT scans. These factors included the amount of contrast injected, rate of flow of injection of contrast, site of injection of contrast, and size of intravenous access line. Results: Iatrogenic vascular air emboli were seen in 14 patients (7% of total. The locations of air emboli were main pulmonary artery in 12 (6% of total, left brachiocephalic vein in 3 (1.5% of total, right atrial appendage in 4 (2% of total, and superior vena cava (SVC in 1 (0.5% patient. There was no association between volume of contrast, flow rate, site and size of intravenous access, and presence of air emboli. Conclusion: Radiologists as well as referring physicians should be aware of vascular air embolism, which can occur after contrast injection in patients undergoing CT scan. Age, volume of contrast, flow rate of pressure injector, and site and size of venous cannula do not influence the likelihood or incidence of detection of venous air emboli on CT scans.

  14. Pre-emptive administration of intravenous acetaminophen with transversus abdominis plane block (tap-blocke in the prevention of fentanil-induced hyperalgesia in pediatric oncological patient undergoing abdominal surgery

    Directory of Open Access Journals (Sweden)

    Dmytro Dmytriiev

    2015-10-01

      Abstract Background: Acetaminophen is a selective COX-2 agonist that has been shown to decrease the intensity of opioid-induced hyperalgesia (OIH in children. We aimed to investigate the effects of preemptive administration of intravenous acitomenofen  in the prevention of high-dose fentanil-induced hyperalgesia in pediatric patients. Methods: 45 patients of  American Society of Anesthesiologists physical status 1-3 undergoing abdominal surgery were randomly assigned to one of the following three groups. each of which received either IV acetaminophen  (an initial dose of 1.5 ml/kg for 40 min before before the induction of anesthesia or placebo saline 40 min before the induction of anesthesia and intraoperative fentanil infusion: group LFH received a placebo and 0.05 μg/kg/min fentanil; group FH received a placebo and 0.3 μg/kg/min fentanil; and group AFH received IV preemptive administration acetaminophen  and TAP-blocke bupivacaine 0,3 mg/kg.             Results: The mechanical hyperalgesia threshold 12 hr after surgery was significantly lower in group FH than in the other two groups. Postoperative pain intensity using visual analog scale (VAS and cumulative volume of a patient controlled analgesia (PCA containing morphine over 12 hr were significantly greater in group FH than in group AFH. The time to the first postoperative analgesic requirement was significantly shorter in group RH than in the other two groups. The sevoflurane requirement was significantly greater in group LFH than in the other groups. The frequency of hypotension and bradycardia was significantly higher, but shivering and postoperative nausea and vomiting were significantly lower in group AFH than in the other two groups. Conclusions: High-doses of fentanil induced hyperalgesia, which presented a decreased mechanical hyperalgesia threshold, enhanced pain intensity, a shorter time to first postoperative analgesic requirement, and greater morphine consumption, but IV

  15. Portable Intravenous Fluid Production Device for Ground Use

    Data.gov (United States)

    National Aeronautics and Space Administration — There are several medical conditions require the administration of intravenous (IV) fluids, but limitations of mass, volume, shelf-life, transportation, and local...

  16. Histology of peri-implant bone in a failed implant retrieved from an area of osteonecrosis of the jaw in a patient suffering from multiple myeloma and treated with intravenous bisphosphonates

    Directory of Open Access Journals (Sweden)

    Marco Degidi

    2012-03-01

    Full Text Available Background: Osteonecrosis of the jaw (ONJ has been reported in the past few years in patients undergoing treatment with bisphosphonates (BP. Few published histological studies of ONJ can be found in the literature and no study has been reported on the peri-implant bone around a dental implant retrieved from an area of ONJ. The aim of the present case was to report the histology of the peri-implant bone around an implant retrieved from an area of ONJ. Materials and methods: Multiple myeloma was diagnosed to a 72-year-old male. The patient underwent treatment with intravenous pamidronate for 2 years and with intravenous zoledronate for additional 3 years. Five years after the diagnosis, 7 immediately loaded dental implants were inserted in the mandible. A preoperative panoramic radiography did show no pre-existing bone lesions. No healing of the post-extraction sockets of the right third molar and of the left second molar was observed. Three years after the implant insertion a breakdown of the oral mucosa covering the implants was observed. The most distal implant was retrieved with a trephine bur, due to mobility. Discussion: The histological findings showed some areas with osseointegration in patients undergoing BP treatment for malignant disease. Conclusion: There is certainly a temporal association between BP use and development of ONJ, but a correlation does not necessarily mean causation. Moreover, generalisations about this complex relationship cannot be made on the basis of a single case report. In patients undergoing intravenous treatment, clinicians must be aware of the increased risk of implant failure and, probably, implant insertion should be avoided at all, until more conclusive data are available.

  17. Identifying a size-specific hazard of silica nanoparticles after intravenous administration and its relationship to the other hazards that have negative correlations with the particle size in mice

    Science.gov (United States)

    Handa, Takayuki; Hirai, Toshiro; Izumi, Natsumi; Eto, Shun-ichi; Tsunoda, Shin-ichi; Nagano, Kazuya; Higashisaka, Kazuma; Yoshioka, Yasuo; Tsutsumi, Yasuo

    2017-03-01

    Many of the beneficial and toxic biological effects of nanoparticles have been shown to have a negative correlation with particle size. However, few studies have demonstrated biological effects that only occur at specific nanoparticle sizes. Further elucidation of the size-specific biological effects of nanoparticles may reveal not only unknown toxicities, but also novel benefits of nanoparticles. We used surface-unmodified silica particles with a wide range of diameters and narrow size intervals between the diameters (10, 30, 50, 70, 100, 300, and 1000 nm) to investigate the relationship between particle size and acute toxicity after intravenous administration in mice. Negative correlations between particle size and thrombocytopenia, liver damage, and lethal toxicity were observed. However, a specific size-effect was observed for the severity of hypothermia, where silica nanoparticles with a diameter of 50 nm induced the most severe hypothermia. Further investigation revealed that this hypothermia was mediated not by histamine, but by platelet-activating factor, and it was independent of the thrombocytopenia and the liver damage. In addition, macrophages/Kupffer cells and platelets, but not neutrophils, play a critical role in the hypothermia. The present results reveal that silica nanoparticles have particle size-specific toxicity in mice, suggesting that other types of nanoparticles may also have biological effects that only manifest at specific particle sizes. Further study of the size-specific effects of nanoparticles is essential for safer and more effective nanomedicines.

  18. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

    2010-04-01

    To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

  19. Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol

    International Nuclear Information System (INIS)

    Geletneky, Karsten; Hajda, Jacek; Huesing, Johannes; Rommelaere, Jean; Schlehofer, Joerg R; Leuchs, Barbara; Dahm, Michael; Krebs, Ottheinz; Knebel Doeberitz, Magnus von; Huber, Bernard

    2012-01-01

    The treatment of patients with malignant brain tumors remains a major oncological problem. The median survival of patients with glioblastoma multiforme (GBM), the most malignant type, is only 15 months after initial diagnosis and even less after tumor recurrence. Improvements of standard treatment including surgery and radio-chemotherapy have not lead to major improvements. Therefore, alternative therapeutics such as oncolytic viruses that specifically target and destroy cancer cells are under investigation. Preclinical data of oncolytic parvovirus H-1 (H-1PV) infection of glioma cells demonstrated strong cytotoxic and oncosuppressing effects, leading to a phase I/IIa trial of H-1PV in patients with recurrent GBM (ParvOryx01). ParvOryx01 is the first trial with a replication competent oncolytic virus in Germany. ParvOryx01 is an open, non-controlled, two groups, intra-group dose escalation, single center, phase I/IIa trial. 18 patients with recurrent GBM will be treated in 2 groups of 9 patients each. Treatment group 1 will first receive H-1PV by intratumoral injection and second by administration into the walls of the tumor cavity during tumor resection. In treatment group 2 the virus will initially be injected intravenously and afterwards, identical to group 1, into the surrounding brain tissue during tumor removal. Main eligibility criteria are: age of 18 years, unifocal recurrent GBM, amenable to complete or subtotal resection. Dose escalation will be based on the Continual Reassessment Method. The primary objective of the trial is local and systemic safety and tolerability and to determine the maximum tolerated dose (MTD). Secondary objectives are proof of concept (PoC) and Progression-free Survival (PFS) up to 6 months. This is the first trial with H-1PV in patients with recurrent GBM. The risks for the participants appear well predictable and justified. Furthermore, ParvOryx01 will be the first assessment of combined intratumoral and intravenous application

  20. Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

    Science.gov (United States)

    Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

    2015-06-01

    Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

  1. 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 ...

  2. Multiple sclerosis in Germany: data analysis of administrative prevalence and healthcare delivery in the statutory health system.

    Science.gov (United States)

    Höer, Ariane; Schiffhorst, Guido; Zimmermann, Anne; Fischaleck, Johann; Gehrmann, Luise; Ahrens, Henrik; Carl, Gunther; Sigel, Karl-Otto; Osowski, Ulrike; Klein, Maria; Bleß, Hans-Holger

    2014-09-10

    Healthcare-utilization data for multiple sclerosis (MS) are scarce in Germany. The Purpose of the study was to analyse administrative prevalence of MS, medication use and type of specialists involved in MS treatment in the outpatient setting in Bavaria. Pseudonymized claims data from Bavarian Statutory Health Insurance (SHI)-accredited physicians were used. Administrative prevalence of MS was defined as having ≥1 MS diagnosis (International Classification of Diseases, 10th edition, code G35) documented by a neurologist or psychiatrist, or ≥1 prescription for disease-modifying drugs (DMDs)). The administrative prevalence calculated for Bavaria was projected to Germany. DMD prescription and involvement of different specialities in health care service for MS patients was analysed. Administrative prevalence of MS in Bavaria increased from 0.123% to 0.175% of insured persons between 2005 and 2009; when projected, this yielded ~102,000-143,000 patients with MS in the German population. The percentage of patients receiving ≥1 DMD prescription increased from 45.5% to 50.5%. Patients with MS were mainly treated by neurologists in the ambulatory care setting. These results provide important information on the administrative prevalence of MS in Bavaria and on healthcare provision for patients, which is relevant for resource planning in the healthcare sector.

  3. Multiple Introduction and Naturally Occuring Drug Resistance of HCV among HIV-Infected Intravenous Drug Users in Yunnan: An Origin of China's HIV/HCV Epidemics.

    Directory of Open Access Journals (Sweden)

    Min Chen

    Full Text Available The human immunodeficiency virus 1 (HIV-1 epidemic in China historically stemmed from intravenous drug users (IDUs in Yunnan. Due to a shared transmission route, hepatitis C virus (HCV/HIV-1 co-infection is common. Here, we investigated HCV genetic characteristics and baseline drug resistance among HIV-infected IDUs in Yunnan.Blood samples of 432 HIV-1/HCV co-infected IDUs were collected from January to June 2014 in six prefectures of Yunnan Province. Partial E1E2 and NS5B genes were sequenced. Phylogenetic, evolutionary and genotypic drug resistance analyses were performed.Among the 293 specimens successfully genotyped, seven subtypes were identified, including subtypes 3b (37.9%, 111/293, 3a (21.8%, 64/293, 6n (14.0%, 41/293, 1b (10.6%, 31/293, 1a (8.2%, 24/293, 6a (5.1%, 15/293 and 6u (2.4%, 7/293. The distribution of HCV subtypes was mostly related to geographic location. Subtypes 3b, 3a, and 6n were detected in all six prefectures, however, the other four subtypes were detected only in parts of the six prefectures. Phylogeographic analyses indicated that 6n, 1a and 6u originated in the western prefecture (Dehong and spread eastward and showed genetic relatedness with those detected in Burmese. However, 6a originated in the southeast prefectures (Honghe and Wenshan bordering Vietnam and was transmitted westward. These subtypes exhibited different evolutionary rates (between 4.35×10-4 and 2.38×10-3 substitutions site-1 year-1 and times of most recent common ancestor (tMRCA, between 1790.3 and 1994.6, suggesting that HCV was multiply introduced into Yunnan. Naturally occurring resistance-associated mutations (C316N, A421V, C445F, I482L, V494A, and V499A to NS5B polymerase inhibitors were detected in direct-acting antivirals (DAAs-naïve IDUs.This work reveals the temporal-spatial distribution of HCV subtypes and baseline HCV drug resistance among HIV-infected IDUs in Yunnan. The findings enhance our understanding of the characteristics and

  4. Intravenous maternal -arginine administration to twin-bearing ewes, during late pregnancy, is associated with increased fetal muscle mTOR abundance and postnatal growth in twin female lambs.

    Science.gov (United States)

    Sales, F; Sciascia, Q; van der Linden, D S; Wards, N J; Oliver, M H; McCoard, S A

    2016-06-01

    The aims of this study were to determine whether parenteral Arg administered to well-fed twin-bearing ewes from 100 to 140 d of pregnancy influences fetal skeletal muscle growth, the abundance and activation of mechanistic target of rapamycin (mTOR) protein, and postnatal muscle growth of the offspring. Ewes fed 100% of NRC-recommended nutrient requirements for twin-bearing ewes were administered an intravenous bolus of either 345 μmol Arg HCl/kg BW or saline solution (Control) 3 times per day. At 140 d of pregnancy (P140), a group of 11 Control and 9 Arg-treated ewes were euthanized and hind leg muscles and longissimus dorsi (LD) were excised and weighed. A sample of LD was snap frozen in liquid nitrogen for later analysis of free AA (FAA) concentration, mTOR abundance and phosphorylation, and biochemical indices (DNA, RNA, and protein content). For the remaining 25 ewes (Arg, = 13, and Control, = 12), Arg administration was continued until the initiation of parturition and ewes were allowed to lamb. Lambs were weaned at postnatal Day 82 and grazed on pasture until postnatal day 153 (PN153), when a subset of 20 lambs ( = 10 per group) was euthanized. At P140, only the psoas major was heavier in the Arg-administered group compared with the Control group. Female lambs from ewes supplemented with Arg (Arg-F) had increased abundance of total mTOR, RNA concentration, and RNA:DNA ratio in LD compared with female lambs from Control ewes (Con-F), whereas males did not differ. At PN153, Arg-F were heavier than Con-F and had heavier LD and plantaris and a trend for heavier psoas major muscles compared with Con-F. In contrast, BW and individual muscle weights did not differ in male lambs. Lambs from Arg-treated ewes had heavier semimembranosus and tended to have heavier biceps femoris compared with Control lambs. The RNA concentration in LD was greater in Arg-F compared with Con-F, and DNA concentration was greater in the Arg group compared with the Control group. In

  5. T1 Shortening in the Globus Pallidus after Multiple Administrations of Gadobutrol: Assessment with a Multidynamic Multiecho Sequence.

    Science.gov (United States)

    Kang, Koung Mi; Choi, Seung Hong; Hwang, Moonjung; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho

    2018-04-01

    Purpose To determine the association between the administration of the macrocyclic contrast medium gadobutrol and T1 relaxation time in the brains of patients with normal renal function by using multidynamic multiecho (MDME) magnetic resonance (MR) imaging sequences. Materials and Methods The institutional review board approved this retrospective study, and the need to obtain written informed consent was waived. This study included 46 patients (revealed by an electronic medical record search) who had received one or more gadobutrol injections and a maximum of one MR imaging contrast medium injection other than gadobutrol before MDME sequence acquisition. One radiologist performed quantitative analyses of regions of interest on quantitative T1 maps twice to cover the normal-appearing globus pallidus (GP), frontal white matter, frontal cortex, and thalamus. The number of administrations and the cumulative dose of gadobutrol, age, intervals between administrations, sex, and treatment were investigated. Univariable and multivariable linear regression analyses of the T1 values in four brain regions and the GP-to-thalamus signal intensity (SI) ratio were performed. P values of less than the Bonferroni-corrected value of .01 were considered to indicate significant differences. Results Intraobserver reproducibility was good to excellent (intraclass correlation coefficients, 0.62-0.81). Because of high multicollinearity between the number of gadobutrol administrations and accumulated dose (r = 0.96, P .01). Conclusion Multiple exposures to gadobutrol are associated with T1 shortening in the GP. © RSNA, 2017 Online supplemental material is available for this article.

  6. Elimination of cetirizine following administration of multiple doses to exercised thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

    2016-10-01

    Cetirizine is an antihistamine used in performance horses for the treatment of hypersensitivity reactions and as such a withdrawal time is necessary prior to competition. The objective of the current study was to describe the disposition and elimination of cetirizine following oral administration in order to provide additional serum concentration data upon which appropriate regulatory recommendations can be established. Nine exercised thoroughbred horses were administered 0.4 mg/kg of cetirizine orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum cetirizine concentrations were determined and selected pharmacokinetic parameters determined. The serum elimination half-life was 5.83 ± 0.841 h. Average serum cetirizine concentrations were still above the LOQ of the assay (0.05 ng/mL) at 48 h (final sample collected) postadministration of the final dose. © 2016 John Wiley & Sons Ltd.

  7. Bayesian models and meta analysis for multiple tissue gene expression data following corticosteroid administration

    Directory of Open Access Journals (Sweden)

    Kelemen Arpad

    2008-08-01

    Full Text Available Abstract Background This paper addresses key biological problems and statistical issues in the analysis of large gene expression data sets that describe systemic temporal response cascades to therapeutic doses in multiple tissues such as liver, skeletal muscle, and kidney from the same animals. Affymetrix time course gene expression data U34A are obtained from three different tissues including kidney, liver and muscle. Our goal is not only to find the concordance of gene in different tissues, identify the common differentially expressed genes over time and also examine the reproducibility of the findings by integrating the results through meta analysis from multiple tissues in order to gain a significant increase in the power of detecting differentially expressed genes over time and to find the differential differences of three tissues responding to the drug. Results and conclusion Bayesian categorical model for estimating the proportion of the 'call' are used for pre-screening genes. Hierarchical Bayesian Mixture Model is further developed for the identifications of differentially expressed genes across time and dynamic clusters. Deviance information criterion is applied to determine the number of components for model comparisons and selections. Bayesian mixture model produces the gene-specific posterior probability of differential/non-differential expression and the 95% credible interval, which is the basis for our further Bayesian meta-inference. Meta-analysis is performed in order to identify commonly expressed genes from multiple tissues that may serve as ideal targets for novel treatment strategies and to integrate the results across separate studies. We have found the common expressed genes in the three tissues. However, the up/down/no regulations of these common genes are different at different time points. Moreover, the most differentially expressed genes were found in the liver, then in kidney, and then in muscle.

  8. 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 ...

  9. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

    Science.gov (United States)

    Flammer, Keven; Nettifee Osborne, Julie A; Webb, Donna J; Foster, Laura E; Dillard, Stacy L; Davis, Jennifer L

    2008-01-01

    To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

  10. A retrospective study of epidural and intravenous steroids after percutaneous endoscopic lumbar discectomy for large lumbar disc herniation

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2017-02-01

    Conclusion: Patients who underwent PELD with epidural steroid administration for large lumbar disc herniation showed favorable curative effect compared with those who underwent PELD with intravenous steroid administration.

  11. Microbiological quality of some brands of intravenous fluids ...

    African Journals Online (AJOL)

    SERVER

    2007-10-04

    Oct 4, 2007 ... Food, Drug Administration and Control (NAFDAC), have on many occasions ... products from 8 manufacturers were tested for their ... Table 1. Microbial contamination level of brand of intravenous fluids produced by some.

  12. 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)

  13. [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.

  14. Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects.

    Science.gov (United States)

    Suriyo, Tawit; Pholphana, Nanthanit; Ungtrakul, Teerapat; Rangkadilok, Nuchanart; Panomvana, Duangchit; Thiantanawat, Apinya; Pongpun, Wanwisa; Satayavivad, Jutamaad

    2017-06-01

    Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata , 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person. Georg Thieme Verlag KG Stuttgart · New York.

  15. Intravenous polyclonal human immunoglobulins in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Per Soelberg

    2008-01-01

    to methylprednisolone does not make remission of symptoms faster or more complete. IVIG does not seem to be of any benefit to chronic visual or motor symptoms in MS. In secondary progressive MS, IVIG has not shown any effect on disease progression, relapses or new magnetic resonance imaging lesions. Experimental...... studies in the MS model experimental autoimmune encephalomyelitis in rats demonstrate that IVIG has to be administered at the time of induction of a relapse in order to be effective. In conclusion, IVIG can be considered as a second-line treatment to approved therapies for relapsing-remitting MS...... and magnetic resonance imaging outcome measures Udgivelsesdato: 2008...

  16. Optimizing the use of intravenous therapy in internal medicine.

    Science.gov (United States)

    Champion, Karine; Mouly, Stéphane; Lloret-Linares, Celia; Lopes, Amanda; Vicaut, Eric; Bergmann, Jean-François

    2013-10-01

    We aimed to evaluate the impact of physicians' educational programs in the reduction of inappropriate intravenous lines in internal medicine. Fifty-six French internal medicine units were enrolled in a nationwide, prospective, blinded, randomized controlled trial. Forms describing the patients with an intravenous line and internal medicine department characteristics were filled out on 2 separate days in January and April 2007. Following the first visit, all units were randomly assigned to either a specific education program on the appropriate indications of an intravenous line, during February and March 2007, or no training (control group). The Investigators' Committee then blindly evaluated the clinical relevance of the intravenous line according to pre-established criteria. The primary outcome was the percentage of inappropriate intravenous lines. During January 2007, intravenous lines were used in 475 (24.9%) of the 1910 hospitalized patients. Of these, 80 (16.8%) were considered inappropriate. In April 2007, 416 (22.8%) of the 1823 hospitalized patients received an intravenous line, which was considered in 10.2% (21/205) of patients managed by trained physicians, versus 16.6% (35/211) of patients in the control group (relative difference 39%; 95% confidence interval, -0.6-13.3; P = .05). Reduced intravenous administration of fluids, antibiotics, and analgesics accounted for the observed decrease. The use of a simple education program reduced the rate of inappropriate intravenous lines by almost 40% in an internal medicine setting (NCT01633307). Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

    Science.gov (United States)

    Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

    2017-06-01

    The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The Various Forms of Insulin Secretion Response to the Intravenous and Oral Administration of Glucose in Non-Insulin-Dependent Diabetes Mellitus; Les Differentes Modalites de Reponse Insulino-Secretrice Lors de Charges Veineuse et Orale en Glucose dans le Diabete Sucre Non Insulino-Dependant

    Energy Technology Data Exchange (ETDEWEB)

    Mirouze, J.; Orsetti, A.; Lapinski, H. [Clinique des Maladies Metaboliques et Endocriniennes, Hopital St-Eloi, Montpellier (France)

    1970-02-15

    On the basis of 68 observations on advanced diabetes mellitus (20 cases), latent diabetes with obesity (12 cases), chemical diabetes with subjective symptoms (26 cases) and 10 observations of obesity without diabetes, the authors have analysed the various forms of insulin secretion response to the intravenous and oral administration of glucose. The response appeared to be totally withdrawn in advanced diabetes mellitus although the patients were still capable of responding to stimulation with glucagon. In the two other forms of diabetes described, the response to stimulation by intravenous administration was less marked than in normal subjects. With oral administration, on the other hand, the response was greater, although the insulin secreted in this case appeared ineffective in cases of obesity but effective in conditions without obesity due to the hypoglycaemic effect. (author) [French] A l'aide de 68 observations de diabete sucre evolue (20 cas), latent avec obesite (12 cas), chimique avec malaises (26 cas) et de 10 observations d'obesite sans diabete, les auteurs analysent les differentes modalites de riposte insulino- secretrice lors des charges en glucose, veineuse et orale. La riposte s'avere totalement effondree dans le diabete evolue, mais susceptible de repondre encore a la stimulation par le glucagon. Dans les deux autres formes de diabete decrites, la stimulation par charge veineuse est reduite par rapport au sujet normal alors qu'elle est majoree apres charge orale mais l'insuline ainsi secretee parait inefficace dans l'obesite et efficace puisque hypoglycemiante lors de malaises sans obesite. (author)

  19. 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.

  20. 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)

  1. 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)

  2. 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

  3. Population pharmacokinetics of buprenorphine following a two-stage intravenous infusion in healthy volunteers

    DEFF Research Database (Denmark)

    Jensen, Mette Lykke; Foster, David J.R.; Upton, Richard N.

    2007-01-01

    The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only.......The aim of this investigation was to characterize the pharmacokinetics of buprenorphine following administration of an intravenous (i.v.) infusion. To date, the population kinetics of buprenorphine has been described for bolus administration only....

  4. 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...

  5. Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Conte, Giorgio; Minotti, Marta; De Piano, Francesca [Universita degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan (Italy); Preda, Lorenzo [Universita degli Studi di Pavia, Department of Clinical-Surgical Diagnostic and Pediatric Sciences, Pavia (Italy); National Center of Oncological Hadrontherapy (CNAO Foundation), Division of Radiology, Pavia (Italy); Cocorocchio, Emilia; Ferrucci, Pier Francesco [European Institute of Oncology, Melanoma and Sarcoma Medical Oncology Division, Milan (Italy); Raimondi, Sara [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Giannitto, Caterina; Petralia, Giuseppe [European Institute of Oncology, Division of Radiology, Milan (Italy); Bellomi, Massimo [European Institute of Oncology, Division of Radiology, Milan (Italy); Universita degli Studi di Milano, Oncology and Haematology/Oncology Department, Milan (Italy)

    2017-10-15

    To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. We retrospectively included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. (orig.)

  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. Administrative Data Repository (ADR)

    Data.gov (United States)

    Department of Veterans Affairs — The Administrative Data Repository (ADR) was established to provide support for the administrative data elements relative to multiple categories of a person entity...

  8. The human experience with intravenous levodopa

    Directory of Open Access Journals (Sweden)

    Shan H Siddiqi

    2016-01-01

    Full Text Available Objective: To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies.Background: While safe intravenous (IV use of levodopa has been documented for over 50 years, regulatory supervision for pharmaceuticals given by a route other than that approved by the U.S. Food and Drug Administration (FDA has become increasingly cautious. If delivering a drug by an alternate route raises the risk of adverse events, an investigational new drug (IND application is required, including a comprehensive review of toxicity data.Methods: Over 200 articles referring to IV levodopa were examined for details of administration, pharmacokinetics, benefit and side effects.Results: We identified 142 original reports describing IVLD use in humans, beginning with psychiatric research in 1959-1960 before the development of peripheral decarboxylase inhibitors. Over 2750 subjects have received IV levodopa, and reported outcomes include parkinsonian signs, sleep variables, hormone levels, hemodynamics, CSF amino acid composition, regional cerebral blood flow, cognition, perception and complex behavior. Mean pharmacokinetic variables were summarized for 49 healthy subjects and 190 with Parkinson’s disease. Side effects were those expected from clinical experience with oral levodopa and dopamine agonists. No articles reported deaths or induction of psychosis.Conclusion: Over 2750 patients have received IV levodopa with a safety profile comparable to that seen with oral administration.

  9. 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.

  10. 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

  11. [Intravenous ethyl alcohol in metabolic resuscitation].

    Science.gov (United States)

    Agolini, G; Lipartiti, T; Zaffiri, O; Musso, L; Belloni, G P

    1980-11-01

    Intravenously administered ethyl alcohol may be effective as analgesic and hypotensive peripheric vasoactive drug. In the Intensive Care Departments parenteral ethanol administration is infrequent because no "sure dosage" can be suggested in adults and children. Liver, kidney and C.N.S. diseases can worsen; foetopathy can follow. Drug-ethanol interaction may be particularly important for some patients admitted in Intensive Care Departments. Often the potential caloric support cannot be fully utilized ("empty" calories) and seldom hyperventilation, hyperlactacidemia and impaired protein synthesis can follow.

  12. 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

  13. Enhancing the Predictive Potential of Personality: Isolating Multiple Components of Trait Expression via a Single Administration Design

    Science.gov (United States)

    2015-03-01

    109 8.0 Arts, Design, Entertainment, Media, Sports , and Recreation 100 7.4 Information Technology 86 6.3 Office and Administrative Support 74 5.5...55 4.1 Government and Public Administration 35 2.6 Community and Social Service 29 2.1 Manufacturing 29 2.1 Hospitality and Tourism 25 1.8...playing a sport ; exercising; or doing yard work or housework. % Not descriptive of me % Somewhat descriptive of me % Very descriptive of me N/A

  14. Intraosseous Urography Compared with Intravenous Urography: An Experimental Study in the Rabbit Model

    OpenAIRE

    SAĞLAM, Mutlu; UĞUREL, Şahin

    2014-01-01

    This study was performed to evaluate the feasibility of bone injection gun assisted intraosseous administration of contrast media as an alternative to the intravenous route for urography. Intravenous urographies were obtained in 6 rabbits. Urographic examinations by the intraosseous route were performed in the same animals 48 h later. After adequate anesthesia, the retroauricular vein was punctured for intravenous injection and a bone injection gun was used for intraosseous injections to the ...

  15. Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease

    DEFF Research Database (Denmark)

    Bonde, J; Svendsen, T L; Lyngborg, K

    1987-01-01

    administration of four sequential doses (0.5, 0.5, 1.0 and 2.0 mg) of ICI 141,292 was examined. HR decreased 7% (P less than 0.05) following ICI 141,292 1 mg with no further decrease following the succeeding doses. Cardiac output decreased 5.2% (P less than 0.05) following a cumulative dose of 4 mg...... as atenolol) beta 1-adrenoceptor blocking agent possessing moderate intrinsic sympathomimetic activity....

  16. Time to treatment with intravenous alteplase and outcome in stroke

    DEFF Research Database (Denmark)

    Lees, Kennedy R; Bluhmki, Erich; von Kummer, Rüdiger

    2010-01-01

    BACKGROUND: Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to trea...

  17. 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...

  18. Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

    2017-01-01

    The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection. © 2016 John Wiley & Sons Ltd.

  19. Mortality and comorbidities in patients with multiple sclerosis compared with a population without multiple sclerosis: An observational study using the US Department of Defense administrative claims database.

    Science.gov (United States)

    Capkun, Gorana; Dahlke, Frank; Lahoz, Raquel; Nordstrom, Beth; Tilson, Hugh H; Cutter, Gary; Bischof, Dorina; Moore, Alan; Simeone, Jason; Fraeman, Kathy; Bancken, Fabrice; Geissbühler, Yvonne; Wagner, Michael; Cohan, Stanley

    2015-11-01

    Data are limited for mortality and comorbidities in patients with multiple sclerosis (MS). Compare mortality rates and event rates for comorbidities in MS (n=15,684) and non-MS (n=78,420) cohorts from the US Department of Defense (DoD) database. Comorbidities and all-cause mortality were assessed using the database. Causes of death (CoDs) were assessed through linkage with the National Death Index. Cohorts were compared using mortality (MRR) and event (ERR) rate ratios. All-cause mortality was 2.9-fold higher in the MS versus non-MS cohort (MRR, 95% confidence interval [CI]: 2.9, 2.7-3.2). Frequent CoDs in the MS versus non-MS cohort were infectious diseases (6.2, 4.2-9.4), diseases of the nervous (5.8, 3.7-9.0), respiratory (5.0, 3.9-6.4) and circulatory (2.1, 1.7-2.7) systems and suicide (2.6, 1.3-5.2). Comorbidities including sepsis (ERR, 95% CI: 5.7, 5.1-6.3), ischemic stroke (3.8, 3.5-4.2), attempted suicide (2.4, 1.3-4.5) and ulcerative colitis (2.0, 1.7-2.3), were higher in the MS versus non-MS cohort. The rate of cancers was also higher in the MS versus the non-MS cohort, including lymphoproliferative disorders (2.2, 1.9-2.6) and melanoma (1.7, 1.4-2.0). Rates of mortality and several comorbidities are higher in the MS versus non-MS cohort. Early recognition and management of comorbidities may reduce premature mortality and improve quality of life in patients with MS. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Pharmacokinetics of opicapone, a third-generation COMT inhibitor, after single and multiple oral administration: A comparative study in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Gonçalves, Daniela [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Alves, Gilberto, E-mail: gilberto@fcsaude.ubi.pt [CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã (Portugal); Fortuna, Ana [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal); Soares-da-Silva, Patrício [Department of Research and Development, BIAL – Portela & Ca S.A., Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado (Portugal); MedInUP – Center for Drug Discovery and Innovative Medicines, University Porto, Porto (Portugal); Falcão, Amílcar [Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra (Portugal); CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra (Portugal)

    2017-05-15

    Opicapone is a novel potent, reversible and purely peripheral catechol-O-methyltransferase inhibitor that has been developed to be used as an adjunct to levodopa/aromatic L-amino acid decarboxylase inhibitor therapy for Parkinson's disease. Thus, this study aimed to compare the plasma pharmacokinetics of opicapone and its active metabolite (BIA 9-1079) after the administration of single and multiple oral doses to rats. Wistar rats (n = 8 per group) were orally treated with single (30, 60 or 90 mg/kg) or multiple (30 mg/kg once-daily for seven consecutive days) oral doses of opicapone. Blood samples were collected up to 24 h post-dosing through a cannula introduced in the tail vein of rats. After quantifying opicapone and BIA 9-1079 in plasma, a non-compartmental pharmacokinetic analysis was performed. Opicapone was quickly absorbed (time to reach the maximum plasma concentration ≤ 2 h) in both dosage regimens and the extent of systemic exposure to opicapone increased approximately in a dose-proportional manner after single-dosing within the studied dose range (30–90 mg/kg). Opicapone and BIA 9-1079 showed a relatively short plasma elimination half-life (1.58–4.50 h) and a small systemic accumulation after multiple-dosing. Hence, no pharmacokinetic concerns are expected when opicapone is administered with a once-daily dosing regimen. - Highlights: • Opicapone is relatively rapid absorbed after oral administration to rats. • Systemic exposure to opicapone increases approximately in a dose-proportional manner. • Opicapone and BIA 9-1079 show a small systemic accumulation after multiple-dosing.

  1. 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 ...

  2. Haematological indices in Trypanosoma brucei brucei (Federe isolate infected Nigerian donkeys (Equus asinus treated with homidium and isometamidium chloride of ciprofloxacin in broiler chickens after single intravenous and intraingluvial administration

    Directory of Open Access Journals (Sweden)

    Queen Nneka Oparah

    2017-03-01

    Full Text Available The efficacy of intramuscular administration of Homidium chloride (Novidium® and Isometamidium chloride (Sécuridium® in Nigerian donkeys (Equus asinus experimentally infected with T. b. brucei (Federe isolate was investigated. Changes in haematological and serum biochemical indices were evaluated using clinical haematology and biochemistry methods. Red blood cell (RBC count for the negative control group was significantly higher than for the positive control, Novidium® and Sécuridium®-treatment groups. Haemoglobin (Hb concentration significantly reduced in the infected untreated group compared with other groups. Packed cell volume (PCV was significantly different between negative and positive controls, and also between the infected untreated and treatment groups. There was significant reduction in platelet counts post-infection and post-treatment. Mean corpuscular volume (MCV increased significantly in the treatment groups while mean corpuscular haemoglobin concentration (MCHC significantly reduced only in the Sécuridium®-treatment group. Lymphocyte count for infected untreated was non-significantly higher than for the uninfected controls, but treatment with both trypanocides recorded further increases, which were higher compared with that of the uninfected group. Post infection and treatment, aspartate aminotransferase (AST levels increased significantly. There were non-significant differences in electrolyte ion concentrations across the groups except for chloride ion which recorded a significant reduction in the Novidium®-treatment group. This experiment revealed that Nigerian donkeys infected with T. brucei brucei (Federe isolate developed symptoms of trypanosomosis; anaemia, lymphocytosis and thrombocytopenia. Treatment with the trypanocides ameliorated effects of the infection, and results suggest that immunosuppression may not be a substantial clinical manifestation of T. brucei brucei (Federe isolate trypanosomosis in Nigerian

  3. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b{sup +} myeloid cells to the lungs and facilitates B16-F10 melanoma colonization

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Lucas E.B., E-mail: lucasebsouza@usp.br [Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Almeida, Danilo C., E-mail: gudaalmeida@gmail.com [Department of Medicine – Nephrology, Laboratory of Clinical and Experimental Immunology, Federal University of São Paulo, São Paulo, SP (Brazil); Yaochite, Juliana N.U., E-mail: ueda.juliana@gmail.com [Department of Biochemistry and Immunology, Basic and Applied Immunology Program, School of Medicine of Ribeirão Preto, University of São Paulo (Brazil); Covas, Dimas T., E-mail: dimas@fmrp.usp.br [Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Fontes, Aparecida M., E-mail: aparecidamfontes@usp.br [Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2016-07-15

    The discovery that the regenerative properties of bone marrow multipotent mesenchymal stromal cells (BM-MSCs) could collaterally favor neoplastic progression has led to a great interest in the function of these cells in tumors. However, the effect of BM-MSCs on colonization, a rate-limiting step of the metastatic cascade, is unknown. In this study, we investigated the effect of BM-MSCs on metastatic outgrowth of B16-F10 melanoma cells. In in vitro experiments, direct co-culture assays demonstrated that BM-MSCs stimulated the proliferation of B16-F10 cells in a dose-dependent manner. For in vivo experiments, luciferase-expressing B16-F10 cells were injected through tail vein and mice were subsequently treated with four systemic injections of BM-MSCs. In vivo bioluminescent imaging during 16 days demonstrated that BM-MSCs enhanced the colonization of lungs by B16-F10 cells, which correlated with a 2-fold increase in the number of metastatic foci. Flow cytometry analysis of lungs demonstrated that although mice harboring B16-F10 metastases displayed more endothelial cells, CD4 T and CD8 T lymphocytes in the lungs in comparison to metastases-free mice, BM-MSCs did not alter the number of these cells. Interestingly, BM-MSCs inoculation resulted in a 2-fold increase in the number of CD11b{sup +} myeloid cells in the lungs of melanoma-bearing animals, a cell population previously described to organize “premetastatic niches” in experimental models. These findings indicate that BM-MSCs provide support to B16-F10 cells to overcome the constraints that limit metastatic outgrowth and that these effects might involve the interplay between BM-MSCs, CD11b{sup +} myeloid cells and tumor cells. - Highlights: • BM-MSCs enhanced B16-F10 proliferation in a dose-dependent manner in vitro. • BM-MSCs facilitated lung colonization by B16-F10 melanoma cells. • BM-MSCs administration did not alter the number of endothelial cells and T lymphocytes in the lungs. • BM-MSCs enhanced

  4. 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.

  5. Signal intensity change on unenhanced T1-weighted images in dentate nucleus following gadobenate dimeglumine in patients with and without previous multiple administrations of gadodiamide

    Energy Technology Data Exchange (ETDEWEB)

    Ramalho, Joana [University of North Carolina Hospital, Chapel Hill, NC (United States); Centro Hospitalar de Lisboa Central, Lisbon (Portugal); Semelka, Richard C.; Castillo, Mauricio [University of North Carolina Hospital, Chapel Hill, NC (United States); AlObaidy, Mamdoh [University of North Carolina Hospital, Chapel Hill, NC (United States); King Faisal Specialist Hospital and Research Center, Riyadh (Saudi Arabia); Ramalho, Miguel [University of North Carolina Hospital, Chapel Hill, NC (United States); Hospital Garcia de Orta, Almada (Portugal); Nunes, Renato H. [University of North Carolina Hospital, Chapel Hill, NC (United States); Santa Casa de Misericordia de Sao Paulo, Sao Paulo (Brazil)

    2016-11-15

    To evaluate the impact of previous administration of gadodiamide and neural tissue gadolinium deposition in patients who received gadobenate dimeglumine. Our population included 62 patients who underwent at least three administrations of gadobenate dimeglumine, plus an additional contrast-enhanced last MRI for reference, divided into two groups: group 1, patients who in addition to gadobenate dimeglumine administrations had prior exposure to multiple doses of gadodiamide; group 2, patients without previous exposure to other gadolinium-based contrast agent (GBCAs). Quantitative analysis was performed on the first and last gadobenate dimeglumine MRIs in both groups. Dentate nucleus-to-middle cerebellar peduncle signal intensity ratios (DN/MCP) and relative change (RC) in signal over time were calculated and compared between groups using generalized additive model. Group 1 showed significant increase in baseline and follow-up DN/MCP compared to group 2 (p < 0.0001). The RC DN/MCP showed a non-statistically significant trend towards an increase in patients who underwent previous gadodiamide (p = 0.0735). There is increased T1 signal change over time in patients who underwent gadobenate dimeglumine and had received prior gadodiamide compared to those without known exposure to previous gadodiamide. A potentiating effect from prior gadodiamide on subsequent administered gadobenate dimeglumine may occur. (orig.)

  6. [Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study].

    Science.gov (United States)

    Zhang, Xi-ping; Zhang, Xiang; Yang, Hong-jian; Zou, De-hong; He, Xiang-ming; Yu, Xing-fei; Li, Yong-feng

    2015-07-01

    To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice. Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated. There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P drug B and L (P chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.

  7. 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.

  8. Simultaneous quantification of multiple components in rat plasma by UPLC-MS/MS and pharmacokinetic study after oral administration of Huangqi decoction.

    Science.gov (United States)

    Zeng, Jia-Kai; Li, Yuan-Yuan; Wang, Tian-Ming; Zhong, Jie; Wu, Jia-Sheng; Liu, Ping; Zhang, Hua; Ma, Yue-Ming

    2018-05-01

    A rapid, sensitive and accurate UPLC-MS/MS method was developed for the simultaneous quantification of components of Huangqi decoction (HQD), such as calycosin-7-O-β-d-glucoside, calycosin-glucuronide, liquiritin, formononetin-glucuronide, isoliquiritin, liquiritigenin, ononin, calycosin, isoliquiritigenin, formononetin, glycyrrhizic acid, astragaloside IV, cycloastragenol, and glycyrrhetinic acid, in rat plasma. After plasma samples were extracted by protein precipitation, chromatographic separation was performed with a C 18 column, using a gradient of methanol and 0.05% acetic acid containing 4mm ammonium acetate as the mobile phase. Multiple reaction monitoring scanning was performed to quantify the analytes, and the electrospray ion source polarity was switched between positive and negative modes in a single run of 10 min. Method validation showed that specificity, linearity, accuracy, precision, extraction recovery, matrix effect and stability for 14 components met the requirements for their quantitation in biological samples. The established method was successfully applied to the pharmacokinetic study of multiple components in rats after intragastric administration of HQD. The results clarified the pharmacokinetic characteristics of multiple components found in HQD. This research provides useful information for understanding the relation between the chemical components of HQD and their therapeutic effects. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Imaging of chest disease due to intravenous heroin abuse

    International Nuclear Information System (INIS)

    Lian Xuhui; Chen Zhong; Ye Wenqin

    2002-01-01

    Objective: To study the imaging findings of the chest disease due to intravenous heroin abuse. Methods: Twenty-five cases of clinically confirmed chest disease due to intravenous heroin abuse were retrospectively analyzed. 25 cases had conventional X-ray film, 6 cases had CT scanning, and 6 cases had echocardiography scanning. Results: On X-ray and CT, the following signs were found: lung making manifold (n = 5), small patchy shadow (n = 15), pneumatocele (n = 16), small cavity (n = 16), small node (n = 7), pleural effusion (n = 8 ), pneumothorax (n = 2), hydropneumothorax (n = 6), pulmonary edema (n = 2), megacardia (n = 11), multiple-shaped lesion (n = 20). On echocardiography, tricuspid vegetation (n = 4) and tricuspid insufficiency (n = 4) were found. Conclusion: The X-ray and CT manifestations of chest inflammation due to intravenous heroin abuse are multiple. The multiple small cavities and pneumatoceles sign are of some value in the diagnosis of lung inflammation due to intravenous heroin abuse among young patients

  10. 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.

  11. 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.

  12. [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.

  13. Increases in Intravenous Magnesium Use among Hospitalized Patients: An Institution Cross-Sectional Experience

    Directory of Open Access Journals (Sweden)

    Bryce A. Kiberd

    2015-06-01

    Full Text Available Background: Among hospitalized patients, indications for the measurement of magnesium levels and treatment of hypomagnesemia with intravenous magnesium are not well defined. Recently, there have been reports of worldwide shortages of intravenous magnesium sulphate. Objective: To examine secular trends in the administration of intravenous magnesium on hospital wards at a tertiary care institution. The secondary objective is to identify factors associated with magnesium use among admitted patients. Methods: Retrospective cross-section review of hospitalized patients at a single Canadian tertiary care center. Utilization of non-parental nutrition intravenous magnesium from 2003 to 2013 stratified by hospital ward was examined. In addition, patient level data from select wards (including medical and surgical services was examined at early and more recent time period (4/2006 versus 4/2013. Results: Among the 248,329 hospitalized patients, intravenous magnesium use increased by 2.86 fold from 2003 to 2013. Not all wards had an increase whereas some had nearly a 10 fold increase in use. In the sample ( n = 769, (adjusting for admission magnesium level, presence of an indication for intravenous magnesium, ward location, comorbidity and demographics intravenous magnesium administration was higher (25.8 % versus 5.5 % in 2013 versus 2006 (OR 13.91 (95 % CI, 6.21–31.17, p < 0.001. Despite this increase in intravenous magnesium administration, <3 % of patients were admitted on oral magnesium in 2006 and 2013. For patients receiving intravenous magnesium only a minority were discharged on oral therapy despite low levels. Conclusions: This center has witnessed a considerable increase in the use of in-hospital intravenous magnesium over the last 6 years that cannot be explained for by medical indications. The risks and benefits of this therapy deserve further study. If this change in practice is representative of other North American hospitals, it may be

  14. Administration of Home Intravenous Chemotherapy to Children by their Parents.

    Science.gov (United States)

    McCall, Claire; Mannion, Michelle; Hilliard, Carol; Lannon, Pamela; McKenna, Fiona; O'Marcaigh, Aengus; Slevin, Teresa; Smith, Owen; Storey, Lorna

    Caring for a child with cancer can disrupt family life and financial stability, in addition to affecting the child's social, emotional, and educational development. Health care providers must consider ways to minimize the negative impact of illness and hospitalization on the child and family. This study evaluates a nationwide initiative to educate and support parents to administer chemotherapy to their child in their home. A questionnaire was circulated to parents participating in a home chemotherapy program from 2009 to 2014 (n = 140), seeking their perspective on the education program, and the benefits and concerns associated with administering home chemotherapy. Data analysis was conducted using a combination of descriptive statistics and content analysis. Questionnaires were received from 108 parents (response rate = 77%). Overall, the program was positively evaluated with 100% of parents (n = 108) reporting that the training met their needs. More than one-third of parents (41%, n = 44) initially felt nervous about home chemotherapy but reported that the education program helped assuage their concerns. Benefits included reduced financial costs, reduced travel time to hospital, less disruption to family life, and less stress for the child and family. No medication errors were reported during the evaluation period. An important feature of the program is the partnership approach, which ensures that parents' decision to enter the program is informed, appropriate for their situation, and centered on the needs of the child.

  15. Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Chih-Hsien Chang

    2014-01-01

    Full Text Available The pharmacokinetics of N,N-bis(2-mercapatoethly-N',N'-diethylenediamine (BMEDA, a molecule that can form a chelate with rhenium-188 (188Re to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles’ plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences. In addition, the pharmacokinetics of BMEDA was seen to be non-linear because the increase of mean AUC0–t and AUC0–∞ values tend to be greater than dose proportional while the mean Vss and CL values of BMEDA appeared to be dose dependent. The information on the pharmacokinetics of BMEDA generated from this study will serve as a basis to design appropriate pharmacology and toxicology studies for future human use.

  16. combined with either subcutaneous or intravenous administration of ...

    African Journals Online (AJOL)

    the time of sponge withdrawal, PMSG was administered either subcutaneously or ... Only the season of treatment had an effect on the percentage ... gestogen and Pregnant Mare Serum Gonackttrophin. (PMSG). ... artificial insemination.

  17. [Multiple sclerosis. Therapeutic nihilism is the wrong approach here].

    Science.gov (United States)

    Voltz, R; Goebels, N; Jarius, S; Hohlfeld, R

    2002-05-06

    The standard treatment for acute multiple sclerosis relapses continues to be the intravenous administration of high-dose methylprednisolone. For prophylactic purposes, immunomodulatory therapy with interferon beta or glatiramer acetate, immunoglobulins or azathioprine. Studies have shown that interferon beta not only reduces the frequency of relapses by one-third, but also significantly delays the second relapse, provided it is administrated early, that is, immediately following the first relapse. The reduction in the patient's quality of life caused by the illness can be appreciably improved by a whole series of symptomatic treatments. The ideal situation is a cooperative effort by an interdisciplinary team.

  18. 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 ...

  19. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ming-Fa Hsieh

    2010-12-01

    Full Text Available The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol (mPEG and one hydrophobic segment poly(ε‑caprolactone (PCL; which is synthesized by coupling of mPEG-PCL-OH and mPEG‑COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14 of DOX-loaded micelles as compared to multiple administrations of free DOX.

  20. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cuong, Nguyen-Van [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Department of Chemical Engineering, Ho Chi Minh City University of Industry, 12 Nguyen Van Bao St, Ho Chi Minh (Viet Nam); Jiang, Jian-Lin; Li, Yu-Lun [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Chen, Jim-Ray [Department of Pathology, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Jwo, Shyh-Chuan [Division of General Surgery, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Hsieh, Ming-Fa, E-mail: mfhsieh@cycu.edu.tw [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China)

    2010-12-28

    The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.

  1. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    International Nuclear Information System (INIS)

    Cuong, Nguyen-Van; Jiang, Jian-Lin; Li, Yu-Lun; Chen, Jim-Ray; Jwo, Shyh-Chuan; Hsieh, Ming-Fa

    2010-01-01

    The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX

  2. 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. 

  3. Intravenous fluid prescription practices among pediatric residents in Korea

    OpenAIRE

    Lee, Jiwon M.; Jung, Younghwa; Lee, Se Eun; Lee, Jun Ho; Kim, Kee Hyuck; Koo, Ja Wook; Park, Young Seo; Cheong, Hae Il; Ha, Il-Soo; Choi, Yong; Kang, Hee Gyung

    2013-01-01

    Purpose: Recent studies have established the association between hypotonic fluids administration and hospital-acquired hyponatremia in children, and have contended that hypotonic fluids be removed from routine practice. To assess current intravenous fluid prescription practices among Korean pediatric residents and to call for updated clinical-practice education Methods: A survey-based analysis was carried out. Pediatric residents at six university hospitals in Korea completed a survey consist...

  4. Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody.

    Science.gov (United States)

    Donahue, Renee N; Lepone, Lauren M; Grenga, Italia; Jochems, Caroline; Fantini, Massimo; Madan, Ravi A; Heery, Christopher R; Gulley, James L; Schlom, Jeffrey

    2017-01-01

    Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range of human tumor cells, and clinical studies have demonstrated anti-tumor activity versus a range of human cancers. This study was designed to investigate the effect on immune cell subsets in the peripheral blood of cancer patients prior to and following multiple administrations of avelumab. One hundred twenty-three distinct immune cell subsets in the peripheral blood of cancer patients ( n  = 28) in a phase I trial were analyzed by flow cytometry prior to and following one, three, and nine cycles of avelumab. Changes in soluble (s) CD27 and sCD40L in plasma were also evaluated. In vitro studies were also performed to determine if avelumab would mediate ADCC of PBMC. No statistically significant changes in any of the 123 immune cell subsets analyzed were observed at any dose level, or number of doses, of avelumab. Increases in the ratio of sCD27:sCD40L were observed, suggesting potential immune activation. Controlled in vitro studies also showed lysis of tumor cells by avelumab versus no lysis of PBMC from five donors. These studies demonstrate the lack of any significant effect on multiple immune cell subsets, even those expressing PD-L1, following multiple cycles of avelumab. These results complement prior studies showing anti-tumor effects of avelumab and comparable levels of adverse events with avelumab versus other anti-PD-1/PD-L1 MAbs. These studies provide the rationale to further exploit the potential ADCC mechanism of action of avelumab as well as other human IgG1 checkpoint

  5. 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.

  6. The effect of a clinical pharmacist-led training programme on intravenous medication errors : a controlled before and after study

    NARCIS (Netherlands)

    Nguyen, Huong; Pham, Hong-Tham; Vo, Dang-Khoa; Nguyen, Tuan-Dung; van den Heuvel, Edwin R.; Haaijer-Ruskamp, Flora M.; Taxis, Katja

    Background Little is known about interventions to reduce intravenous medication administration errors in hospitals, especially in low-and middle-income countries. Objective To assess the effect of a clinical pharmacist-led training programme on clinically relevant errors during intravenous

  7. Potential intravenous drug interactions in intensive care

    Directory of Open Access Journals (Sweden)

    Maiara Benevides Moreira

    Full Text Available Abstract OBJECTIVE To analyze potential intravenous drug interactions, and their level of severity associated with the administration of these drugs based on the prescriptions of an intensive care unit. METHOD Quantitative study, with aretrospective exploratory design, and descriptive statistical analysis of the ICU prescriptions of a teaching hospital from March to June 2014. RESULTS The sample consisted of 319 prescriptions and subsamples of 50 prescriptions. The mean number of drugs per patient was 9.3 records, and a higher probability of drug interaction inherent to polypharmacy was evidenced. The study identified severe drug interactions, such as concomitant administration of Tramadol with selective serotonin reuptake inhibitor drugs (e.g., Metoclopramide and Fluconazole, increasing the risk of seizures due to their epileptogenic actions, as well as the simultaneous use of Ranitidine-Fentanyl®, which can lead to respiratory depression. CONCLUSION A previous mapping of prescriptions enables the characterization of the drug therapy, contributing to prevent potential drug interactions and their clinical consequences.

  8. Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice

    International Nuclear Information System (INIS)

    Ikebe, E; Kawaguchi, A; Tezuka, K; Taguchi, S; Hirose, S; Matsumoto, T; Mitsui, T; Senba, K; Nishizono, A; Hori, M; Hasegawa, H; Yamada, Y; Ueno, T; Tanaka, Y; Sawa, H; Hall, W; Minami, Y; Jeang, K T; Ogata, M; Morishita, K; Hasegawa, H; Fujisawa, J; Iha, H

    2013-01-01

    In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression

  9. Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

    Science.gov (United States)

    Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

    2017-09-01

    Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  10. Toxicity evaluation of methoxy poly(ethylene oxide-block-poly(ε-caprolactone polymeric micelles following multiple oral and intraperitoneal administration to rats

    Directory of Open Access Journals (Sweden)

    Ziyad Binkhathlan

    2017-09-01

    Full Text Available Methoxy poly(ethylene oxide-block-poly(ɛ-caprolactone (PEO-b-PCL copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  11. Postarthroscopy analgesia using intraarticular levobupivacaine and intravenous dexketoprofen trometamol.

    Science.gov (United States)

    Sahin, Sevtap Hekimoglu; Memiş, Dilek; Celik, Erkan; Sut, Necdet

    2015-12-01

    The aim of this prospective study was to determine the efficacy of intraarticular levobupivacaine with and without intravenous dexketoprofen trometamol for postarthroscopy analgesia. Sixty patients who underwent arthroscopic knee surgery were randomly assigned to three treatment groups. When the surgical procedure was completed, patients received the following treatments: group I (n = 20) patients received 20 mL intraarticular normal saline and 2 mL intravenous dexketoprofen trometamol (50 mg); group II (n = 20) patients received 20 mL intraarticular 0.5 % levobupivacaine (100 mg) and 2 mL intravenous normal saline; and group III (n = 20) patients received 20 mL intraarticular 0.5 % levobupivacaine (100 mg) and 2 mL intravenous dexketoprofen trometamol (50 mg). The visual analogue scale (VAS) was used, and the total analgesic consumption was assessed at 1, 2, 4, 6, 12, and 24 h post-operatively. The VAS scores at 1, 2, 4, 6, 12, and 24 h post-operatively were significantly increased in group I and group II compared with group III (p dexketoprofen trometamol administration provided better pain relief and less analgesic requirement after arthroscopic knee surgery during the first 24 h than that induced by dexketoprofen alone or levobupivacaine intraarticular alone. II.

  12. Defining Persistent Hotspots: Areas That Fail to Decrease Meaningfully in Prevalence after Multiple Years of Mass Drug Administration with Praziquantel for Control of Schistosomiasis.

    Science.gov (United States)

    Kittur, Nupur; Binder, Sue; Campbell, Carl H; King, Charles H; Kinung'hi, Safari; Olsen, Annette; Magnussen, Pascal; Colley, Daniel G

    2017-12-01

    Preventive chemotherapy with praziquantel for schistosomiasis morbidity control is commonly done by mass drug administration (MDA). MDA regimen is usually based on prevalence in a given area, and effectiveness is evaluated by decreases in prevalence and/or intensity of infection after several years of implementation. Multiple studies and programs now find that even within well-implemented, multiyear, annual MDA programs there often remain locations that do not decline in prevalence and/or intensity to expected levels. We term such locations "persistent hotspots." To study and address persistent hotspots, investigators and neglected tropical disease (NTD) program managers need to define them based on changes in prevalence and/or intensity. But how should the data be analyzed to define a persistent hotspot? We have analyzed a dataset from an operational research study in western Tanzania after three annual MDAs using four different approaches to define persistent hotspots. The four approaches are 1) absolute percent change in prevalence; 2) percent change in prevalence; 3) change in World Health Organization guideline categories; 4) change (absolute or percent) in both prevalence and intensity. We compare and contrast the outcomes of these analyses. Our intent is to show how the same dataset yields different numbers of persistent hotspots depending on the approach used to define them. We suggest that investigators and NTD program managers use the approach most suited for their study or program, but whichever approach is used, it should be clearly stated so that comparisons can be made within and between studies and programs.

  13. Andrographis paniculata: Dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteers.

    Science.gov (United States)

    Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Puranajoti, Porranee; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Songvut, Phanit; Satayavivad, Jutamaad

    2016-12-24

    Andrographis paniculata is included in 'The National List of Essential Herbal Drugs A.D. 1999' of Thailand as an herbal drug for the treatment of common cold symptoms and non-infectious diarrhea. The therapeutic activities of A. paniculata are attributed to four major active diterpenoids: andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4). However, the pharmacokinetic studies in humans of this plant were performed after a single oral dose administration and reported the parameters related to be of only 1. This study aims to determine the pharmacokinetic parameters of four major active diterpenoids after multiple oral dose administration of A. paniculata capsules in healthy volunteers. The dissolution testing of these four diterpenoids was also performed. The dissolution testing of four major active diterpenoids was conducted in pH 1.2, pH 4.5, and pH 6.8 for 10-100min. The pharmacokinetic study of these active diterpenoids was designed as an open-label, multiple oral dose administration of A. paniculata capsules in 20 healthy Thai volunteers at 1:1 ratio of female and male. Each volunteer was given four A. paniculata capsules each time which contained 1, 2, 3, and 4 in the quantities of 32.64, 5.40, 3.60, and 3.84mg, respectively, three times a day for three consecutive days. On the fourth day, after the first dose of the day was administered, blood samples were collected at the predefined time points. The validated LC-MS/MS method was used to simultaneously determine the concentrations of these diterpenoids in the human plasma samples. The pharmacokinetic parameters of each active diterpenoid were determined. All four major active diterpenoids have been completely dissolved in the simulated pH of gastrointestinal tract within 60min of dissolution. The dissolution profiles were found to be highest in pH 6.8 and lowest in pH 1.2, especially for 3. In the pharmacokinetic study, although 1 was

  14. 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. 

  15. 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.

  16. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Holst; Werner, Mads Utke; Rosenkilde, Mette Marie

    2016-01-01

    BACKGROUND: The aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers. METHODS: The study was performed as a cohort crossover study. The volunteers received either 10 mg oral melatonin or 10 mg intravenous melatonin on two separate study days. Blood samples were...... collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were performed by "the method of residuals" and compartmental analysis. The pharmacokinetic variables: k a, t 1....../2 absorption, t max, C max, t 1/2 elimination, AUC 0-∞, and bioavailability were determined for oral melatonin. C max, t 1/2 elimination, V d, CL and AUC 0-∞ were determined for intravenous melatonin. RESULTS: Twelve male volunteers completed the study. Baseline melatonin plasma levels did not differ...

  17. Suppressive effect of glucocorticoids on TNF-alpha production is associated with their clinical effect in multiple sclerosis

    NARCIS (Netherlands)

    van Winsen, L.M.L.; Polman, C.H.; Dijkstra, C.D.; Tilders, F.J.H.; Uitdehaag, B.M.J.

    2010-01-01

    A reduced sensitivity to glucocorticoids can affect the clinical effect of treatment with high-dose intravenous methylprednisolone in multiple sclerosis. We prospectively studied 27 multiple sclerosis patients who were treated with intravenous methylprednisolone. Before and after treatment in vitro

  18. 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.

  19. 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.

  20. 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...

  1. Are referring clinicians aware of patients at risk from intravenous injection of iodinated contrast media?

    International Nuclear Information System (INIS)

    Konen, Eli; Konen, Osnat; Katz, Miriam; Levy, Yair; Rozenman, Judith; Hertz, Marjorie

    2002-01-01

    AIM: The purpose of our study was to assess the level of awareness of referring clinicians to populations at risk for complications of intravascular administration of iodinated contrast media. SUBJECTS AND METHODS: Two hundred and three physicians from three university hospitals completed an anonymous questionnaire regarding risk factors and contraindications to the intravenous administration of iodinated contrast media. The questionnaire included medical conditions with increased risk for anaphylactoid reaction (asthma, hay fever and food allergy) as well as chemotoxic (ischaemic heart disease, phaeochromocytoma and myasthenia gravis) adverse reactions, some with dependence on renal function (metformin treatment, diabetes mellitus and multiple myeloma). Two additional multiple-choice questions addressed pre-medication protocols and risk of nephrotoxicity in diabetic patients. RESULTS: Asthma, food allergy and hay fever were recognized as risk factors by 81·3%, 77·8% and 61·6% of respondents respectively, while ischaemic heart disease, phaeochromocytoma and myasthenia gravis were defined as such only by 9·8%, 30·0% and 28·6% respectively. Metformin treatment, diabetes mellitus and multiple myeloma, in the presence of normal renal function, were considered as risk factors by 46·3%, 38·9% and 58·1% of respondents respectively. One of the generally accepted pre-medication protocols was selected by 89·8%. The risk of nephrotoxicity in a diabetic patient was correctly assessed by 63·5% of respondents. CONCLUSION: We found a relatively high awareness among referring clinicians of a potential anaphylactoid reaction and nephrotoxicity due to iodinated contrast media. However, additional chemotoxic adverse reactions are less well known. Future efforts to improve communication between clinicians and radiologists should be focused in this direction. Konen, E. et al. (2002)

  2. Are referring clinicians aware of patients at risk from intravenous injection of iodinated contrast media?

    Energy Technology Data Exchange (ETDEWEB)

    Konen, Eli; Konen, Osnat; Katz, Miriam; Levy, Yair; Rozenman, Judith; Hertz, Marjorie

    2002-02-01

    AIM: The purpose of our study was to assess the level of awareness of referring clinicians to populations at risk for complications of intravascular administration of iodinated contrast media. SUBJECTS AND METHODS: Two hundred and three physicians from three university hospitals completed an anonymous questionnaire regarding risk factors and contraindications to the intravenous administration of iodinated contrast media. The questionnaire included medical conditions with increased risk for anaphylactoid reaction (asthma, hay fever and food allergy) as well as chemotoxic (ischaemic heart disease, phaeochromocytoma and myasthenia gravis) adverse reactions, some with dependence on renal function (metformin treatment, diabetes mellitus and multiple myeloma). Two additional multiple-choice questions addressed pre-medication protocols and risk of nephrotoxicity in diabetic patients. RESULTS: Asthma, food allergy and hay fever were recognized as risk factors by 81{center_dot}3%, 77{center_dot}8% and 61{center_dot}6% of respondents respectively, while ischaemic heart disease, phaeochromocytoma and myasthenia gravis were defined as such only by 9{center_dot}8%, 30{center_dot}0% and 28{center_dot}6% respectively. Metformin treatment, diabetes mellitus and multiple myeloma, in the presence of normal renal function, were considered as risk factors by 46{center_dot}3%, 38{center_dot}9% and 58{center_dot}1% of respondents respectively. One of the generally accepted pre-medication protocols was selected by 89{center_dot}8%. The risk of nephrotoxicity in a diabetic patient was correctly assessed by 63{center_dot}5% of respondents. CONCLUSION: We found a relatively high awareness among referring clinicians of a potential anaphylactoid reaction and nephrotoxicity due to iodinated contrast media. However, additional chemotoxic adverse reactions are less well known. Future efforts to improve communication between clinicians and radiologists should be focused in this direction. Konen

  3. 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.)

  4. 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.

  5. 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

  6. 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.

  7. Intravenous dipyridamole thallium-201 SPECT imaging methodology, applications, and interpretations

    International Nuclear Information System (INIS)

    Rockett, J.F.; Magill, H.L.; Loveless, V.S.; Murray, G.L.

    1990-01-01

    Dipyridamole TI-201 imaging is an ideal alternative to exercise TI-201 scintigraphy in patients who are unwilling or unable to perform maximum exercise stress. The use of intravenous dipyridamole, alone or in combination with exercise, has not been approved for clinical practice by the Food and Drug Administration. Once approval is granted, the test will become a widely used and important component of the cardiac work-up. The indications, methodology, side effects, and utility of dipyridamole cardiac imaging in the clinical setting are discussed and a variety of examples presented.59 references

  8. Intravenous Tranexamic Acid Decreases Allogeneic Transfusion Requirements in Periacetabular Osteotomy.

    Science.gov (United States)

    Bryan, Andrew J; Sanders, Thomas L; Trousdale, Robert T; Sierra, Rafael J

    2016-01-01

    Bernese (Ganz) periacetabular osteotomy is associated with significant blood loss and the need for perioperative transfusion. Tranexamic acid decreases blood loss and minimizes transfusion rates in total joint arthroplasty. However, no reports have described its use in patients undergoing Bernese periacetabular osteotomy. This study reports the use of intravenous tranexamic acid in these patients. The study included 137 patients (150 hips) who underwent isolated periacetabular osteotomy at a single institution between 2003 and 2014. Of these, 68 patients (75 hips) received intravenous tranexamic acid 1 g at the time of incision and 1 g at the time of closure. A group of 69 patients (75 hips) served as control subjects who underwent periacetabular osteotomy without administration of intravenous tranexamic acid. Thromboembolic disease was defined as deep venous thrombosis or pulmonary embolism occurring within 6 weeks of surgery. Outcomes measured included transfusion requirements, pre- and postoperative hemoglobin values, operative times, and thromboembolic disease rates. Aspirin was used as the thromboembolic prophylactic regimen in 95% of patients. The rate of allogeneic transfusion was 0 in the tranexamic acid group compared with 21% in the control group (P=.0001). No significant difference was found in the autologous cell salvage requirement (.96 vs 1.01; P=.43) or the thromboembolic disease rate between the tranexamic acid group and the control group (2.67% vs 1.33%; P=.31). The use of intravenous tranexamic acid led to a decreased transfusion requirement with no increased risk of thromboembolic disease in this contemporary cohort of patients undergoing periacetabular osteotomy. Copyright 2016, SLACK Incorporated.

  9. The prehospital intravenous access assessment: a prospective study on intravenous access failure and access delay in prehospital emergency medicine.

    Science.gov (United States)

    Prottengeier, Johannes; Albermann, Matthias; Heinrich, Sebastian; Birkholz, Torsten; Gall, Christine; Schmidt, Joachim

    2016-12-01

    Intravenous access in prehospital emergency care allows for early administration of medication and extended measures such as anaesthesia. Cannulation may, however, be difficult, and failure and resulting delay in treatment and transport may have negative effects on the patient. Therefore, our study aims to perform a concise assessment of the difficulties of prehospital venous cannulation. We analysed 23 candidate predictor variables on peripheral venous cannulations in terms of cannulation failure and exceedance of a 2 min time threshold. Multivariate logistic regression models were fitted for variables of predictive value (P0.6) of their respective receiver operating characteristic curve. A total of 762 intravenous cannulations were enroled. In all, 22% of punctures failed on the first attempt and 13% of punctures exceeded 2 min. Model selection yielded a three-factor model (vein visibility without tourniquet, vein palpability with tourniquet and insufficient ambient lighting) of fair accuracy for the prediction of puncture failure (AUC=0.76) and a structurally congruent model of four factors (failure model factors plus vein visibility with tourniquet) for the exceedance of the 2 min threshold (AUC=0.80). Our study offers a simple assessment to identify cases of difficult intravenous access in prehospital emergency care. Of the numerous factors subjectively perceived as possibly exerting influences on cannulation, only the universal - not exclusive to emergency care - factors of lighting, vein visibility and palpability proved to be valid predictors of cannulation failure and exceedance of a 2 min threshold.

  10. Comparison Efficacy of Topical Piroxicam Gel and Lidocaine with Intravenous Pethidine in Reducing Pain during ESWL

    Directory of Open Access Journals (Sweden)

    F Mohammad Alibeigi

    2011-06-01

    Full Text Available Introduction & Objective: ESWL is a non-invasive method of breaking stones, using acoustic shock waves. Shock waves cause temporary deep visceral pain and discomfort in entry therefore, administration of sedatives is necessary. The purpose of this study was to compare the effect of topical lidocaine and piroxicam gel with intravenous pethidine in reducing pain during ESWL. Materials & Methods: This clinical trial study was performed on 159 patients who referred to Ayatollah Kashani Hospital in Shahrkord for ESWL in 2009. Patients were randomly divided into three-groups. For the first group, intravenous pethidine (0.5 mg/kg alone was administered. The second group received topical piroxicam, and the third group received topical lidocaine in the area of flank for half an hour before ESWL. During the operation, those patients who had unbearable pain, received another 0.5 mg/kg of pethidine. Data was collected using MC Gill questionnaires and analyzed using the SPSS software, using parametric, nonparametric methods and Dunn's Multiple Comparisons tests. Results: The mean of pain scores in the first group (pethidine was 6.2 ± 6.9 while these scores were 3.2 ± 2 .7 and 3.9 ± 3.1 for the second (piroxicam gel and third group (lidocaine gel respectively. The differences in the mean score of pain was significant in the pethidine group compared to the other groups (P <0.05. The average pethidin consumption were 24 ± 16 mg for the first group (pethidine, 10 ± 13 mg for the second group (piroxicam gel, and 5 ± 9 mg for the third group (lidocaine gel. The mean difference was significant in pethidine treated group in comparison with other two groups (P < 0.05. Conclusion: The use of topical piroxicam or lidocaine reduces pain in patients after ESWL It also reduces the need for sedative drugs.

  11. 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 ...

  12. 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.

  13. 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.

  14. 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.

  15. Intravenous to oral conversion of fluoroquinolones: knowledge versus clinical practice patterns.

    Science.gov (United States)

    Conort, Ornella; Gabardi, Steven; Didier, Marie-Pauline; Hazebroucq, Georges; Cariou, Alain

    2002-04-01

    To assess the knowledge of prescribers regarding intravenous to oral conversions of fluoroquinolones, the frequency and time until conversion, and to compare prescriber knowledge with the data collected concerning the reasons stated for continuation of intravenous fluoroquinolones. Prospective chart review and questionnaire. Large teaching hospital in Paris, France. Fifty-one males and females. Data were collected on in-patients receiving intravenous fluoroquinolone for at least three days and hospitalized in one of six in-patient units. Patients receiving intravenous fluoroquinolone for less than three days were excluded. A questionnaire to assess the awareness of a potential conversion was distributed to those practitioners who had patients reviewed during the data-collection phase. The questionnaire revealed the ten most common reasons for continuing intravenous administration for more than three days. However, the physicians agreed that most patients should be converted as soon as possible. Practice patterns differed, with only 17 of 51 patients actually converted to oral therapy. In theory, the clinicians were aware of when to perform the conversion. However, in practice, the frequency of conversion was lower than optimum. Changes in clinical practice are needed to decrease the costs of intravenous therapy, without jeopardizing quality of care.

  16. Combined Intra-Articular and Intravenous Tranexamic Acid Reduces Blood Loss in Total Knee Arthroplasty

    DEFF Research Database (Denmark)

    Nielsen, Christian Skovgaard; Jans, Øivind; Ørsnes, Thue

    2016-01-01

    BACKGROUND: In total knee arthroplasty, both intravenous (IV) and intra-articular (IA) administration of tranexamic acid (TXA) have been shown to reduce blood loss in several randomized controlled trials, although routine use of systemic TXA is considerably more common. However, to our knowledge...

  17. 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...

  18. Is the routine use of intravenous contrast justified in the workup of ...

    African Journals Online (AJOL)

    The indications for the administration of intravenous contrast media to adult patients presenting with firsttime seizures and a normal pre-contrast study are not clear. A retrospective audit of such patients was done and compared with the post-contrast study. In our study sample of 205 patients all the post-contrast scans were ...

  19. 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

  20. Potential intravenous drug interactions in intensive care.

    Science.gov (United States)

    Moreira, Maiara Benevides; Mesquita, Maria Gefé da Rosa; Stipp, Marluci Andrade Conceição; Paes, Graciele Oroski

    2017-07-20

    To analyze potential intravenous drug interactions, and their level of severity associated with the administration of these drugs based on the prescriptions of an intensive care unit. Quantitative study, with aretrospective exploratory design, and descriptive statistical analysis of the ICU prescriptions of a teaching hospital from March to June 2014. The sample consisted of 319 prescriptions and subsamples of 50 prescriptions. The mean number of drugs per patient was 9.3 records, and a higher probability of drug interaction inherent to polypharmacy was evidenced. The study identified severe drug interactions, such as concomitant administration of Tramadol with selective serotonin reuptake inhibitor drugs (e.g., Metoclopramide and Fluconazole), increasing the risk of seizures due to their epileptogenic actions, as well as the simultaneous use of Ranitidine-Fentanyl®, which can lead to respiratory depression. A previous mapping of prescriptions enables the characterization of the drug therapy, contributing to prevent potential drug interactions and their clinical consequences. Analisar as potenciais interações medicamentosas intravenosas e seu grau de severidade associadas à administração desses medicamentos a partir das prescrições do Centro de Terapia Intensiva. Estudo quantitativo, tipologia retrospectiva exploratória, com análise estatística descritiva das prescrições medicamentosas do Centro de Terapia Intensiva de um Hospital Universitário, no período de março-junho/2014. A amostra foi composta de 319 prescrições e subamostras de 50 prescrições. Constatou-se que a média de medicamentos por paciente foi de 9,3 registros, e evidenciou-se maior probabilidade para ocorrência de interação medicamentosa inerente à polifarmácia. O estudo identificou interações medicamentosas graves, como a administração concomitante de Tramadol com medicamentos inibidores seletivos da recaptação da serotonina, (exemplo: Metoclopramida e Fluconazol

  1. Multiple Input - Multiple Output (MIMO) SAR

    Data.gov (United States)

    National Aeronautics and Space Administration — This effort will research and implement advanced Multiple-Input Multiple-Output (MIMO) Synthetic Aperture Radar (SAR) techniques which have the potential to improve...

  2. Cardiovascular effects of intravenous ghrelin infusion in healthy young men

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Andersen, Niels Holmark; Hansen, Troels Krarup

    2007-01-01

    Ghrelin infusion improves cardiac function in patients suffering from cardiac failure, and bolus administration of ghrelin increases cardiac output in healthy subjects. The cardiovascular effects of more continuous intravenous ghrelin exposure remain to be studied. We therefore studied the cardio......Ghrelin infusion improves cardiac function in patients suffering from cardiac failure, and bolus administration of ghrelin increases cardiac output in healthy subjects. The cardiovascular effects of more continuous intravenous ghrelin exposure remain to be studied. We therefore studied...... the cardiovascular effects of a constant infusion of human ghrelin at a rate of 5 pmol/kg per minute for 180 min. Fifteen healthy, young (aged 23.2 ± 0.5 yr), normal-weight (23.0 ± 0.4 kg/m2) men volunteered in a randomized double-blind, placebo-controlled crossover study. With the subjects remaining fasting, peak...... myocardial systolic velocity S′, tissue tracking TT, left ventricular ejection fraction EF, and endothelium-dependent flow-mediated vasodilatation were measured. Ghrelin infusion increased S′ 9% (P = 0.002) and TT 10% (P

  3. 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.

  4. Assistance algorithm of nursing for amiodarone intravenous infusion

    Directory of Open Access Journals (Sweden)

    Francimar Tinoco de Oliveira

    2014-12-01

    Full Text Available This study aimed at identifying scientific publication on phlebitis caused by amiodarone and proposes a nursing care algorithm for interventions in intravenous amiodarone administration grounded in the Infusion Nursing Society and the Center for Disease Control and Prevention. It is a descriptive study mediated by integrative review in MedLine, LILACS, IBECS, BDENF, Cochrane Library and Scielo bases, published from 2006 to 2013. The sample consisted of nine articles. The evidence pointed the incidence of phlebitis due to the infusion of amiodarone and the need to control this event. The algorithm proposed shows the materials to be used and the procedure of drug administration in order to minimize injury. Besides subsidizing the development of future studies, this algorithm also promotes the incorporation of the best recommendation for the interventionist clinical practice.

  5. A survey of critical care nurses' practices and perceptions surrounding early intravenous antibiotic initiation during septic shock.

    Science.gov (United States)

    Roberts, Russel J; Alhammad, Abdullah M; Crossley, Lindsay; Anketell, Eric; Wood, LeeAnn; Schumaker, Greg; Garpestad, Erik; Devlin, John W

    2017-08-01

    Delays in antibiotic administration after severe sepsis recognition increases mortality. While physician and pharmacy-related barriers to early antibiotic initiation have been well evaluated, those factors that affect the speed by which critical care nurses working in either the emergency department or the intensive care unit setting initiate antibiotic therapy remains poorly characterized. To evaluate the knowledge, practices and perceptions of critical care nurses regarding antibiotic initiation in patients with newly recognised septic shock. A validated survey was distributed to 122 critical care nurses at one 320-bed academic institution with a sepsis protocol advocating intravenous(IV) antibiotic initiation within 1hour of shock recognition. Among 100 (82%) critical care nurses responding, nearly all (98%) knew of the existence of the sepsis protocol. However, many critical care nurses stated they would optimise blood pressure [with either fluid (38%) or both fluid and a vasopressor (23%)] before antibiotic initiation. Communicated barriers to rapid antibiotic initiation included: excessive patient workload (74%), lack of awareness IV antibiotic(s) ordered (57%) or delivered (69%), need for administration of multiple non-antibiotic IV medications (54%) and no IV access (51%). Multiple nurse-related factors influence IV antibiotic(s) initiation speed and should be incorporated into sepsis quality improvement efforts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Effects of Rapid Intravenous Rehydration in Children With Mild-to-Moderate Dehydration.

    Science.gov (United States)

    Janet, Sophie; Molina, Juan Carlos; Marañón, Rafael; García-Ros, Marta

    2015-08-01

    New guidelines for "rapid or ultrarapid" intravenous rehydration are being developed in different emergency departments. These new guidelines propose a faster administration of fluids and electrolytes than in traditional protocols. However, there is still insufficient evidence to establish a standard protocol. Our objective was to determine the effects of an outpatient rapid intravenous rehydration regimen based on the administration of 0.9% saline + 2.5% dextrose, at a rate of 20 mL/kg per hour for 2 hours, in children with mild-to-moderate isonatremic dehydration resulting from acute gastroenteritis. We performed a 2-institution, prospective, observational, descriptive study. Eighty-three patients were included in the study. All patients underwent a first evaluation, including physical examination, laboratory tests, and assessment of clinical degree of dehydration. After this initial evaluation, all children received our intravenous rehydration regimen. A second evaluation including the same items as in the first one was made after in all the children. Intravenous rehydration was successful in 69 patients (83.1%). It failed in 14 patients (16.8%), who required hospitalization because of persistent vomiting in 9 patients and poor general appearance in 5 patients. After intravenous rehydration, we observed a statistically significant decrease in the levels of ketonemia and uremia and in the Gorelick scale score. However, no significant changes were observed in sodium, chloride, potassium, and osmolarity values. We conclude that, in children with mild-to-moderate dehydration, the administration of 20 mL/kg per hour for 2 hours of 0.9% saline solution + 2.5% glucose improved clinical scores and may be used as an alternative and safe way for intravenous rehydration.

  7. Transient angioedema of small bowel secondary to intravenous iodinated contrast medium

    Directory of Open Access Journals (Sweden)

    Kirankumar N Kulkarni

    2014-01-01

    Full Text Available We report the clinical details and imaging findings of a case of transient angioedema of the small bowel following intravenous administration of non-ionic iodinated contrast material in a 17 year old female with no predisposing risk factors. Findings included long segment, symmetric, circumferential, low-density, bowel wall thickening involving the duodenum, jejunum, and most of the ileum on computed tomography scan obtained at 7 min following intravenous contrast material injection. This entity is self-limiting with a favourable clinical outcome and requires no specific treatment but only aggressive clinical monitoring.

  8. 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.

  9. Pharmacokinetics difference of multiple active constituents from decoction and maceration of Fuzi Xiexin Tang after oral administration in rat by UPLC-MS/MS.

    Science.gov (United States)

    Zhang, Qian; Ma, Yue-ming; Wang, Zheng-tao; Wang, Chang-hong

    2014-04-01

    Fuzi Xiexin Tang (FXT) is a classic traditional Chinese medicine formula which has been employed in clinical for more than 1800 years. The distinctive preparation method (maceration) recorded in ancient time is different from one in modern clinical practice (decoction). Aim of this study is to investigate the pharmacokinetic difference of alkaloids, flavones and anthraquinones in rats after oral administration of decoction of FXT (DFXT, 30gkg(-1)), maceration of FXT (MFXT, 30gkg(-1)) and decoction of Aconiti Lateralis Radix Preparata (DAR, 6gkg(-1)) by a validated UPLC-MS/MS method. Plasma concentrations and pharmacokinetic parameters of 16 active constituents (aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypaconine, benzoylmesaconine, berberine, palmatine, jatrorrhizine, coptisine, baicalin, wogonin, wogonoside, emodin, aloe-emodin, rhein) in rat were quantified and compared. Different preparative methods resulted in significant difference on exposure and pharmacokinetic characteristics of alkaloids, flavones and anthraquinones from FXT, especially protoberberine alkaloids. Concentrations of monoester-diterpenoid alkaloids were below the LOD in rat plasma after administration of DFXT and MFXT because of the existence of other three herbs from FXT. Maceration could decrease the absorption of flavones while increased the absorption of anthraquinones. Cmax of emodin and rhein were 3.1 and 10.3 times increased, while eliminations of these two constituents were 8.0 and 19.0 times slower after administration of MFXT. Bioavailability of both flavones and anthraquinones increased after administration of MFXT, especially emodin and rhein increasing as much as 13.5 and 20.7 times. Herb-herb interaction between DAR and other three herbs from FXT significantly influenced the exposure of aconitum alkaloids. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Effect of intravenous magnesium sulphate or dexamethasone as adjuvants to sevoflurane anesthesia to prevent delirium during primary cleft palate repair, controlled randomized blind study

    Directory of Open Access Journals (Sweden)

    M. Elsonbaty

    2017-01-01

    Conclusion: Co-administration of intravenous magnesium sulphate or dexamethasone with to sevoflurane anesthesia during primary cleft palate repair provides more vital hemodynamic state and decrease in postoperative vomiting and delirium when compared with control group.

  11. Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology.

    Science.gov (United States)

    Xia, Chun-Fang; Zhang, Yufeng; Zhang, Yun; Boado, Ruben J; Pardridge, William M

    2007-12-01

    The effective delivery of short interfering RNA (siRNA) to brain following intravenous administration requires the development of a delivery system for transport of the siRNA across the brain capillary endothelial wall, which forms the blood-brain barrier in vivo. siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidin-biotin technology. The siRNA was mono-biotinylated on either terminus of the sense strand, in parallel with the production of a conjugate of the targeting MAb and streptavidin. Rat glial cells (C6 or RG-2) were permanently transfected with the luciferase gene, and implanted in the brain of adult rats. Following the formation of intra-cranial tumors, the rats were treated with a single intravenous injection of 270 microg/kg of biotinylated siRNA attached to a transferrin receptor antibody via a biotin-streptavidin linker. The intravenous administration of the siRNA caused a 69-81% decrease in luciferase gene expression in the intracranial brain cancer in vivo. Brain delivery of siRNA following intravenous administration is possible with siRNAs that are targeted to brain with the combined use of receptor specific antibody delivery systems and avidin-biotin technology.

  12. Multiple intracerebral lesions in a young male

    African Journals Online (AJOL)

    of his brain showed multiple ill-defined and nodular enhancing lesions in bilateral supratentorial and ... Toxoplasmosis occurs in patients with CD4 T cell ... or from undercooked meat. ... Yoganathan K. A “brain tumor” in an intravenous.

  13. 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

  14. The pre-hospital administration of tranexamic acid to patients with multiple injuries and its effects on rotational thrombelastometry: a prospective observational study in pre-hospital emergency medicine.

    Science.gov (United States)

    Kunze-Szikszay, Nils; Krack, Lennart A; Wildenauer, Pauline; Wand, Saskia; Heyne, Tim; Walliser, Karoline; Spering, Christopher; Bauer, Martin; Quintel, Michael; Roessler, Markus

    2016-10-10

    Hyperfibrinolysis (HF) is a major contributor to coagulopathy and mortality in trauma patients. This study investigated (i) the rate of HF during the pre-hospital management of patients with multiple injuries and (ii) the effects of pre-hospital tranexamic acid (TxA) administration on the coagulation system. From 27 trauma patients with pre-hospital an estimated injury severity score (ISS) ≥16 points blood was obtained at the scene and on admission to the emergency department (ED). All patients received 1 g of TxA after the first blood sample was taken. Rotational thrombelastometry (ROTEM) was performed for both blood samples, and the results were compared. HF was defined as a maximum lysis (ML) >15 % in EXTEM. The median (min-max) ISS was 17 points (4-50 points). Four patients (15 %) had HF diagnosed via ROTEM at the scene, and 2 patients (7.5 %) had HF diagnosed via ROTEM on admission to the ED. The median ML before TxA administration was 11 % (3-99 %) vs. 10 % after TxA administration (4-18 %; p > 0.05). TxA was administered 37 min (10-85 min) before ED arrival. The ROTEM results before and after TxA administration did not significantly differ. No adverse drug reactions were observed after TxA administration. HF can be present in severely injured patients during pre-hospital care. Antifibrinolytic therapy administered at the scene is a significant time saver. Even in milder trauma fibrinogen can be decreased to critically low levels. Early administration of TxA cannot reverse or entirely stop this decrease. The pre-hospital use of TxA should be considered for severely injured patients to prevent the worsening of trauma-induced coagulopathy and unnecessarily high fibrinogen consumption. ClinicalTrials.gov ID NCT01938768 (Registered 5 September 2013).

  15. 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.

  16. 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.

  17. Onset and Duration of Intravenous and Intraosseous Rocuronium in Swine

    Directory of Open Access Journals (Sweden)

    Michael Loughren

    2014-03-01

    Full Text Available Introduction: The intraosseous (IO route has become a popular method to gain access to the peripheral circulation in emergency situations. Despite little supporting data, it is generally believed that IO absorption is immediate and equivalent to the intravenous (IV route. It is important to determine if rocuronium can effectively be administered by the IO route. The aim of the study was to determine and compare the onset and duration of rocuronium when administered via the IO and IV routes in a normovolemic pig model. Methods: We recorded electromyographic (EMG data following tibial IO and peripheral IV administration of rocuronium (1.2 mg/kg in 10 swine weighing between 56 and 71 Kg. We transformed data were transformed to percent of baseline, determined onset and recovery characteristics. Results: The onset EMG-time profiles for IO and IV administration were very similar: tibial IO compared to IV administration did not statistically alter the onset of paralysis. The IO group took statistically longer than the IV group to return to 50 (p=0.042, 75 (p=0.034 and 95 (p=0.036 percent of baseline activity. Conclusion: The duration of effect is statistically longer after IO administration but is more of an academic interest than a clinical concern. The results of this study suggest that rocuronium can effectively be administered via the IO route without the need for dose adjustments. [West J Emerg Med. 2014;15(2:241-245.

  18. Onset and Duration of Intravenous and Intraosseous Rocuronium in Swine

    Science.gov (United States)

    Loughren, Michael; Banks, Sarah; Naluan, Carleo; Portenlanger, Paul; Wendorf, Arthur; Johnson, Don

    2014-01-01

    Introduction The intraosseous (IO) route has become a popular method to gain access to the peripheral circulation in emergency situations. Despite little supporting data, it is generally believed that IO absorption is immediate and equivalent to the intravenous (IV) route. It is important to determine if rocuronium can effectively be administered by the IO route. The aim of the study was to determine and compare the onset and duration of rocuronium when administered via the IO and IV routes in a normovolemic pig model. Methods We recorded electromyographic (EMG) data following tibial IO and peripheral IV administration of rocuronium (1.2 mg/kg) in 10 swine weighing between 56 and 71 Kg. We transformed data were transformed to percent of baseline, determined onset and recovery characteristics. Results The onset EMG-time profiles for IO and IV administration were very similar: tibial IO compared to IV administration did not statistically alter the onset of paralysis. The IO group took statistically longer than the IV group to return to 50 (p=0.042), 75 (p=0.034) and 95 (p=0.036) percent of baseline activity. Conclusion The duration of effect is statistically longer after IO administration but is more of an academic interest than a clinical concern. The results of this study suggest that rocuronium can effectively be administered via the IO route without the need for dose adjustments. PMID:24672619

  19. Cost-Effectiveness of Intravenous Proton Pump Inhibitors in High-Risk Bleeders

    Directory of Open Access Journals (Sweden)

    Sander Veldhuyzen van Zanten

    2004-01-01

    Full Text Available There is unequivocal evidence that proton pump inhibitors (PPIs are currently the most effective acid suppressive agents available. Intravenous (IV formulations have been developed, although only IV pantoprazole is available in Canada. In patients presenting with serious upper gastrointestinal (GI bleeding due to duodenal or gastric ulcers, it has always been believed that IV administration of acid-lowering agents would improve clinical outcomes. The reason behind this thinking is twofold. First, there is in vitro evidence that formed clots are more stable at or near neutral pH (1. Second, by administering the agent intravenously, suppression of acid production is achieved much more quickly, thereby promoting more rapid healing of the ulcer and reducing the risk of persistent or recurrent bleeding. Interestingly and surprisingly, however, the data for intravenous H2-blockers have been disappointing (2. This failure to demonstrate clinical benefit has never been fully explained.

  20. Enzymatic assays for detecting lactose and sucrose in urine to reveal intravenous drug abuse with emphasis on buprenorphine.

    Science.gov (United States)

    Keltanen, T; Mariottini, C; Walta, A M; Rahikainen, A L; Ojanperä, I

    2017-06-01

    Buprenorphine and methadone are commonly used medications for opioid maintenance treatment (OMT), using sublingual and oral administration, respectively. Although beneficial for OMT, these drugs can also be abused by intravenous administration. In intravenous abuse cases, the adjuvants lactose and sucrose are excreted in urine without hydrolysis to monosaccharides, since there are no disaccharidases in the blood. We validated enzymatic methods for the analysis of lactose and sucrose in urine. The analytical performance of both assays was considered appropriate for detecting intravenous drug abuse. The principle was proven by analyzing 93 postmortem (PM) urine samples for lactose, following comprehensive toxicological drug screening. In addition, 32 clinical urine samples from potential drug abusers were analyzed to assess the effect of PM changes on the assay. The mean level of lactose was low in clinical samples and relatively low in PM samples in which no drugs were found. Markedly elevated levels were seen in many of the buprenorphine positive samples, suggesting intravenous administration. Enzymatic methods could provide a simple and cost effective way to assess the intravenous administration of OMT drugs or drugs of abuse. Very high levels of glucose in urine may interfere with the assays. Furthermore, other causes for elevated urine disaccharides, such as hypolactasia and increased intestinal permeability, need to be considered in the interpretation of the results. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Intravenous fluid prescription practices among pediatric residents in Korea

    Directory of Open Access Journals (Sweden)

    Jiwon M. Lee

    2013-07-01

    Full Text Available Purpose: Recent studies have established the association between hypotonic fluids administration and hospital-acquired hyponatremia in children, and have contended that hypotonic fluids be removed from routine practice. To assess current intravenous fluid prescription practices among Korean pediatric residents and to call for updated clinical-practice education Methods: A survey-based analysis was carried out. Pediatric residents at six university hospitals in Korea completed a survey consisting of four questions. Each question supposed a unique scenario in which the respondents were to prescribe either a hypotonic or an isotonic fluid for the patient. Results: Ninety-one responses were collected and analyzed. In three of the four scenarios, a significant majority prescribed the hypotonic fluids (98.9%, 85.7%, and 69.2%, respectively. Notably, 69.2% of the respondents selected the hypotonic fluids for postoperative management. Almost all (96.7% selected the isotonic fluids for hydration therapy. Conclusion: In the given scenarios, the majority of Korean pediatric residents would prescribe a hypotonic fluid, except for initial hydration. The current state of pediatric fluid management, notably, heightens the risk of hospital-acquired hyponatremia. Updated clinical practice education on intravenous fluid prescription, therefore, is urgently required.

  2. Intravenous fluid prescription practices among pediatric residents in Korea.

    Science.gov (United States)

    Lee, Jiwon M; Jung, Younghwa; Lee, Se Eun; Lee, Jun Ho; Kim, Kee Hyuck; Koo, Ja Wook; Park, Young Seo; Cheong, Hae Il; Ha, Il-Soo; Choi, Yong; Kang, Hee Gyung

    2013-07-01

    Recent studies have established the association between hypotonic fluids administration and hospital-acquired hyponatremia in children. The present paper investigated the pattern of current practice in intravenous fluid prescription among Korean pediatric residents, to underscore the need for updated education. A survey-based analysis was carried out. Pediatric residents at six university hospitals in Korea completed a survey consisting of four questions. Each question proposed a unique scenario in which the respondents had to prescribe either a hypotonic or an isotonic fluid for the patient. Ninety-one responses were collected and analyzed. In three of the four scenarios, a significant majority prescribed the hypotonic fluids (98.9%, 85.7%, and 69.2%, respectively). Notably, 69.2% of the respondents selected the hypotonic fluids for postoperative management. Almost all (96.7%) selected the isotonic fluids for hydration therapy. In the given scenarios, the majority of Korean pediatric residents would prescribe a hypotonic fluid, except for initial hydration. The current state of pediatric fluid management, notably, heightens the risk of hospital-acquired hyponatremia. Updated clinical practice education on intravenous fluid prescription, therefore, is urgently required.

  3. Cloxacillin distribution in the rabbit eye after intravenous injection

    International Nuclear Information System (INIS)

    Salminen, L.

    1978-01-01

    Distribution of isotopically labelled and intravenously injected cloxacillin was studied in the rabbit eye. The antibiotic concentration determined by liquid scintillation counting proved to be a reliable measure of the total antibiotic concentration when controlled by microbiological assay. In the rabbit eye after an intravenous injection of 50 mg/kg of cloxacillin sodium, longlasting antibiotic concentration regarded as therapeutic against penicillinase producing staphylococci was obtained in all vascularized ocular structures and in the cornea. The antibiotic present in the iris and ciliary body, and in the retina and choroid preparations, proved to be partly intravascular, whereas it penetrated better into the extravascular tissue compartment of the sclera and limbal area. Cloxacillin failed to achieve a therapeutic antibiotic concentration in the vitreous body and in the lens. Administration of probenecid had an enhancing effect on ocular cloxacillin concentration allowing improved drug diffusion into the eye by means of an elevated plasma concentration. No specific ocular effect of probenecid was noticed. Therapeutic concentration of cloxacillin in the aqueous humour, otherwise barely achieved, was more satisfactorily obtained with a previous injection of probenecid. (author)

  4. 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)

  5. Intermittent Oral Versus Intravenous Alfacalcidol in Dialysis Patients

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    Mitwalli Ahmed

    2000-01-01

    Full Text Available Patients with end-stage renal failure (ESRF on maintenance dialysis, commonly develop secondary hyperparathyroidism and renal osteodystrophy (ROD. Alfacalcidol, taken orally or administered intravenously, is known to reverse these complications. In this study, 19 ESRF patients, who were on dialysis (13 on hemodialysis and six on peritoneal dialysis for longer than six months and having serum parathormone levels at least four times normal and serum calcium less than 2.1 mmol/L, were randomly allocated to treatment with oral or intravenous (i.v. alfacalcidol for a period of 12 months. There were six patients on hemodialysis (HD and three on peritoneal dialysis (PD in the oral treatment group while in the i.v. group there were seven patients on HD and three on PD. Clinical and serial biochemical assessments showed no statistically significant difference between the orally- and i.v.-treated patients in terms of suppressing secondary hyperparathyroidism and osteodystrophy. However, patients with features of mild ROD on bone histology, had more satisfactory changes in biochemistry when compared to others. Our results further support the use of intermittent oral alfacalcidol in ESRF patients because of its cost effectiveness, ease of administration and convenience, especially for peritoneal dialysis patients.

  6. Spongiform leucoencephalopathy following intravenous heroin abuse: Radiological and histopathological findings

    International Nuclear Information System (INIS)

    Robertson, A.S.; Jain, S.; O'Neil, R.A.

    2001-01-01

    A case of spongiform leucoencephalopathy in a known intravenous heroin abuser is presented. To our knowledge, this is the only case of heroin-related spongiform leucoencephalopathy reported in Australia. The relationship to intravenous rather than inhaled heroin is particularly unusual with only one other possible case documented in the literature. The imaging and histopathological findings are described. Neurological examination revealed disorientation in time and place, memory loss and cognitive impairment but no focal signs. Biochemical and haematological profiles were normal. Viral serology was positive for hepatitis C but negative for hepatitis B and human immunodeficiency virus (HIV). Cerebral CT revealed diffuse symmetrical hypodensity of the cerebral white matter. The ventricles and subarachnoid spaces were of normal size. Magnetic resonance imaging showed diffuse symmetrical signal abnormality in the cerebral white matter. These changes were hyperintense on proton density, T2-weighted, modified T2-weighted (FLAIR) and diffusion-weighted images. T1 -weighted scans showed corresponding hypointensity. There was no enhancement after intravenous gadolinium. Cerebral spinal fluid (CSF) specimens were negative for a variety of virological, immunological and bacteriological markers. No viral or bacterial growth was demonstrated. Oligoclonal bands for multiple sclerosis and Protein 134 for Wilson's disease were negative. Right frontal brain biopsy showed spongiform white matter and degenerative change with prominent fibrous gliosis. In severely affected areas, loss of normal myelin staining and axonal loss were present, accompanied by scattered foamy macrophages. Loss of oligodendroglial nuclei was also present. There was no evidence of inflammation or progressive multifocal leucoencephalopathy. No bacteria or virus particles were seen on electron microscopic examination of the brain tissue. Following the biopsy, the patient discharged himself from hospital and the

  7. Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody

    OpenAIRE

    Donahue, Renee N.; Lepone, Lauren M.; Grenga, Italia; Jochems, Caroline; Fantini, Massimo; Madan, Ravi A.; Heery, Christopher R.; Gulley, James L.; Schlom, Jeffrey

    2017-01-01

    Background Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range...

  8. Identification and Pharmacokinetics of Multiple Potential Bioactive Constituents after Oral Administration of Radix Astragali on Cyclophosphamide-Induced Immunosuppression in Balb/c Mice

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    Menghua Liu

    2015-03-01

    Full Text Available Radix Astragali (RA is one of the commonly-used traditional Chinese medicines (TCMs with an immunomodulatory effect confirmed in the clinic. In order to better understand the material basis for the therapeutic effects, this study was to investigate the absorbed components and their pharmacokinetic profile after oral administration of RA on cyclophosphamide-induced immunosuppression in Balb/c mice. As a result, 51 compounds in RA extract and 31 prototype compounds with nine metabolites were detected in mice plasma by the ultra-fast liquid chromatography (UFLC-DAD-Q-TOF-MS/MS method. The pharmacokinetic parameters of five main constituents, including calycosin-7-O-glucoside, ononin, calycosin, formononetin and astragaloside IV, were obtained using HPLC-MS/MS. These results offered useful information for research on the pharmacological mechanism of RA and for its further development.

  9. The adverse effects of inadvertent intraoperative intravenous ...

    African Journals Online (AJOL)