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Sample records for intravenous humanized anti-muc1

  1. Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti-Ga chelate antibodies and immunoscintigraphy with PET.

    PubMed

    Schuhmacher, J; Klivényi, G; Kaul, S; Henze, M; Matys, R; Hauser, H; Clorius, J

    2001-10-01

    We recently demonstrated the feasibility of combining enhanced tumor-to-tissue contrast and PET imaging for immunoscintigraphic tumor localization in pancreas and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a multistep targeting technique that consists of the sequential administration of an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the antihapten binding sites of the BS-MAb that remains in circulation, and a low molecular weight Ga chelate, labeled with the positron emitter 68Ga, which serves as the hapten. To evaluate the efficacy of this pretargeting technique for breast cancer localization, we synthesized a BS-MAb from the F(ab')(2) fragments of the anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a bifunctional chemical linker. The BS-MAb was tested for its affinity and its biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding of the BS-MAb for mammary carcinoma cells was low (1.2 x 10(7) M(-1)) while the binding capacity of cells was high (8.4 x 10(6) BS-MAbs per cell). Tumor uptake of the 67Ga labeled chelate in pretargeted animals was to 5.8 +/- 0.8% iD/g resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares with a ratio of 0.65 and 0.85 obtained with 125I-labeled native 12H12 at 24h and 48h postinjection. No difference in the tumor uptake of both the 68Ga and 67Ga labeled chelate was observed. PET imaging of mice, started 1h postinjection of the 68Ga chelate, clearly visualized all tumors.

  2. Development of a hyperimmune anti-MUC-1 single chain antibody fragments phage display library for targeting breast cancer.

    PubMed

    Winthrop, M D; DeNardo, S J; DeNardo, G L

    1999-10-01

    Radioimmunotherapy (RIT) has demonstrated potential for improving clinical cancer therapy. Optimizing the approach has proven difficult thus far. Antibody phage display libraries provide unique molecules that could improve RIT. A phage display library of single chain antibody fragments (scFv) against the MUC-1 mucin molecule, which is expressed on 90% of human breast cancers, was produced from the spleen cells of MUC-1 hyperimmunized BALB/c mice. Increased serum IgG levels, 15 times baseline, were detected following the third immunization. RNA from the spleen cells was isolated, cDNA was made, and variable heavy and variable light immunoglobulin chain gene regions were amplified using PCR technology. The variable heavy and variable light chain gene regions were combined with a flexible linker, ligated into the pCANTAB 5E phagemid vector, and electroporated into TG1 Escherichia coli cells. A library of 10(7) initial colonies was compiled. Forty-six of 288 colonies screened for reactivity demonstrated binding to MUC-1-expressing MCF-7 breast cancer cell membrane fragments. Anti-MUC-1 library diversity evaluated by BstNI digest demonstrated that 52% of the anti-MUC-1 scFv binding MCF-7 possessed individual banding patterns representative of approximately 5 x 10(5) colonies likely able to recognize distinct epitopes present on MUC-1 positive human breast cancers. In summary, the anti-MUC-1 scFv antibody phage library contains diverse scFv molecules, which should provide unique characteristics and epitope recognition. These molecules will be used in the development of pretargeting RIT strategies designed to improve the clinical outcome of patients with breast cancer.

  3. Anti-MUC1 antibody inhibits EGF receptor signaling in cancer cells

    SciTech Connect

    Hisatsune, Akinori; Nakayama, Hideki; Kawasaki, Mitsuru; Horie, Ichiro; Miyata, Takeshi; Isohama, Yoichiro; Kim, Kwang Chul; Katsuki, Hiroshi

    2011-02-18

    Research highlights: {yields} We identified changes in the expression and function of EGFR by anti-MUC1 antibody. {yields} An anti-MUC1 antibody GP1.4 decreased EGFR from cell surface by internalization. {yields} GP1.4 specifically inhibited ERK signaling triggered EGF-EGFR signaling pathway. {yields} Internalization of EGFR was dependent on the presence of MUC1 on cell surface. {yields} GP1.4 significantly inhibited EGF-dependent cancer cell proliferation and migration. -- Abstract: MUC1 is a type I transmembrane glycoprotein aberrantly overexpressed in various cancer cells. High expression of MUC1 is closely associated with cancer progression and metastasis, leading to poor prognosis. We previously reported that MUC1 is internalized by the binding of the anti-MUC1 antibody, from the cell surface to the intracellular region via the macropinocytotic pathway. Since MUC1 is closely associated with ErbBs, such as EGF receptor (EGFR) in cancer cells, we examined the effect of the anti-MUC1 antibody on EGFR trafficking. Our results show that: (1) anti-MUC1 antibody GP1.4, but not another anti-MUC1 antibody C595, triggered the internalization of EGFR in pancreatic cancer cells; (2) internalization of EGFR by GP1.4 resulted in the inhibition of ERK phosphorylation by EGF stimulation, in a MUC1 dependent manner; (3) inhibition of ERK phosphorylation by GP1.4 resulted in the suppression of proliferation and migration of pancreatic cancer cells. We conclude that the internalization of EGFR by anti-MUC1 antibody GP1.4 inhibits the progression of cancer cells via the inhibition of EGFR signaling.

  4. Anti-MUC1 nano-aptamers for triple-negative breast cancer imaging by single-photon emission computed tomography in inducted animals: initial considerations

    PubMed Central

    Santos do Carmo, Fagner; Ricci-Junior, Eduardo; Cerqueira-Coutinho, Cristal; Albernaz, Marta de Souza; Bernardes, Emerson Soares; Missailidis, Sotiris; Santos-Oliveira, Ralph

    2017-01-01

    The early and specific detection of tumors remains a barrier in oncology, especially in cases such as the triple-negative breast cancer (TNBC). To address this gap, aptamers have found an important application in the recognition of tumor biomarkers such as mucin 1 (MUC1). However, there are still some difficulties in the use of aptamer, as their rapid biological clearance makes their use as drugs limited. In this study, the anti-MUC1 aptamer was used as a drug delivery system (DDS) for a radioactive polymeric nanoparticle (NP) in the imaging of TNBCs. Thus, poly(lactic-co-glycolic acid) NPs loaded with the anti-MUC1 aptamer and labeled with technetium-99m were used for a biodistribution study and imaging of TNBC. The results confirmed that the NP was successfully obtained, with a mean size of 262 nm, according to the dynamic light scattering data. The biodistribution assay in induced animal models with TNBC showed that although there was a high capture by intestine (>30%), the DDS developed had a high tumor uptake (5%) and with great in vivo imaging properties, corroborating the possibility of use of this DDS as an imaging drug for TNBC. PMID:28053523

  5. Deciphering the Non-Equivalence of Serine and Threonine O-Glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti-MUC1 Antibody**

    PubMed Central

    Martínez-Sáez, Nuria; Castro-López, Jorge; Valero-González, Jessika; Madariaga, David; Compañón, Ismael; Somovilla, Víctor J; Salvadó, Míriam; Asensio, Juan L; Jiménez-Barbero, Jesús; Avenoza, Alberto; Busto, Jesús H; Bernardes, Gonçalo J L; Peregrina, Jesús M; Hurtado-Guerrero, Ramón; Corzana, Francisco

    2015-01-01

    The structural features of MUC1-like glycopeptides bearing the Tn antigen (α-O-GalNAc-Ser/Thr) in complex with an anti MUC-1 antibody are reported at atomic resolution. For the α-O-GalNAc-Ser derivative, the glycosidic linkage adopts a high-energy conformation, barely populated in the free state. This unusual structure (also observed in an α-S-GalNAc-Cys mimic) is stabilized by hydrogen bonds between the peptidic fragment and the sugar. The selection of a particular peptide structure by the antibody is thus propagated to the carbohydrate through carbohydrate/peptide contacts, which force a change in the orientation of the sugar moiety. This seems to be unfeasible in the α-O-GalNAc-Thr glycopeptide owing to the more limited flexibility of the side chain imposed by the methyl group. Our data demonstrate the non-equivalence of Ser and Thr O-glycosylation points in molecular recognition processes. These features provide insight into the occurrence in nature of the APDTRP epitope for anti-MUC1 antibodies. PMID:26118689

  6. Phagocytosis of breast cancer cells mediated by anti-MUC-1 monoclonal antibody, DF3, and its bispecific antibody.

    PubMed

    Akewanlop, C; Watanabe, M; Singh, B; Walker, M; Kufe, D W; Hayes, D F

    2001-05-15

    Human epithelial mucin, MUC-1, is commonly expressed in adenocarcinoma including 80% of breast cancers. erbB-2 is overexpressed in approximately 30% of breast cancers. Expression of MUC-1 and erbB-2 may be partially overlapping but discoordinate. Therefore, combined use of antibodies directed against these two antigens might increase the number of patients who benefit from immunotherapy. Monoclonal antibody (MAb) DF3 recognizes the MUC-1 tandem repeat. We investigated phagocytosis and cytolysis of cultured human breast cancer cells by monocyte-derived macrophages mediated by MAb DF3 and its bispecific antibody (BsAb) DF3xH22 with the second epitope directed against the Fc component of phagocytic cells. Purified monocytes from healthy donors were cultured with granulocyte macrophage colony-stimulating factor with or without IFN-gamma. antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) assays were performed with these macrophages and MUC-1-expressing target cells (ZR75-1) in the presence of MAb DF3 and BsAb DF3xH22. ADCP was measured by two-color fluorescence flow cytometry using PKH2 (green fluorescent dye) and R-phytoerythrin (RPE) (red)-conjugated MAb against human CD14 and CD11b and was confirmed by confocal microscopy. ADCC was measured by (51)Cr release assay. Immunohistochemical staining studies of MUC-1 and erbB-2 were performed on 67 primary breast cancer tissues. Expression of MUC-1 and erbB-2 was partially overlapping but discoordinate in 67 consecutive breast cancers. Both MAb DF3 and BsAb DF3xH22 mediated ADCP. However, ADCP mediated by MAb DF3 was greater than that mediated by BsAb DF3xH22. ADCC as detected by (51)Cr release was not seen with either antibody. The addition of IFN-gamma to monocyte-derived macrophage cultures inhibited ADCP compared to granulocyte macrophage colony-stimulating factor alone. Given the partially overlapping but discoordinate expression of MUC-1 and erbB-2 in breast cancer

  7. Intratumoral delivery of CpG-conjugated anti-MUC1 antibody enhances NK cell anti-tumor activity

    PubMed Central

    Schettini, Jorge; Kidiyoor, Amritha; Besmer, Dahlia M.; Tinder, Teresa L.; Roy, Lopamudra Das; Lustgarten, Joseph; Gendler, Sandra J.

    2013-01-01

    Monoclonal antibodies (mAbs) against tumor-associated antigens are useful anticancer agents. Antibody-dependent cellular cytotoxicity (ADCC) is one of the major mechanisms responsible for initiating natural killer cell (NK)-mediated killing of tumors. However, the regulation of ADCC via NK cells is poorly understood. We have investigated the cytolytic activity of NK cells against pancreatic cancer cells that were coated with an antibody directed against the human tumor antigen, Mucin-1 designated HMFG-2, either alone or conjugated to CpG oligodeoxynucleotide (CpG ODN). Conjugated antibodies were tested for their ability to elicit ADCC in vitro and in vivo against pancreatic cancer cells. NK cells cultured in the presence of immobilized CpG ODN, HMFG-2 Ab, or CpG ODN-conjugated HMFG-2 Ab were able to up-regulate perforin similarly. Interestingly, a significant higher ADCC was observed when CpG ODN-conjugated HMFG-2-coated tumor cells were co-cultured with NK cells compared to unconjugated HMFG-2 Ab or CpG ODN alone. Moreover, MyD88-deficient NK cells can perform ADCC in vitro. Furthermore, intratumoral injections of CpG ODN-conjugated HMFG-2 induced a significant reduction in tumor burden in vivo in an established model of pancreatic tumor in nude mice compared to CpG ODN or the HMFG-2 alone. Depletion of macrophages or NK cells before treatment confirmed that both cells were required for the anti-tumor response in vivo. Results also suggest that CpG ODN and HMFG-2 Ab could be sensed by NK cells on the mAb-coated tumor cells triggering enhanced ADCC in vitro and in vivo. PMID:22543528

  8. The Human Experience with Intravenous Levodopa

    PubMed Central

    Siddiqi, Shan H.; Abraham, Natalia K.; Geiger, Christopher L.; Karimi, Morvarid; Perlmutter, Joel S.; Black, Kevin J.

    2016-01-01

    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. At least 2760 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: At least 2760 patients have received IV levodopa with a safety profile comparable to that seen with oral administration. PMID:26779024

  9. Metabolism of intravenous methylnaltrexone in mice, rats, dogs, and humans.

    PubMed

    Chandrasekaran, Appavu; Tong, Zeen; Li, Hongshan; Erve, John C L; DeMaio, William; Goljer, Igor; McConnell, Oliver; Rotshteyn, Yakov; Hultin, Theresa; Talaat, Rasmy; Scatina, JoAnn

    2010-04-01

    Methylnaltrexone (MNTX), a selective mu-opioid receptor antagonist, functions as a peripherally acting receptor antagonist in tissues of the gastrointestinal tract. This report describes the metabolic fate of [(3)H]MNTX or [(14)C]MNTX bromide in mice, rats, dogs, and humans after intravenous administration. Separation and identification of plasma and urinary MNTX metabolites was achieved by high-performance liquid chromatography-radioactivity detection and liquid chromatography/mass spectrometry. The structures of the most abundant human metabolites were confirmed by chemical synthesis and NMR spectroscopic analysis. Analysis of radioactivity in plasma and urine showed that MNTX underwent two major pathways of metabolism in humans: sulfation of the phenolic group to MNTX-3-sulfate (M2) and reduction of the carbonyl group to two epimeric alcohols, methyl-6alpha-naltrexol (M4) and methyl-6beta-naltrexol (M5). Neither naltrexone nor its metabolite 6beta-naltrexol were detected in human plasma after administration of MNTX, confirming an earlier observation that N-demethylation was not a metabolic pathway of MNTX in humans. The urinary metabolite profiles in humans were consistent with plasma profiles. In mice, the circulating and urinary metabolites included M5, MNTX-3-glucuronide (M9), 2-hydroxy-3-O-methyl MNTX (M6), and its glucuronide (M10). M2, M5, M6, and M9 were observed in rats. Dogs produced only one metabolite, M9. In conclusion, MNTX was not extensively metabolized in humans. Conversion to methyl-6-naltrexol isomers (M4 and M5) and M2 were the primary pathways of metabolism in humans. MNTX was metabolized to a higher extent in mice than in rats, dogs, and humans. Glucuronidation was a major metabolic pathway in mice, rats, and dogs, but not in humans. Overall, the data suggested species differences in the metabolism of MNTX.

  10. Intravenous immune globulin suppresses angiogenesis in mice and humans

    PubMed Central

    Yasuma, Reo; Cicatiello, Valeria; Mizutani, Takeshi; Tudisco, Laura; Kim, Younghee; Tarallo, Valeria; Bogdanovich, Sasha; Hirano, Yoshio; Kerur, Nagaraj; Li, Shengjian; Yasuma, Tetsuhiro; Fowler, Benjamin J; Wright, Charles B; Apicella, Ivana; Greco, Adelaide; Brunetti, Arturo; Ambati, Balamurali K; Helmers, Sevim Barbasso; Lundberg, Ingrid E; Viklicky, Ondrej; Leusen, Jeanette HW; Verbeek, J Sjef; Gelfand, Bradley D; Bastos-Carvalho, Ana; De Falco, Sandro; Ambati, Jayakrishna

    2016-01-01

    Human intravenous immune globulin (IVIg), a purified IgG fraction composed of ~ 60% IgG1 and obtained from the pooled plasma of thousands of donors, is clinically used for a wide range of diseases. The biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG (IgG) Fc regions. Recently, we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI, a high-affinity receptor for IgG1. Here we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases, namely, neovascular age-related macular degeneration, corneal neovascularization, colorectal cancer, fibrosarcoma and peripheral arterial ischemic disease. Angioinhibition was mediated by the Fc region of IVIg, required FcγRI and had similar potency in transgenic mice expressing human FcγRs. Finally, IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel densities. These data place IVIg, an agent approved by the US Food and Drug Administration, as a novel angioinhibitory drug in doses that are currently administered in the clinical setting. In addition, they raise the possibility of an unintended effect of IVIg on blood vessels. PMID:26925256

  11. Intraocular Penetration of Intravenous Micafungin in Inflamed Human Eyes

    PubMed Central

    Sawada, Akira; Suemori, Shinsuke; Kawakami, Hideaki; Niwa, Yoshiaki; Kondo, Yuji; Ohkusu, Kiyofumi; Yamada, Noriaki; Ogura, Shinji; Yaguchi, Takashi; Nishimura, Kazuko; Kishino, Satoshi

    2013-01-01

    Eight eyes of 7 patients with fungal disease received intravenous injections of 150 to 300 mg micafungin, and samples of blood, cornea, retina-choroid, aqueous humor, and vitreous humor were collected. The micafungin levels in all collected samples exceeded the MICs; however, the levels in the vitreous and aqueous humors were lower. Our findings suggest that intravenous micafungin should be given in combination with intravitreal antifungal agents after vitrectomy in severe cases of intraocular fungal diseases. PMID:23689706

  12. Changes of human plasma dopamine-beta-hydroxylase activity after intravenous administration of theophylline.

    PubMed

    Aunis, D; Mandel, P; Miras-Portugal, M T; Coquillat, G; Rohmer, F; Warter, J M

    1975-03-01

    The intravenous administration of theophylline to ten healthy human subjects produced either an increase of circulating plasma dopamine-beta-hydroxylase or no change. The rise of plasma enzyme activity may reflect the increased peripheral catecholamine release induced by theophylline.

  13. Pharmacokinetics of high-dose intravenous melatonin in humans.

    PubMed

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette M; Fenger, Andreas Q; Petersen, Marian C; Rosenberg, Jacob; Gögenur, Ismail

    2016-03-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221,500.0 (185,637.5-326,175.0) pg/mL and 1,251,500.0 (864,375.0-1,770,500.0) pg/mL, respectively; mean (SD) t1/2 was 42.3 (5.6) minutes and 46.2 (6.2) minutes; mean (SD) Vd was 1.6 (0.9) L/kg and 2.0 (0.8) L/kg; mean (SD) CL was 0.0253 (0.0096) L/min · kg and 0.0300 (0.0120) L/min · kg; and median (IQR) AUC0- ∞ , 8,997,633.0 (6,071,696.2-11,602,811.9) pg · min/mL and 54,685,979.4 (36,028,638.6-105,779,612.0) pg · min/mL. High-dose intravenous melatonin did not induce sedation, evaluated as simple reaction times. No adverse effects were reported in the study.

  14. Neutralizing activities against seasonal influenza viruses in human intravenous immunoglobulin

    PubMed Central

    Onodera, Hiroyuki; Urayama, Takeru; Hirota, Kazue; Maeda, Kazuhiro; Kubota-Koketsu, Ritsuko; Takahashi, Kazuo; Hagiwara, Katsuro; Okuno, Yoshinobu; Ikuta, Kazuyoshi; Yunoki, Mikihiro

    2017-01-01

    Influenza viruses A/H1N1, A/H3N2, and B are known seasonal viruses that undergo annual mutation. Intravenous immunoglobulin (IVIG) contains anti-seasonal influenza virus globulins. Although the virus-neutralizing (VN) titer is an indicator of protective antibodies, changes in this titer over extended time periods have yet to be examined. In this study, variations in hemagglutination inhibition (HI) and VN titers against seasonal influenza viruses in IVIG lots over extended time periods were examined. In addition, the importance of monitoring the reactivity of IVIG against seasonal influenza viruses with varying antigenicity was evaluated. A/H1N1, A/H3N2, and B influenza virus strains and IVIG lots manufactured from 1999 to 2014 were examined. The HI titer was measured by standard methods. The VN titer was measured using a micro-focus method. IVIG exhibited significant HI and VN titers against all investigated strains. Our results suggest that the donor population maintains both specific and cross-reactive antibodies against seasonal influenza viruses, except in cases of pandemic viruses, despite major antigen changes. The titers against seasonal influenza vaccine strains, including past strains, were stable over short time periods but increased slowly over time. PMID:28331286

  15. Changes of human plasma dopamine-beta-hydroxylase activity after intravenous administration of theophylline.

    PubMed Central

    Aunis, D; Mandel, P; Miras-Portugal, M T; Coquillat, G; Rohmer, F; Warter, J M

    1975-01-01

    The intravenous administration of theophylline to ten healthy human subjects produced either an increase of circulating plasma dopamine-beta-hydroxylase or no change. The rise of plasma enzyme activity may reflect the increased peripheral catecholamine release induced by theophylline. PMID:1137731

  16. Rapid intravenous administration of amino acids prevents biliary sludge induced by total parenteral nutrition in humans.

    PubMed

    Wu, Z S; Yu, L; Lin, Y J; Jun, Z J; Min, W S; Jun, Y; Hua, Z B

    2000-01-01

    The aim of this study was to evaluate whether daily rapid intravenous administration of amino acids (IVAA) prevented the formation of biliary sludge in humans receiving long-term total parenteral nutrition (TPN). Thirty adult patients receiving TPN for more than 28 consecutive days were studied. They were randomized to receive either saline solution (placebo) intravenously (15 patients) or 6.9% branched chain amino acid (BCAA)-enriched amino acid (15 synthetic amino acids; Freamine HBC) solution given by administration rapid intravenous (15 patients). The groups were similar with respect to age, sex, diagnosis, liver function test results, amylase levels, TPN time, and time of study. All patients underwent weekly ultrasound studies. Volume and emptying studies of the gallbladder in response to the study drug were performed after 1 week. As a result, none of the patients receiving rapid IVAA had sludge, whereas 11 of the 15 patients receiving placebo had sludge (P < 0.01). Results of emptying studies showed significant contraction of the gallbladder in those in the rapid IVAA group, but not in the placebo group. Consequently, the data suggest that rapid IVAA given daily prevents TPN-induced stasis and sludge in the gallbladder. We conclude that rapid IVAA should be used as routine prophylaxis against biliary sludge and formation of gallstones in patients receiving long-term TPN.

  17. Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

    PubMed Central

    Terpstra, Melissa; Torkelson, Carolyn; Emir, Uzay; Hodges, James S.; Raatz, Susan

    2011-01-01

    Until now, the lack of a means to detect a deficiency or to measure the pharmacologic effect in the human brain in situ has been a hindrance to the development of antioxidant-based prevention and treatment of dementia. In this study, a recently developed 1H MRS approach was applied to quantify key human brain antioxidant concentrations throughout the course of an aggressive antioxidant-based intervention. The concentrations of the two most abundant central nervous system chemical antioxidants, vitamin C and glutathione, were quantified noninvasively in the human occipital cortex prior to and throughout 24 h after bolus intravenous delivery of 3 g of vitamin C. Although the kinetics of the sodium-dependent vitamin C transporter and physiologic blood vitamin C concentrations predict theoretically that brain vitamin C concentration will not increase above its homeostatically maintained level, this theory has never been tested experimentally in the living human brain. Therefore, human brain vitamin C and glutathione concentrations were quantified noninvasively using MEGA-PRESS double-edited 1H MRS and LCModel. Healthy subjects (age, 19–63 years) with typical dietary consumption, who did not take vitamin supplements, fasted overnight and then reported for the measurement of baseline antioxidant concentrations. They then began controlled feeding which they adhered to until after vitamin C and glutathione concentrations had been measured at 2, 6, 10 and 24 h after receiving intravenous vitamin C. Two of the twelve studies were sham controls in which no vitamin C was administered. The main finding was that human brain vitamin C and glutathione concentrations remained constant throughout the protocol, even though blood serum vitamin C concentrations spanned from the low end of the normal range to very high. PMID:21674654

  18. Behavioral risk factors and human immunodeficiency virus (HIV) prevalence among intravenous drug users in Puerto Rico.

    PubMed

    Robles, R R; Colón, H M; Sahai, H; Matos, T D; Marrero, C A; Reyes, J C

    1992-03-01

    This study reports on four empirical models likely to contribute to understanding the behaviors linked with human immunodeficiency virus (HIV) among intravenous drug users. The sample comprises 1,637 intravenous drug users recruited between May 1989 and June 1990 in San Juan, Puerto Rico. Adjusting for sociodemographics, four logistic regression models were constructed to assess the association of risk behaviors with HIV seropositivity. In model 1, the variables found to be significantly associated with HIV seropositivity were injecting four times a day, injection as the only route of consuming drugs, and years of injection. In model 2, the only risk behavior significantly associated with HIV seropositivity was injecting drugs in shooting galleries. In model 3, all sex risk variables failed to meet the adjusted level of significance. In model 4, pneumonia, hepatitis, and syphilis were significantly linked with HIV infection. In order to assess the individual effects of the significant variables in each one of the four models, a logistic regression analysis was performed simultaneously controlling for all of the variables. After adjustment for the Bonferroni correction, age group 25-34 years, injection as the only route of using drugs, number of years of injection, and syphilis were the only significant variables remaining.

  19. Intravenous lipid emulsion as antidote: a summary of published human experience.

    PubMed

    Cave, Grant; Harvey, Martyn; Graudins, Andis

    2011-04-01

    Intravenous lipid emulsion (ILE) has been demonstrated to be effective in amelioration of cardiovascular and central nervous system sequelae of local-anaesthetic and non-local-anaesthetic drug toxicity in animal models. Sequestration of lipophilic toxins to an expanded plasma lipid phase is credited as the predominant beneficial mechanism of action of ILE. Systematic review of published human experience is however lacking. We determined to report a comprehensive literature search of all human reports of ILE application in drug poisoning. Forty-two cases of ILE use (19 local-anaesthetic, 23 non-local-anaesthetic) were identified, with anecdotal reports of successful resuscitation from cardiovascular collapse and central nervous system depression associated with ILE administration in lipophilic toxin overdose. Although significant heterogeneity was observed in both agents of intoxication, and reported outcomes; case report data suggest a possible benefit of ILE in potentially life-threatening cardio-toxicity from bupivacaine, mepivacaine, ropivacaine, haloperidol, tricyclic antidepressants, lipophilic beta blockers and calcium channel blockers. Further controlled study and systematic evaluation of human cases is required to define the clinical role of ILE in acute poisonings.

  20. Multiple Intravenous Administrations of Human Umbilical Cord Blood Cells Benefit in a Mouse Model of ALS

    PubMed Central

    Garbuzova-Davis, Svitlana; Rodrigues, Maria C. O.; Mirtyl, Santhia; Turner, Shanna; Mitha, Shazia; Sodhi, Jasmine; Suthakaran, Subatha; Eve, David J.; Sanberg, Cyndy D.; Kuzmin-Nichols, Nicole; Sanberg, Paul R.

    2012-01-01

    Background A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25×106 cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages. Methodology/Principal Findings Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 106 or 2.5×106 cells from 13 weeks of age. A third, pre-symptomatic, group received 106 cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 106 cells pre-symptomatically or 2.5×106 cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups. Conclusions/Significance These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies. PMID:22319620

  1. Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration

    PubMed Central

    van der Valk, Fleur M.; van Wijk, Diederik F.; Lobatto, Mark E.; Verberne, Hein J.; Storm, Gert; Willems, Martine C.M.; Legemate, Dink A.; Nederveen, Aart J.; Calcagno, Claudia; Mani, Venkatesh; Ramachandran, Sarayu; Paridaans, Maarten P.M.; Otten, Maarten J.; Dallinga-Thie, Geesje M.; Fayad, Zahi A.; Nieuwdorp, Max; Schulte, Dominik M.; Metselaar, Josbert M.; Mulder, Willem J.M.; Stroes, Erik S.

    2015-01-01

    Drug delivery to atherosclerotic plaques via liposomal nanoparticles may improve therapeutic agents’ risk–benefit ratios. Our paper details the first clinical studies of a liposomal nanoparticle encapsulating prednisolone (LN-PLP) in atherosclerosis. First, PLP’s liposomal encapsulation improved its pharmacokinetic profile in humans (n = 13) as attested by an increased plasma half-life of 63 h (LN-PLP 1.5 mg/kg). Second, intravenously infused LN-PLP appeared in 75% of the macrophages isolated from iliofemoral plaques of patients (n = 14) referred for vascular surgery in a randomized, placebo-controlled trial. LN-PLP treatment did however not reduce arterial wall permeability or inflammation in patients with atherosclerotic disease (n = 30), as assessed by multimodal imaging in a subsequent randomized, placebo-controlled study. In conclusion, we successfully delivered a long-circulating nanoparticle to atherosclerotic plaque macrophages in patients, whereas prednisolone accumulation in atherosclerotic lesions had no anti-inflammatory effect. Nonetheless, the present study provides guidance for development and imaging-assisted evaluation of future nanomedicine in atherosclerosis. PMID:25791806

  2. A baboon syndrome induced by intravenous human immunoglobulins: report of a case and immunological analysis.

    PubMed

    Barbaud, A; Tréchot, P; Granel, F; Lonchamp, P; Faure, G; Schmutz, J L; Béné, M C

    1999-01-01

    Following the second series of intravenous human immunoglobulins (IVIg; 0.4 g/kg) prescribed to treat a sensorimotor polyneuritis, a 28-year-old woman developed pompholyx that recurred after each of the following monthly treatments with IVIg. During the administration of the 10th series, the patient developed a typical baboon syndrome. Immunohistochemical studies of a skin biopsy revealed an unexpected epidermal expression of P-selectin, usually expressed by endothelial cells. Patch, prick and intradermal tests performed with IVIg on the back, arms and buttocks gave negative results on immediate and delayed readings. IVIg were re-administered, with the informed consent of the patient, and induced a generalized maculopapular rash. This is the first reported case of baboon syndrome induced by IVIg. Although extensive skin testing was performed, all test sites remained negative. We wonder whether IVIg could reproduce immunological mechanisms involved in the 3 types of systemic contact dermatitis (pompholyx, baboon syndrome and maculopapular rash), including the epidermal expression of P-selectin.

  3. Intravenous immunoglobulin products contain specific antibodies to recombinant human tau protein.

    PubMed

    Smith, Lynnae M; Coffey, Mary P; Klaver, Andrea C; Loeffler, David A

    2013-08-01

    Intravenous immunoglobulin (IVIG) products are prepared from plasma immunoglobulins from healthy donors. Pilot studies suggest that IVIG may stabilize cognitive functioning in patients with mild-to-moderate Alzheimer's disease. This study measured antibodies to recombinant human tau protein in the IVIG products Gammagard (Baxter), Gamunex (Talecris), and Flebogamma (Grifols). Anti-tau antibodies were measured by ELISA, subtracting IVIG's polyvalent binding from its binding to tau-coated wells to calculate specific anti-tau antibody levels. Because polyvalent binding of IVIG products may interfere with ELISA measurement of their specific antibody levels, the percentage of binding of each IVIG product to tau-coated wells that was specific for tau was also determined. Specific anti-tau antibodies were detected in all three IVIG products, with significant differences between these products (p<0.001) even when Flebogamma's anti-tau antibodies were doubled to account for its preparation as a 5% solution vs. 10% solutions for Gammagard and Gamunex (means: Gammagard, 3.1 μg/ml; Gamunex, 2.5 μg/ml; Flebogamma, 1.2 μg/ml). The percentages of each IVIG product's specific binding to tau-coated wells also varied between the various products (p<0.001) and between all pairs of IVIG products (means: Gammagard, 73.1%; Flebogamma, 54.5%; Gamunex, 37.4%; p<0.01 for all pairwise comparisons). These findings indicate that IVIG products contain specific anti-tau antibodies. The concentrations of these antibodies and the percentages of specific binding of IVIG to tau-coated wells vary between IVIG products. Further studies are indicated to determine if IVIG also contains antibodies to pathologic forms of tau.

  4. Successful clearance of human parainfluenza virus type 2 viraemia with intravenous ribavirin and immunoglobulin in a patient with acute myocarditis.

    PubMed

    Kalimuddin, Shirin; Sessions, October M; Hou, Yan'An; Ooi, Eng Eong; Sim, David; Cumaraswamy, Sivathasan; Tan, Teing Ee; Lai, Siang Hui; Low, Chian Yong

    2013-01-01

    Human parainfluenza virus (HPIV) infection as an aetiology of acute viral myocarditis is rare, with only few cases reported in the literature to date. Here we report a case of fulminant HPIV-2 myocarditis in a 47 year-old man with viraemia who was successfully treated with intravenous ribavirin and intravenous immunoglobulin (IVIG). There are currently no recommendations on the treatment of HPIV myocarditis. We are, to our knowledge, the first to report a patient with a documented HPIV-2 viraemia that subsequently cleared after the initiation of antiviral therapy. Although it is difficult to definitively attribute the patient's clinical improvement to ribavirin or IVIG alone, our case does suggest that clinicians may wish to consider initiating ribavirin and IVIG in patients with HPIV myocarditis and persistent viraemia not responding to supportive measures alone.

  5. Absence of pharmacokinetic interaction between intravenous peramivir and oral oseltamivir or rimantadine in humans.

    PubMed

    Atiee, George; Lasseter, Kenneth; Baughman, Sharon; McCullough, Amy; Collis, Phil; Hollister, Alan; Hernandez, Jaime

    2012-09-01

    Peramivir, an intravenously administered neuraminidase inhibitor, may be used concomitantly with other influenza antivirals. Two studies were conducted to assess the potential for pharmacokinetic interactions of peramivir when coadministered with oseltamivir or rimantadine. Twenty-one healthy subjects were enrolled in each randomized, open-label, crossover study, and they received 1 intravenous dose of peramivir (600 mg), 1 oral dose of oseltamivir (75 mg) or rimantadine (100 mg), or a combination of peramivir with oseltamivir or rimantadine. Assessment of the 90% confidence interval for the geometric mean ratio of peramivir and oseltamivir carboxylate or rimantadine pharmacokinetic parameters showed no effect of oseltamivir or rimantadine on the pharmacokinetics of peramivir and no effect of peramivir on the pharmacokinetics of oseltamivir carboxylate or rimantadine. The drugs were well tolerated. These results suggest no reason to expect an effect of concomitant administration of oseltamivir or rimantadine on the safety profile of peramivir in patients with influenza.

  6. Intravenous Therapy.

    ERIC Educational Resources Information Center

    Galliart, Barbara

    Intended for teaching licensed practical nurses, this curriculum guide provides information related to the equipment and skills required for nursing care of patients needing intravenous (IV) therapy. It also explains the roles and responsibilities of the licensed practical nurse with regard to intravenous therapy. Each of the 15 instructional…

  7. Intravenously injected Newcastle disease virus in non-human primates is safe to use for oncolytic virotherapy.

    PubMed

    Buijs, P R A; van Amerongen, G; van Nieuwkoop, S; Bestebroer, T M; van Run, P R W A; Kuiken, T; Fouchier, R A M; van Eijck, C H J; van den Hoogen, B G

    2014-11-01

    Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic potential. Detailed preclinical information regarding the safety of oncolytic NDV is scarce. In this study, we evaluated the toxicity, biodistribution and shedding of intravenously injected oncolytic NDVs in non-human primates (Macaca fascicularis). Two animals were injected with escalating doses of a non-recombinant vaccine strain, a recombinant lentogenic strain or a recombinant mesogenic strain. To study transmission, naive animals were co-housed with the injected animals. Injection with NDV did not lead to severe illness in the animals or abnormalities in hematologic or biochemistry measurements. Injected animals shed low amounts of virus, but this did not lead to seroconversion of the contact animals. Postmortem evaluation demonstrated no pathological changes or evidence of virus replication. This study demonstrates that NDV generated in embryonated chicken eggs is safe for intravenous administration to non-human primates. In addition, our study confirmed results from a previous report that naïve primate and human sera are able to neutralize egg-generated NDV. We discuss the implications of these results for our study and the use of NDV for virotherapy.

  8. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans

    PubMed Central

    Manini, Alex F.; Yiannoulos, Georgia; Bergamaschi, Mateus M.; Hernandez, Stephanie; Olmedo, Ruben; Barnes, Allan J.; Winkel, Gary; Sinha, Rajita; Jutras-Aswad, Didier; Huestis, Marilyn A.; Hurd, Yasmin L.

    2015-01-01

    Objectives Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods This double-blind, placebo-controlled cross-over study of CBD co-administered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21–65 years with prior opioid exposure, regardless of route. Blood samples were obtained before and after 400 or 800 mg CBD pretreatment, followed by a single 0.5 (Session 1) or 1.0mcg/Kg (Session 2) intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. Following low dose CBD, tmax occurred at 3 and 1.5h (Sessions 1 and 2, respectively). Following high dose CBD, tmax occurred at 3 and 4h in Sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC p=NS) between sessions. Conclusions CBD does not exacerbate adverse effects associated with intravenous fentanyl administration. Co-administration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse. PMID:25748562

  9. Intravenously Injected Human Apolipoprotein A‐I Rapidly Enters the Central Nervous System via the Choroid Plexus

    PubMed Central

    Stukas, Sophie; Robert, Jerome; Lee, Michael; Kulic, Iva; Carr, Michael; Tourigny, Katherine; Fan, Jianjia; Namjoshi, Dhananjay; Lemke, Kalistyne; DeValle, Nicole; Chan, Jeniffer; Wilson, Tammy; Wilkinson, Anna; Chapanian, Rafi; Kizhakkedathu, Jayachandran N.; Cirrito, John R.; Oda, Michael N.; Wellington, Cheryl L.

    2014-01-01

    Background Brain lipoprotein metabolism is dependent on lipoprotein particles that resemble plasma high‐density lipoproteins but that contain apolipoprotein (apo) E rather than apoA‐I as their primary protein component. Astrocytes and microglia secrete apoE but not apoA‐I; however, apoA‐I is detectable in both cerebrospinal fluid and brain tissue lysates. The route by which plasma apoA‐I enters the central nervous system is unknown. Methods and Results Steady‐state levels of murine apoA‐I in cerebrospinal fluid and interstitial fluid are 0.664 and 0.120 μg/mL, respectively, whereas brain tissue apoA‐I is ≈10% to 15% of its levels in liver. Recombinant, fluorescently tagged human apoA‐I injected intravenously into mice localizes to the choroid plexus within 30 minutes and accumulates in a saturable, dose‐dependent manner in the brain. Recombinant, fluorescently tagged human apoA‐I accumulates in the brain for 2 hours, after which it is eliminated with a half‐life of 10.3 hours. In vitro, human apoA‐I is specifically bound, internalized, and transported across confluent monolayers of primary human choroid plexus epithelial cells and brain microvascular endothelial cells. Conclusions Following intravenous injection, recombinant human apoA‐I rapidly localizes predominantly to the choroid plexus. Because apoA‐I mRNA is undetectable in murine brain, our results suggest that plasma apoA‐I, which is secreted from the liver and intestine, gains access to the central nervous system primarily by crossing the blood–cerebrospinal fluid barrier via specific cellular mediated transport, although transport across the blood–brain barrier may also contribute to a lesser extent. PMID:25392541

  10. Pupil responses to intravenous heroin (diamorphine) in dependent and non-dependent humans.

    PubMed

    Tress, K H; El-Sobky, A A

    1979-02-01

    1. Intravenous heroin was administered to volunteers, in doses of 2.5 and 5 mg to non-dependent subjects and does of 1/6, 1/3 and 1/2 of their prescribed daily does of opiates to dependent subjects, and pupillary responses measured before and three times during the 2 h after injection. 2. Tolerance to the miotic effects of heroin in the dependent subjects was demonstrated--larger doses of heroin were needed to produce the same pupil response in dependent subjects than in non-dependent subjects and the duration of action was shorter in the former group. 3. The effect of concurrent oral methadone medication on pupil response to heroin was demonstrated. Subjects prescribed both methadone and heroin showed smaller control pupil diameters and a reduced dose effect to heroin than did subjects prescribed heroin alone.

  11. Human pharmacokinetics and toxicity of high-dose metronidazole administered orally and intravenously

    SciTech Connect

    Urtasun, R.C.; Rabin, H.R.; Partington, J.

    1983-01-01

    This study is part of a clinical program to assess the use of nitroimidazoles as radiosensitizers of hypoxic tumor cells. A total of 37 patients with malignant tumors have been entered into the study to receive oral high-dose metronidazole in conjunction with radiation. Twenty-eight patients with malignant brain tumors received 6 gm/m2 three times a week for 3 weeks (a mean total dose of 5.3 gm/m2). Maximum mean plasma drug concentration of 1 mM was obtained at 4 hours after drug ingestion with a mean half-life of 13 hours. Tissue and cerebrospinal fluid levels of 80% to 90% of the plasma levels were obtained at 4 to 6 hours. A linear relationship between increased drug dose and increased plasma concentration was observed at doses of 2.5 gm/m2 up to 6 gm/m2. Acute gastrointestinal and central nervous system toxicity was the dose-limiting factor (50% and 25%, respectively, at total doses of 5.3 gm/m2). Pharmacokinetic studies of intravenous metronidazole were performed in eight consenting patients. Single doses of 0.5, 1, 1.5, and 2 gm were administered intravenously by zero-order infusion pump. Seven of the eight patients received a second identical dose orally 1 week later and the results were compared. Open two-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion rate equations, by use of a nonlinear least-squares regression analysis program (NONLIN). The mean (+/- SD) for alpha half-life was 1.2 +/- 1.3 hours, and that for the beta half-life was 9.8 +/- 5.9 hours. The absolute oral bioavailability was estimated to approximate 100%.

  12. Different population dynamics of human T cell lymphotropic virus type II in intravenous drug users compared with endemically infected tribes

    PubMed Central

    Salemi, Marco; Lewis, Martha; Egan, John Fergal; Hall, William W.; Desmyter, Jan; Vandamme, Anne-Mieke

    1999-01-01

    The phylogeny of human T cell lymphotropic virus type II (HTLV-II) was investigated by using strains isolated from Amerindian and Pygmy tribes, in which the virus is maintained primarily through mother-to-child transmission via breast-feeding, and strains from intravenous drug users (IDUs), in which spread is mainly blood-borne via needle sharing. Molecular clock analysis showed that HTLV-II has two different evolutionary rates with the molecular clock for the virus in IDUs ticking 150–350 times faster than the one in endemically infected tribes: 2.7 × 10−4 compared with 1.71/7.31 × 10−7 nucleotide substitutions per site per year in the long terminal repeat region. This dramatic acceleration of the evolutionary rate seems to be related with the mode of transmission. Mathematical models showed the correlation of these two molecular clocks with an endemic spread of HTLV-II in infected tribes compared with the epidemic spread in IDUs. We also noted a sharp increase in the population size of the virus among IDUs during the last decades probably caused by the worldwide increase in intravenous drug use. PMID:10557307

  13. Development and pharmacokinetic characterization of pulmonal and intravenous delta-9-tetrahydrocannabinol (THC) in humans.

    PubMed

    Naef, Myrtha; Russmann, Stefan; Petersen-Felix, Steen; Brenneisen, Rudolf

    2004-05-01

    The aim of the present study was to develop a physiologically compatible inhalation solution of delta-9-tetrahydrocannabinol (THC), and to compare the pharmacokinetic and analgesic properties of pulmonal THC versus pulmonal placebo and intravenous (iv) THC, respectively. Eight healthy volunteers were included in this randomized, double-blind, crossover study. The aqueous THC formulations were prepared by using a solubilization technique. iv THC (0.053 mg/kg body weight), pulmonal THC (0.053 mg/kg), or a placebo inhalation solution was administered as single dose. At defined time points, blood samples were collected, and somatic and psychotropic side effects as well as vital functions monitored. An ice water immersion test was performed to measure analgesia. Using a pressure-driven nebulizer, the pulmonal administration of the THC liquid aerosol resulted in high THC peak plasma levels within minutes. The bioavailability of the pulmonal THC was 28.7 +/- 8.2% (mean +/- SEM). The side effects observed after pulmonal THC were coughing and slight irritation of the upper respiratory tract, very mild psychotropic symptoms, and headache. The side effects after iv THC were much more prominent. Neither pulmonal nor iv THC significantly reduced experimentally induced pain.

  14. Pharmacokinetics of cefpimizole in normal humans after single- and multiple-dose intravenous infusions.

    PubMed Central

    Lakings, D B; Friis, J M; Brown, R J; Allen, H R

    1984-01-01

    The pharmacokinetics of cefpimizole (free acid equivalents of cefpimizole sodium), a broad-spectrum cephalosporin antibiotic, were determined after single- and multiple-dose 20-min intravenous infusions of 1, 2, and 4 g. The kinetics of single-dose administration of cefpimizole correspond to a two-compartment model with an average apparent volume of distribution of 20.0 +/- 3.5 liters, a distribution rate constant of 2.24 +/- 1.00 h-1, and a terminal rate constant of 0.358 +/- 0.036 h-1 (half-life, 1.9 h). The total body clearance was 118.6 +/- 20.2 ml/min. The primary route of elimination for cefpimizole was the renal route, with approximately 80% of the administered dose excreted as the parent compound. The elimination rate constant, as calculated from urinary excretion data, was 0.339 +/- 0.043 h-1, which is in close agreement with the terminal rate constant for plasma. Renal clearance of cefpimizole was 96.2 +/- 17.3 ml/min. Dose proportionality over the three dose levels was obtained from area under the plasma curve and cumulative urinary excretion data. The results of the multiple-dose study indicated that no apparent change in the distribution or elimination kinetics of cefpimizole occurred after the administration of 1-, 2-, and 4-g doses for 7 days, three times a day. The kinetics from the multiple-dose study were in close agreement with those from the single-dose study. No accumulation of cefpimizole occurred, and nondetectable levels was observed 24 h after administration of the last dose. Peaks that could be attributed to metabolites of cefpimizole were not observed during high-pressure liquid chromatographic analysis of either plasma or urine specimens. PMID:6524897

  15. Diet induced thermogenesis with oral & intravenous feeding in chronically undernourished human subjects.

    PubMed

    Sekhar, R V; Shetty, P S; Kurpad, A V

    1998-12-01

    The parasympathetic nervous system (PNS) has been shown to be important in the mediation of diet induced thermogenesis (DIT). Chronically energy deficient (CED) subjects have a high resting parasympathetic tone, which could lead to a greater than expected DIT. DIT was studied in chronically energy deficient adult men and healthy age-matched volunteers (6 controls, 7 CED subjects) with an isocaloric (600 kcal) meal given by the oral and intravenous (i.v.) routes on two consecutive days, on a crossover basis. The resting metabolic rate (RMR) and the DIT were measured over 6 h, along with cardiovascular, biochemical and anthropometric parameters. Anthropometrically (height, weight, fat free mass, body mass index, mid upper arm circumference and sum of skinfolds), the CED group differed significantly from the well-nourished control group. There were no significant differences between the two groups in the basal state for metabolic (RMR, oxygen consumption, respiratory quotient), cardiovascular [blood pressure (BP), heart rate, cardiac output], and biochemical (plasma glucose, insulin and norepinephrine) parameters. The CED group had a significantly higher DIT response for both meal types when compared to the controls, when expressed as an absolute value and as a percentage response. However, the response was not significant when corrected for the meal size and body weight. There were also no significant differences between the two meal types in each group for the metabolic, cardiovascular and biochemical parameters during the DIT period, although, in general, the oral meal gave a larger DIT response compared to the i.v. meal. Both groups predominantly oxidised fat during the fasted stage and switched to carbohydrate oxidation when fed. It appears that, the previously demonstrated higher tone in the PNS, does not make a significant contribution to the thermic response of a meal in these subjects.

  16. Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Until now, antioxidant based initiatives for preventing dementia have lacked a means to detect deficiency or measure pharmacologic effect in the human brain in situ. Objective: Our objective was to apply a novel method to measure key human brain antioxidant concentrations throughout the ...

  17. Intravenous Lipid Emulsion as an Antidote for the Treatment of Acute Poisoning: A Bibliometric Analysis of Human and Animal Studies.

    PubMed

    Zyoud, Sa'ed H; Waring, W Stephen; Al-Jabi, Samah W; Sweileh, Waleed M; Rahhal, Belal; Awang, Rahmat

    2016-11-01

    In recent years, there has been increasing interest in the role of intravenous lipid formulations as potential antidotes in patients with severe cardiotoxicity caused by drug toxicity. The aim of this study was to conduct a comprehensive bibliometric analysis of all human and animal studies featuring lipid emulsion as an antidote for the treatment of acute poisoning. The Scopus database search was performed on 5 February 2016 to analyse the research output related to intravenous lipid emulsion as an antidote for the treatment of acute poisoning. Research indicators used for analysis included total number of articles, date (year) of publication, total citations, value of the h-index, document types, countries of publication, journal names, collaboration patterns and institutions. A total of 594 articles were retrieved from Scopus database for the period of 1955-2015. The percentage share of global intravenous lipid emulsion research output showed that research output was 85.86% in 2006-2015 with yearly average growth in this field of 51 articles per year. The USA, United Kingdom (UK), France, Canada, New Zealand, Germany, Australia, China, Turkey and Japan accounted for 449 (75.6%) of all the publications. The total number of citations for all documents was 9,333, with an average of 15.7 citations per document. The h-index of the retrieved documents for lipid emulsion research as antidote for the treatment of acute poisoning was 49. The USA and the UK achieved the highest h-indices, 34 and 14, respectively. New Zealand produced the greatest number of documents with international collaboration (51.9%) followed by Australia (50%) and Canada (41.4%) out of the total number of publications for each country. In summary, we found an increase in the number of publications in the field of lipid emulsion after 2006. The results of this study demonstrate that the majority of publications in the field of lipid emulsion were published by high-income countries. Researchers from

  18. Thirteen-week Intravenous Toxicity Study of a Novel Humanized Anti-Human Death Receptor 5 Monoclonal Antibody, CS-1008, in Cynomolgus Monkeys

    PubMed Central

    Tanaka, Kohji; Sugiura, Tomomi; Koyama, Kumiko; Nakamura, Takahiro; Kamimura, Yasuhiro; Takasaki, Wataru; Manabe, Sunao

    2010-01-01

    CS-1008, a humanized monoclonal antibody that is agonistic to human death receptor 5, was intravenously administered to cynomolgus monkeys twice a week for 13 weeks at 3 different dose levels (5, 15 and 42 mg/kg) in order to evaluate its potential toxicity. A control group received phosphate buffered saline containing 0.01% polysorbate 80. Each of the 4 groups consisted of 3 male and 3 female cynomolgus monkeys. No animal in any group died during the dosing period. No toxic changes in clinical signs, food consumption, body weight, electrocardiography, ophthalmology, urinalysis, hematology, blood chemistry, gross pathology, organ weights or histopathology were noted in any group during the dosing period. In the toxicokinetic analysis, the values for the maximum concentration of CS-1008 in plasma and the area under the curve generally increased with increasing dose. No clear differences in the toxicokinetic parameters or profiles were observed between the sexes. Development of anti-CS-1008 antibodies was not detected in any sample. The no-observed adverse-effect level (NOAEL) of CS-1008 in cynomolgus monkeys under the conditions of this study was concluded to be 42 mg/kg in both sexes, when administered intravenously twice a week for 13 weeks. This study supports the development of CS-1008 as a therapeutic biopharmaceutical. PMID:22272006

  19. Human immunodeficiency virus type 1 in illicit-drug solutions used intravenously retains infectivity.

    PubMed

    Bobkov, Aleksei F; Selimova, Ludmila M; Khanina, Tatyana A; Zverev, Sergey Y; Pokrovsky, Vadim V; Weber, Jonathan N; Bobkov, Eugene N; Rylkov, Andrey V

    2005-04-01

    The stability of the human immunodeficiency virus type 1 (HIV-1) strain IIIB in drug solutions was studied. The data demonstrate that HIV-1 infectivity can be retained in drug solutions (e.g. , heroin, "Khanka," and "Vint") for long periods of time. This fact must be taken into account when designing health education programs for the prevention of HIV and AIDS in Eastern Europe.

  20. Parenteral and sexual transmission of human immunodeficiency virus in intravenous drug users: a study of seroconversion. The Northern Italian Seronegative Drug Addicts (NISDA) Study.

    PubMed

    Nicolosi, A; Leite, M L; Musicco, M; Molinari, S; Lazzarin, A

    1992-02-01

    To evaluate the role of parenteral and sexual transmission of human immunodeficiency virus, we studied seronegative intravenous drug users recruited from 25 drug dependence treatment centers in northern Italy. All attending intravenous drug users were asked for their consent and screened for antibodies to human immunodeficiency virus; those who were seronegative were enrolled, interviewed about their habits, and invited to follow-up visits. Between 1987 and 1989, 1,195 seronegative intravenous drug users were enrolled, 635 were followed up (mean duration, 11.9 months), and 35 seroconversions were observed. The incidence rate ratios were 3.3 (95% confidence interval (CI) 1.4-7.5) for subjects aged less than 20 years, 2.4 (95% CI 1.2-4.7) for less than 2 years of intravenous drug use, 2.2 (95% CI 0.9-5.5) for syringe sharing, and 1.0 for subjects with a sexual partner who had tested positive for human immunodeficiency virus. A case-control approach, using logistic regression and adjusting for sex, age, area, and prevalence, showed odds ratios of 13.2 (95% CI 3.1-56.8) for frequent syringe sharing and 4.0 (95% CI 1.5-10.4) for sexual contacts with seropositive partners; frequent use of condoms was associated with a reduction in risk that did not reach statistical significance. Parenteral transmission is the most important route of infection with the human immunodeficiency virus among intravenous drug users, and sexual transmission plays a relevant, additive role.

  1. Intravenous Formulation of HET0016 Decreased Human Glioblastoma Growth and Implicated Survival Benefit in Rat Xenograft Models.

    PubMed

    Jain, Meenu; Gamage, Nipuni-Dhanesha H; Alsulami, Meshal; Shankar, Adarsh; Achyut, Bhagelu R; Angara, Kartik; Rashid, Mohammad H; Iskander, Asm; Borin, Thaiz F; Wenbo, Zhi; Ara, Roxan; Ali, Meser M; Lebedyeva, Iryna; Chwang, Wilson B; Guo, Austin; Bagher-Ebadian, Hassan; Arbab, Ali S

    2017-01-31

    Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM. Administration of a single IV dose resulted in 7-fold higher levels of HET0016 in plasma and 3.6-fold higher levels in tumor at 60 min than that in IP route. IV treatment with HPßCD-HET0016 decreased tumor growth, and altered vascular kinetics in early and late treatment groups (p < 0.05). Similar growth inhibition was observed in syngeneic GL261 GBM (p < 0.05). Survival studies using patient derived xenografts of GBM811, showed prolonged survival to 26 weeks in animals treated with focal radiation, in combination with HET0016 and TMZ (p < 0.05). We observed reduced expression of markers of cell proliferation (Ki-67), decreased neovascularization (laminin and αSMA), in addition to inflammation and angiogenesis markers in the treatment group (p < 0.05). Our results indicate that HPßCD-HET0016 is effective in inhibiting tumor growth through decreasing proliferation, and neovascularization. Furthermore, HPßCD-HET0016 significantly prolonged survival in PDX GBM811 model.

  2. Repeated intravenous injection of recombinant human hepatocyte growth factor ameliorates liver cirrhosis but causes albuminuria in rats.

    PubMed

    Kusumoto, Kazunori; Ido, Akio; Moriuchi, Akihiro; Katsura, Toshiya; Kim, Ildeok; Takahama, Yuka; Numata, Masatsugu; Kodama, Mayumi; Hasuike, Satoru; Nagata, Kenji; Uto, Hirofumi; Inui, Ken-Ichi; Tsubouchi, Hirohito

    2006-03-01

    Hepatocyte growth factor (HGF) is a promising agent for the treatment of liver cirrhosis because of its mitogenic and anti-fibrotic effects. We investigated the effect of recombinant human HGF (rh-HGF) on cirrhosis development; its pharmacokinetics and nephrotoxicity in rats with liver cirrhosis induced by 4-week treatment with dimethylnitrosamine (DMN). rh-HGF (0.3 mg/kg) was intravenously administered to rats once a day for 4 weeks in parallel with DMN treatment or twice a day for the last 2 weeks of DMN treatment. Repeated doses of rh-HGF increased the liver weight and serum albumin, and reduced serum ALT. The development of hepatic fibrosis was inhibited more efficiently by extended low-dose treatment with rh-HGF. In cirrhotic rats, serum levels of rh-HGF increased and clearance was decreased, leading to an increase in the area under the plasma-concentration time curve and a decrease in the steady-state volume of distribution. Repeated doses of rh-HGF led to increased urinary albumin excretion, but no rh-HGF-treated animals developed increased serum creatinine levels. Urinary albumin excretion returned to baseline after the cessation of rh-HGF. These results suggest that extended treatment with rh-HGF is required for the attenuation of cirrhosis, and repeated doses of rh-HGF cause adverse effects in extra-hepatic organs. These issues must be resolved before the widespread application of rh-HGF in the treatment of liver cirrhosis.

  3. Intravenous Formulation of HET0016 Decreased Human Glioblastoma Growth and Implicated Survival Benefit in Rat Xenograft Models

    PubMed Central

    Jain, Meenu; Gamage, Nipuni-Dhanesha H.; Alsulami, Meshal; Shankar, Adarsh; Achyut, Bhagelu R.; Angara, Kartik; Rashid, Mohammad H.; Iskander, Asm; Borin, Thaiz F.; Wenbo, Zhi; Ara, Roxan; Ali, Meser M.; Lebedyeva, Iryna; Chwang, Wilson B.; Guo, Austin; Bagher-Ebadian, Hassan; Arbab, Ali S.

    2017-01-01

    Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM. Administration of a single IV dose resulted in 7-fold higher levels of HET0016 in plasma and 3.6-fold higher levels in tumor at 60 min than that in IP route. IV treatment with HPßCD-HET0016 decreased tumor growth, and altered vascular kinetics in early and late treatment groups (p < 0.05). Similar growth inhibition was observed in syngeneic GL261 GBM (p < 0.05). Survival studies using patient derived xenografts of GBM811, showed prolonged survival to 26 weeks in animals treated with focal radiation, in combination with HET0016 and TMZ (p < 0.05). We observed reduced expression of markers of cell proliferation (Ki-67), decreased neovascularization (laminin and αSMA), in addition to inflammation and angiogenesis markers in the treatment group (p < 0.05). Our results indicate that HPßCD-HET0016 is effective in inhibiting tumor growth through decreasing proliferation, and neovascularization. Furthermore, HPßCD-HET0016 significantly prolonged survival in PDX GBM811 model. PMID:28139732

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

    PubMed Central

    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

  5. Pharmacokinetics of catechols in human subjects intravenously receiving XueBiJing injection, an emerging antiseptic herbal medicine.

    PubMed

    Li, Xiuxue; Cheng, Chen; Wang, Fengqing; Huang, Yühong; Jia, Weiwei; Olaleye, Olajide E; Li, Meijuan; Li, Yanfen; Li, Chuan

    2016-02-01

    XueBiJing injection, prepared from a five-herb combination, is extensively used as add-on therapy in routine sepsis care in China. Catechols, derived from the component herb Salvia miltiorrhiza roots (Danshen), are probably important because of their reported antiseptic properties. This study was designed to characterize pharmacokinetics of major circulating Danshen catechols in human subjects intravenously receiving the injection at the label doses. A total of 17 Danshen catechols were detected in XueBiJing injection (content level, 0.1-139.3 μmol/L). After dosing, tanshinol and salvianolic acid B exhibited relatively high levels of systemic exposure with mean elimination half-lives of 0.38 and 0.29 h, respectively. The total plasma clearance and apparent volume of distribution at steady state of tanshinol were 1.07 L/h/kg and 0.40 L/kg, respectively, whereas those of salvianolic acid B were 0.43 L/h/kg and 0.13 L/kg, respectively. Protocatechuic acid and five other catechols were also detected in plasma but at low exposure levels. Although protocatechuic aldehyde had the highest content level in the injection, like the remaining eight catechols, it was undetected in plasma. Protocatechuic aldehyde was extensively converted into protocatechuic acid and other metabolites. The information gained here facilitates understanding the roles of Danshen catechols in therapeutic actions of XueBiJing injection.

  6. Regression of atherosclerosis by the intravenous infusion of specific biochemical nutrient substrates in animals and humans.

    PubMed Central

    Dudrick, S J

    1987-01-01

    Preliminary studies in 400 New Zealand albino rabbits produced a reliable animal model of nutrient-induced atherosclerosis that simulated that observed in humans. Atherosclerosis was then induced in an additional 1600 rabbits in sets of 40 animals each, maintaining plasma cholesterol concentrations between 1000 and 2000 mg/dL for 6-20 weeks. In each set, 10 control rabbits were killed to document baseline atherosclerosis, and the other 30 rabbits were assigned randomly to one of three groups of 10 rabbits. Groups of 10 rabbits were either continued on the atherogenic diet (group I), given standard laboratory rabbit pellets (group II), or infused continuously with specially formulated anticholesterol solutions via central venous catheters (group III) for 6 weeks. At autopsy, atherosclerotic lesions consistently involved 85-95% of the aorta in group I. In group II, atherosclerosis was comparable with the baseline control group with no regression. In group III, regression of atherosclerosis by 90-95% was consistently documented. Correlations between plasma amino acids and plasma cholesterol concentrations were established in four humans with severe atherosclerosis to maximize the cholesterol reduction capacity of the amino acid formulation. Infusion of the modified total parenteral nutrition solution induced prompt reduction in plasma cholesterol levels by 40-60% regardless of the initial level and was accompanied by evidence of regression of atherosclerosis after a 90-day infusion therapy period. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 13. Fig. 14. Fig. 15. Fig. 16. Fig. 18. Fig. 19. Fig. 20. PMID:3115205

  7. CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing

    PubMed Central

    Clark, Andrew J.; Wiley, Devin T.; Zuckerman, Jonathan E.; Webster, Paul; Chao, Joseph; Lin, James; Yen, Yun; Davis, Mark E.

    2016-01-01

    Nanoparticle-based therapeutics are being used to treat patients with solid tumors. Whereas nanoparticles have been shown to preferentially accumulate in solid tumors of animal models, there is little evidence to prove that intact nanoparticles localize to solid tumors of humans when systemically administered. Here, tumor and adjacent, nonneoplastic tissue biopsies are obtained through endoscopic capture from patients with gastric, gastroesophageal, or esophageal cancer who are administered the nanoparticle CRLX101. Both the pre- and postdosing tissue samples adjacent to tumors show no definitive evidence of either the nanoparticle or its drug payload (camptothecin, CPT) contained within the nanoparticle. Similar results are obtained from the predosing tumor samples. However, in nine of nine patients that were evaluated, CPT is detected in the tumor tissue collected 24–48 h after CRLX101 administration. For five of these patients, evidence of the intact deposition of CRLX101 nanoparticles in the tumor tissue is obtained. Indications of CPT pharmacodynamics from tumor biomarkers such as carbonic anhydrase IX and topoisomerase I by immunohistochemistry show clear evidence of biological activity from the delivered CPT in the posttreatment tumors. PMID:27001839

  8. Integration of preclinical and clinical knowledge to predict intravenous PK in human: bilastine case study.

    PubMed

    Vozmediano, Valvanera; Ortega, Ignacio; Lukas, John C; Gonzalo, Ana; Rodriguez, Monica; Lucero, Maria Luisa

    2014-03-01

    Modern pharmacometrics can integrate and leverage all prior proprietary and public knowledge. Such methods can be used to scale across species or comparators, perform clinical trial simulation across alternative designs, confirm hypothesis and potentially reduce development burden, time and costs. Crucial yet typically lacking in integration is the pre-clinical stage. Prediction of PK in man, using in vitro and in vivo studies in different animal species, is increasingly well theorized but could still find wider application in drug development. The aim of the present work was to explore methods for bridging pharmacokinetic knowledge from animal species (i.v. and p.o.) and man (p.o.) into i.v. in man using the antihistamine drug bilastine as example. A model, predictive of i.v. PK in man, was developed on data from two pre-clinical species (rat and dog) and p.o. in man bilastine trials performed earlier. In the knowledge application stage, two different approaches were used to predict human plasma concentration after i.v. of bilastine: allometry (several scaling methods) and a semi-physiological method. Both approaches led to successful predictions of key i.v. PK parameters of bilastine in man. The predictive i.v. PK model was validated using later data from a clinical study of i.v. bilastine. Introduction of such knowledge in development permits proper leveraging of all emergent knowledge as well as quantification-based exploration of PK scenario, e.g. in special populations (pediatrics, renal insufficiency, comedication). In addition, the methods permit reduction or elimination and certainly optimization of learning trials, particularly those concerning alternative off-label administration routes.

  9. Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease

    PubMed Central

    2012-01-01

    Background Human intravenous immunoglobulin (hIVIG) preparation is indicated for treating primary immunodeficiency disorders associated with impaired humoral immunity. hIVIG is known for its anti-inflammatory properties and a decent safety profile. Therefore, by virtue of its constituent natural anti-amyloid beta antibodies and anti-inflammatory effects, hIVIG is deemed to mediate beneficial effects to patients of Alzheimer’s disease (AD). Here, we set out to explore the effects of hIVIG in a mouse model of AD. Methods We treated APP/PS1dE9 transgenic and wild-type mice with weekly injections of a high hIVIG dose (1 g/kg) or saline for 3 or 8 months. Treatment effect on brain amyloid pathology and microglial reactivity was assessed by ELISA, immunohistochemistry, RT-PCR, and confocal microscopy. Results We found no evidence for reduction in Aβ pathology; instead 8 months of hIVIG treatment significantly increased soluble levels of Aβ40 and Aβ42. In addition, we noticed a significant reduction in CD45 and elevation of Iba-1 markers in specific sub-populations of microglial cells. Long-term hIVIG treatment also resulted in significant suppression of TNF-α and increase in doublecortin positive adult-born neurons in the dentate gyrus. Conclusions Our data indicate limited ability of hIVIG to impact amyloid burden but shows changes in microglia, pro-inflammatory gene expression, and neurogenic effects. Immunomodulation by hIVIG may account for its beneficial effect in AD patients. PMID:22642812

  10. Intracerebral and Intravenous Transplantation Represents a Favorable Approach for Application of Human Umbilical Cord Mesenchymal Stromal Cells in Intracerebral Hemorrhage Rats

    PubMed Central

    Xie, Jiang; Wang, Bin; Wang, Lian; Dong, Fang; Bai, Gang; Liu, Yongjun

    2016-01-01

    Background Intracerebral hemorrhage (ICH) is one severe subtype of stroke, with a very complex pathology. Stem cell-based therapy holds promising potential in the treatment of neurological disorders. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) have a therapeutic effect in recovery from brain damage following ICH. The aim of this study was to identify an effective and convenient way of using UC-MSCs in the ICH rat model. Material/Methods CM-DiI-labeled human UC-MSCs were transplanted intracerebrally or intravenously into collagenase VII-induced ICH rat models. Neurological function was evaluated before ICH and at 0, 7, 14, 21, and 28 days after treatment. ICH rats were sacrificed to evaluate the injury volume. Neurogenesis and angiogenesis and vascular areas were investigated using microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and 4′,6-diamidino-2-phenylindole (DAPI) immunohistochemistry at two weeks after transplantation. Results The intracerebral and intravenous administration of UC-MSCs both resulted in significant improvement in neurological function and decrease in injury volume of ICH rats. Transplanted UC-MSCs were chemotactic in vivo and showed a predominant distribution around the ICH region. In addition, UC-MSCs could integrate into the cerebral vasculature in both groups. Conclusions Both intracerebral and intravenous administration of UC-MSCs could have a favorable effect on recovery of neurological function in ICH rats, although the fundamental mechanisms may be different between the two groups. Our data suggest that intravenous implantation of UC-MSCs could serve as a favorable approach for cell-based therapy in central nervous system (CNS) diseases according to clinical needs. PMID:27703134

  11. Intravenous and oral zidovudine pharmacokinetics and coagulation effects in asymptomatic human immunodeficiency virus-infected hemophilia patients.

    PubMed Central

    Morse, G D; Portmore, A C; Marder, V; Plank, C; Olson, J; Taylor, C; Bonnez, W; Reichman, R C

    1992-01-01

    Pharmacokinetic and coagulation studies were carried out over a 12-week period with 11 asymptomatic hemophilia patients with human immunodeficiency virus infection receiving zidovudine (ZDV). The patients received 300 mg every 4 h while awake (the accepted dose at the time of this study); consecutive 24-h intravenous (i.v.) and 12-h oral pharmacokinetic studies were conducted at weeks 1, 6, and 12. Coagulation studies were conducted at weeks 0, 4, 8, and 12. The numbers of units of factors VIII and IX and cryoprecipitate transfused during the 12-week periods before, during, and after ZDV treatment were recorded. Following i.v. and oral ZDV administration, the concentration in plasma declined rapidly over the first 4 h, and in some patients, ZDV was still detectable at 4 to 10 h. The i.v. total clearances (means +/- standard deviations) were 14.9 +/- 7.3, 11.2 +/- 3.7, and 15.1 +/- 4.7 ml/min/kg of body weight. The i.v. distribution volumes were 1.08 +/- 0.5, 1.0 +/- 0.4, and 1.65 +/- 1.4 liters/kg. The bioavailabilities were 0.54 +/- 0.22, 0.46 +/- 0.19, and 0.59 +/- 0.13 at weeks 1, 6, and 12, respectively. The pattern of ZDV-glucuronide (GZDV) disposition was similar to that of ZDV, and the peak plasma GZDV-to-ZDV ratio was higher after oral dosing, consistent with first-pass metabolism. In some individuals, up to 33% of an i.v. dose was excreted unchanged. At weeks 6 and 12, greater than 300 mg of total ZDV (GZDV plus ZDV) was recovered in the urine of some patients, suggesting tissue redistribution. Concentration in plasma after oral ZDV administration were variable, both within and between patients. The von Willebrand antigen level consistently decreased throughout the study but was not accompanied by a parallel change in ristocetin cofactor A activity, and no clinical adverse effects on coagulation were noted. This study demonstrates that ZDV can be used in hemophilia patients without worsening of their bleeding tendencies. The clinical significance of

  12. A supersulfated low-molecular-weight heparin (IK-SSH) increases plasma levels of free and total tissue factor pathway inhibitor after intravenous and subcutaneous administration in humans.

    PubMed

    Kaiser, B; Glusa, E; Hoppensteadt, D A; Breddin, H K; Amiral, J; Fareed, J

    1998-09-01

    Unfractionated as well as low-molecular-weight heparins (LMWH) are known to cause an increase in blood levels of tissue factor pathway inhibitor (TFPI). To study the effect of a newly developed supersulfated LMWH (IK-SSH, Iketon Farmaceutici) on TFPI concentrations in human plasma, the compound was injected into volunteers at doses of 0.14, 0.33 and 0.66 mg/kg intravenously or 0.33, 0.66 and 1.0 mg/kg subcutaneously. At certain known times blood was drawn and plasma levels of both total and free TFPI were measured using enzyme-linked immunosorbent assay methodology. Baseline plasma concentrations of TFPI were 72.2+/-3.1 ng/ml for total and 10.8+/-0.8 ng/ml for free TFPI. Intravenous or subcutaneous injection of IK-SSH led to a strong and long-lasting rise in TFPI levels which were increased more than 5-fold for total TFPI and more than 30-fold for free TFPI. Maximum TFPI levels were reached 5-10 min after intravenous and 60 min after subcutaneous administration. IK-SSH caused prolongation of ex-vivo clotting times in the APTT and Heptest assay, whereas thrombin time was not affected. Anticoagulant actions of IK-SSH showed a significant correlation to plasma concentrations of TFPI and they are thought to be based at least partially on the release of TFPI from vascular sites.

  13. Cardiovascular responses to intravenous administration of human hemokinin-1 and its truncated form hemokinin-1(4-11) in anesthetized rats.

    PubMed

    Kong, Zi-Qing; Fu, Cai-Yun; Chen, Qiang; Wang, Rui

    2008-08-20

    Human hemokinin-1 and its carboxy-terminal fragment human hemokinin-1(4-11) have been recently identified as the members of the tachykinin family. The peripheral cardiovascular effects of these two tachykinin peptides were investigated in anesthetized rats. Lower doses of human hemokinin-1 (0.1-3 nmol/kg) injected intravenously (i.v.) induced depressor response, whereas higher doses (10 and 30 nmol/kg) caused biphasic (depressor and pressor) responses. The depressor response is primarily due to the action on endothelial tachykinin NK(1) receptor to release endothelium-derived relaxing factor (NO) and vagal reflex was absent in this modulation. The pressor response is mediated through the activation of tachykinin NK(1) receptor to release catecholamines from sympathetic ganglia and adrenal medulla. Moreover, human hemokinin-1 injected i.v. produced a dose-dependent tachycardia response along with blood pressure responses and the activation of sympathetic ganglia and adrenal medulla are involved in the tachycardia response. Human hemokinin-1(4-11) only lowered mean arterial pressure dose-dependently (0.1-30 nmol/kg) and the mechanisms involved in the depressor response are similar to that of human hemokinin-1. Additionally, human hemokinin-1(4-11) could also produce tachycardia response dose-dependently and the mechanisms involved in the tachycardia response are similar to that of human hemokinin-1 except that bilateral adrenalectomy could not affect the tachycardia markedly, indicating that the tachycardia induced by human hemokinin-1(4-11) is primarily due to the stimulation of sympathetic ganglia. In a word, to a certain extent, human hemokinin-1(4-11) is the active fragment of human hemokinin-1, however, the differences between human hemokinin-1 and hemokinin-1(4-11) involved in the effects of cardiovascular system suggest that the divergent amino acid residues at the N-terminus of human hemokinin-1 produced different activation properties for tachykinin NK(1

  14. Intravenous anaesthesia in goats: a review.

    PubMed

    Dzikiti, T Brighton

    2013-02-13

    Intravenous anaesthesia is gradually becoming popular in veterinary practice. Traditionally, general anaesthesia is induced with intravenous drugs and then maintained with inhalation agents. Inhalation anaesthetic agents cause more significant dose-dependent cardiorespiratory depression than intravenous anaesthetic drugs, creating a need to use less of the inhalation anaesthetic agents for maintenance of general anaesthesia by supplementing with intravenous anaesthesia drugs. Better still, if anaesthesia is maintained completely with intravenous anaesthetic drugs, autonomic functions remain more stable intra-operatively. Patient recovery from anaesthesia is smoother and there is less pollution of the working environment than happens with inhalation anaesthetic agents. Recently, a number of drugs with profiles (pharmacokinetic and pharmacodynamic) suitable for prolonged intravenous anaesthesia have been studied, mostly in humans and, to a certain extent, in dogs and horses. There is currently very little scientific information on total intravenous anaesthesia in goats, although, in the past few years, some scholarly scientific articles on drugs suitable for partial intravenous anaesthesia in goats have been published. This review article explored the information available on drugs that have been assessed for partial intravenous anaesthesia in goats, with the aim of promoting incorporation of these drugs into total intravenous anaesthesia protocols in clinical practice. That way, balanced anaesthesia, a technique in which drugs are included in anaesthetic protocols for specific desired effects (hypnosis, analgesia, muscle relaxation, autonomic stabilisation) may be utilised in improving the welfare of goats undergoing general anaesthesia.

  15. Rechallenge with intravenous recombinant human erythropoietin can be successful following the treatment of anti-recombinant erythropoietin associated pure red cell aplasia.

    PubMed

    Praditpornsilpa, Kearkiat; Tiranathanakul, Khajohn; Jootar, Saengsuree; Tungsanga, Kriang; Eiam-Ong, Somchai

    2014-05-01

    Anti recombinant human erythropoietin (r-HuEpo) associated pure red cell aplasia (PRCA) is an immunologic adverse effect of using subcutaneous r-HuEpo. Immunosuppressive agents have been suggested as treatment of this serious complication. After the reversal of anti-r-HuEpo antibody, the patients continue to have renal anemia and require long-term blood transfusion, albeit less frequently than when the antibody is positive. It is controversial whether re-challenging the patients with r-HuEpo is appropriate because re-challenging may cause the reappearance of the antibody. To balance the risk of antir-HuEpo antibody reappearance and longterm blood transfusion complications, we re-challenged r-HuEpo in five anti-r-HuEpo associated PRCA cases after a successful reversal of antibody using prednisolone in combination with cyclophosphamide. The rechallenge was performed intravenously since there were no reports of anti-r-HuEpo associated PRCA cases using this administration route. The duration after the reversal of antibody was 2.4 months before the re-challenge. Two patients were immediately re-challenged as soon as the antibodies reversed. After rechallenge with intravenous r-HuEpo, all patients responded to r-HuEpo: target level of Hb was maintained, blood transfusion was not required, and anti-r-HuEpo was consistently negative. All patients were followed for at least 6 months after re-challenge. Our data suggest that re-challenge with intravenous r-HuEpo can successfully treat anti- r-HuEpo associated PRCA.

  16. Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

    PubMed Central

    Lee, JooBuom; Lee, Kyungsun; Choe, Keunbum; Jung, Hyunseob; Cho, Hyunseok; Choi, Kiseok; Kim, Taegon; Kim, Seojin; Lee, Hyeong-Seok; Cha, Mi-Jin; Song, Si-Whan; Lee, Chul Kyu; Chun, Gie-Taek

    2015-01-01

    TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats. PMID:26877840

  17. Human neuroblastoma cell growth in xenogeneic hosts: comparison of T cell-deficient and NK-deficient hosts, and subcutaneous or intravenous injection routes.

    PubMed

    Turner, W J; Chatten, J; Lampson, L A

    1990-04-01

    We have examined two features of neuroblastoma cells that had not been well-characterized in a xenogeneic model: The cells display unusual immunologic properties in other experimental systems, and the original tumors display widespread and characteristic patterns of metastasis. To determine the most appropriate immunodeficient host for primary tumor growth, T cell-deficient nude mice, NK-deficient beige mice, beige-nudes, and controls were injected with the well-characterized line CHP-100. To define the pattern of tumor spread, complete autopsies were performed following subcutaneous, intraperitoneal and intravenous injections. CHP-100 consistently formed subcutaneous tumors in T cell-deficient mice (nude and beige-nude), but not in T cell-competent mice (beige, heterozygous nu/+ and bg/+, or wild-type). The growth rate and final size of the subcutaneous tumors were not greater in beige-nudes than in nudes. All mice showed early CHP-100 cell death after subcutaneous injection; the nature of the immunodeficiency was more relevant for the surviving subpopulation. Widespread dissemination was seen following intravenous injection, particularly in beige-nudes. Aspects of the growth patterns were appropriate to the tumor of origin. The behavior in immunodeficient mice suggests that T cells can play a role in controlling the growth of these cells; the next steps will be to define the effector mechanisms, and to determine if they can be exploited for human patients. The hematogenous spread following intravenous injection suggests that insights into the control of blood-borne tumor may also come from further study of this model.

  18. Pharmacokinetics of oral cefetamet pivoxil (Ro 15-8075) and intravenous cefetamet (Ro 15-8074) in humans: a review.

    PubMed

    Stoeckel, K; Tam, Y K; Kneer, J

    1989-01-01

    Cefetamet pivoxil belongs to the class of orally absorbed pro-drug esters which are hydrolyzed to the active compound (cefetamet) on their first pass through the gut wall and/or the liver. The intravenously administered cefetamet is eliminated predominantly unchanged in the urine by glomerular filtration. Systemic and renal clearance values for cefetamet were 140 and 130 ml/min, respectively. The plasma protein binding is 22%, whereby the only binding protein is albumin. The steady state volume of distribution (0.29 l/kg) corresponds roughly to the extracellular water space which is consistent with other low protein-bound cephalosporins. In general, after intravenous doses, cefetamet follows the kinetic behaviour of a cephalosporin with low protein binding, limited non-renal clearance, and renal clearance that is predominantly due to glomerular filtration, e.g. ceftizoxime, ceftazidime. After oral administration, cefetamet pivoxil shows a significant food effect (F = 41% vs 51%). Hence, cefetamet pivoxil is recommended to be taken after food. The food effect, however, is not of such a magnitude that it will be of clinical consequence when this recommendation is not followed. The food effect is not related to a change in gastric pH because antacids and ranitidine do not affect the absorption of cefetamet pivoxil, although in approximately 20% of the subjects absorption of the drug is delayed. The elimination of cefetamet is directly proportional to renal function. In patients with varying degrees of renal insufficiencies, dosage should be decreased accordingly. Age has no effect on the bioavailability of cefetamet pivoxil. However, the clearance of cefetamet is higher in children and lower in the elderly.

  19. Distribution of human umbilical cord blood-derived mesenchymal stem cells in the Alzheimer's disease transgenic mouse after a single intravenous injection.

    PubMed

    Park, Sang Eon; Lee, Na Kyung; Lee, Jeongmin; Hwang, Jung Won; Choi, Soo Jin; Hwang, Hyeri; Hyung, Brian; Chang, Jong Wook; Na, Duk L

    2016-03-02

    The aim of this study was to track the migration of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) administered through a single intravenous injection and to observe the consequential therapeutic effects in a transgenic Alzheimer's disease mouse model. Ten-month-old APP/PS1 mice received a total injection of 1×10 cells through the lateral tail vein and were killed 1, 4, and 7 days after administration. On the basis of immunohistochemical analysis, hUCB-MSCs were not detected in the brain at any of the time points. Instead, most of the injected mesenchymal stem cells were found to be distributed in the lung, heart, and liver. In terms of the molecular effects, statistically significant differences in the amyloid β protein, neprilysin, and SOX2 levels were not observed among the groups. On the basis of the results from this study, we suggest that single intravenously administered hUCB-MSCs are not delivered to the brain and also do not have a significant influence on Alzheimer's disease pathology.

  20. Pharmacokinetics of 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (CTHC) after intravenous administration of CTHC in healthy human subjects.

    PubMed

    Glaz-Sandberg, A; Dietz, L; Nguyen, H; Oberwittler, H; Aderjan, Rolf; Mikus, Gerd

    2007-07-01

    After cannabis consumption there is only limited knowledge about the pharmacokinetic (PK) and metabolic properties of 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (CTHC), which is formed by oxidative breakdown from Delta(9)-tetrahydrocannabinol (THC). Despite widely-varying concentrations observed in smoking studies, attempts have been made to interpret consumption behavior with special regard to a cumulated or decreasing concentration of CTHC in serum. Ten healthy nonsmoking white male individuals received 5 mg CTHC intravenously over 10 min. Highest serum concentrations of CTHC were observed at the end of the infusion (336.8+/-61.7 microg/l) followed by a quick decline. CTHC concentration could be quantified up to 96 h after administration, with a terminal elimination half-life of 17.6+/-5.5 h. Total clearance was low (91.2+/-24.0 ml/min), with renal clearance having only a minor contribution (0.136+/-0.094 ml/min). This first metabolite-based kinetic approach will allow an advanced understanding of CTHC PKs data obtained in previous studies with THC.

  1. Hepatitis C virus dynamics and cellular gene expression in uPA-SCID chimeric mice with humanized livers during intravenous silibinin monotherapy

    SciTech Connect

    DebRoy, Swati; Hiraga, Nobuhiko; Imamura, Michio; Hayes, C. Nelson; Akamatsu, Sakura; Canini, Laetitia; Perelson, Alan S.; Pohl, Ralf T.; Persiani, Stefano; Uprichard, Susan L.; Tateno, Chise; Dahari, Harel; Chayama, Kazuaki

    2016-06-08

    Legalon SIL (SIL) is a chemically hydrophilized version of silibinin, an extract of milk thistle (Silybum marianum) seeds that has exhibited hepatoprotective and antiviral effectiveness against hepatitis C virus (HCV) in patients leading to viral clearance in combination with ribavirin. In this paper, to elucidate the incompletely understood mode of action of SIL against HCV, mathematical modelling of HCV kinetics and human hepatocyte gene expression studies were performed in uPA-SCID-chimeric mice with humanized livers. Chronically HCV-infected mice (n = 15) were treated for 14 days with daily intravenous SIL at 469, 265 or 61.5 mg/kg. Serum HCV and human albumin (hAlb) were measured frequently, and liver HCV RNA was analysed at days 3 and 14. Microarray analysis of human hepatocyte gene expression was performed at days 0, 3 and 14 of treatment. While hAlb remained constant, a biphasic viral decline in serum was observed consisting of a rapid 1st phase followed by a second slower phase (or plateau with the two lower SIL dosings). SIL effectiveness in blocking viral production was similar among dosing groups (median ε = 77%). However, the rate of HCV-infected hepatocyte decline, δ, was dose-dependent. Intracellular HCV RNA levels correlated (r = 0.66, P = 0.01) with serum HCV RNA. Pathway analysis revealed increased anti-inflammatory and antiproliferative gene expression in human hepatocytes in SIL-treated mice. Finally, the results suggest that SIL could lead to a continuous second-phase viral decline, that is potentially viral clearance, in the absence of adaptive immune response along with increased anti-inflammatory and antiproliferative gene expression in human hepatocytes.

  2. Hepatitis C virus dynamics and cellular gene expression in uPA-SCID chimeric mice with humanized livers during intravenous silibinin monotherapy

    DOE PAGES

    DebRoy, Swati; Hiraga, Nobuhiko; Imamura, Michio; ...

    2016-06-08

    Legalon SIL (SIL) is a chemically hydrophilized version of silibinin, an extract of milk thistle (Silybum marianum) seeds that has exhibited hepatoprotective and antiviral effectiveness against hepatitis C virus (HCV) in patients leading to viral clearance in combination with ribavirin. In this paper, to elucidate the incompletely understood mode of action of SIL against HCV, mathematical modelling of HCV kinetics and human hepatocyte gene expression studies were performed in uPA-SCID-chimeric mice with humanized livers. Chronically HCV-infected mice (n = 15) were treated for 14 days with daily intravenous SIL at 469, 265 or 61.5 mg/kg. Serum HCV and human albuminmore » (hAlb) were measured frequently, and liver HCV RNA was analysed at days 3 and 14. Microarray analysis of human hepatocyte gene expression was performed at days 0, 3 and 14 of treatment. While hAlb remained constant, a biphasic viral decline in serum was observed consisting of a rapid 1st phase followed by a second slower phase (or plateau with the two lower SIL dosings). SIL effectiveness in blocking viral production was similar among dosing groups (median ε = 77%). However, the rate of HCV-infected hepatocyte decline, δ, was dose-dependent. Intracellular HCV RNA levels correlated (r = 0.66, P = 0.01) with serum HCV RNA. Pathway analysis revealed increased anti-inflammatory and antiproliferative gene expression in human hepatocytes in SIL-treated mice. Finally, the results suggest that SIL could lead to a continuous second-phase viral decline, that is potentially viral clearance, in the absence of adaptive immune response along with increased anti-inflammatory and antiproliferative gene expression in human hepatocytes.« less

  3. Development of antihuman IgG antibodies and hematologic deficits but not clinical abnormalities in C57BL/6 mice after repeated administration of human intravenous immunoglobulin.

    PubMed

    Loeffler, David A; Smith, Lynnae M; Klaver, Andrea C; Brzezinski, Heather A; Morrison, Essie I; Coffey, Mary P; Steficek, Barbara A; Cook, Susan S

    2012-02-01

    Intravenous immunoglobulin (IvIg) preparations consist of purified human immunoglobulins collected from large numbers of healthy persons and are used to treat autoimmune, immunodeficiency, and inflammatory disorders. Studying the effects of IvIg effects in experimental animal models might clarify its mechanisms of action in these disorders, but whether 'serum sickness' or other abnormalities occur after repeated IvIg administration to immunocompetent animals is unknown. In the current study, male C57BL/6 mice (8 to 10 wk old; n = 27) received IvIg (1 g/kg IP) weekly for 6 wk. They were observed for clinical abnormalities, and body weight, temperature, renal function, hematologic parameters, and serum antihuman IgG antibodies were measured before and during treatment. Postmortem evaluations were performed on kidney, spleen, liver, and heart. No clinical or histologic abnormalities were noted despite a transient increase in BUN. Mean antibody levels to human IgG on days 21 and 43 after IvIg administration were increased by 23-fold compared with pretreatment levels. 88% and 89% of the mice were antibody responders on those days. Unexpectedly, hemoglobin, hematocrit, and RBC, WBC, lymphocyte, and platelet counts decreased after IvIg administration. These findings suggest that although it does not produce serum sickness, repeated IvIg administration to immunocompetent mice induces a strong humoral immune response and hematologic deficits of unknown etiology. These factors could cause the effects of IvIg preparations in mouse models of human disease to differ from their effects in the human disorders.

  4. Intravenous paracetamol (acetaminophen).

    PubMed

    Duggan, Sean T; Scott, Lesley J

    2009-01-01

    Intravenous paracetamol (rINN)/intravenous acetaminophen (USAN) is an analgesic and antipyretic agent, recommended worldwide as a first-line agent for the treatment of pain and fever in adults and children. In double-blind clinical trials, single or multiple doses of intravenous paracetamol 1 g generally provided significantly better analgesic efficacy than placebo treatment (as determined by primary efficacy endpoints) in adult patients who had undergone dental, orthopaedic or gynaecological surgery. Furthermore, where evaluated, intravenous paracetamol 1 g generally showed similar analgesic efficacy to a bioequivalent dose of propacetamol, and a reduced need for opioid rescue medication. In paediatric surgical patients, recommended doses of intravenous paracetamol 15 mg/kg were not significantly different from propacetamol 30 mg/kg for the treatment of pain, and showed equivocal analgesic efficacy compared with intramuscular pethidine 1 mg/kg in several randomized, active comparator-controlled studies. In a randomized, noninferiority study in paediatric patients with an infection-induced fever, intravenous paracetamol 15 mg/kg treatment was shown to be no less effective than propacetamol 30 mg/kg in terms of antipyretic efficacy. Intravenous paracetamol was well tolerated in clinical trials, having a tolerability profile similar to placebo. Additionally, adverse reactions emerging from the use of the intravenous formulation of paracetamol are extremely rare (<1/10 000). [table: see text].

  5. Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors

    PubMed Central

    Koeberl, Dwight D.; Alexander, Ian E.; Halbert, Christine L.; Russell, David W.; Miller, A. Dusty

    1997-01-01

    We previously found that gene transduction by adeno-associated virus (AAV) vectors in cell culture can be stimulated over 100-fold by treatment of the target cells with agents that affect DNA metabolism, such as irradiation or topoisomerase inhibitors. Here we show that previous γ-irradiation increased the transduction rate in mouse liver by up to 900-fold, and the topoisomerase inhibitor etoposide increased transduction by about 20-fold. Similar rates of hepatic transduction were obtained by direct injection of the liver or by systemic delivery via tail vein injection. Hepatocytes were much more efficiently transduced than other cells after systemic delivery, and up to 3% of all hepatocytes could be transduced after one vector injection. The presence of wild-type AAV, which contaminates many AAV vector preparations, was required to observe a full response to γ-irradiation. Injection of mice with AAV vectors encoding human clotting factor IX after γ-irradiation resulted in synthesis of low levels of human clotting factor IX for the 5-month period of observation. These studies show the potential of targeted gene transduction of the liver by AAV vectors for treatment of various hematological or metabolic diseases. PMID:9037069

  6. Validation of an UPLC-MS-MS Method for Quantitative Analysis of Vincristine in Human Urine After Intravenous Administration of Vincristine Sulfate Liposome Injection.

    PubMed

    Yang, Fen; Wang, Hongyun; Hu, Pei; Jiang, Ji

    2015-07-01

    Vincristine sulfate liposome injection (VSLI) is a liposomal formulation of vincristine (VCR) sulfate, being developed for the systemic treatment of cancer. In this paper, we have developed and validated a method to quantify VCR in human urine to obtain the urinary excretion of VCR after intravenous administration of VSLI. The analyte was extracted from urine samples using liquid-liquid extraction after addition of vinblastine (VBL, used as internal standard) and chromatographed on an Acquity UPLC HSS T3 column with a gradient mobile phase at a flow rate of 0.4 mL/min. The multiple reactions monitoring transitions of m/z 413.2 → 353.2 and m/z 406.2 → 271.6 were used to quantify VCR and VBL, respectively. The lower limit of quantification was 0.5 ng/mL with a precision (RSD%) of 5.7% and an accuracy (RE%) of 6.7%. The calibration curve was linear up to 100.0 ng/mL. Intraday precision and accuracy ranged from 0.8 to 11.0% and from -12.4 to 11.3%, respectively. Interassay precision and accuracy ranged from 8.0 to 10.1% and from -7.7 to 3.6%, respectively. No significant matrix effect was observed for VCR. The method was successfully applied for pharmacokinetic study of VSLI to investigate the route and extent of VCR urinary excretion in Chinese subjects with lymphoma.

  7. Local distribution and concentration of intravenously injected sup 131 I-9. 2. 27 monoclonal antibody in human malignant melanoma

    SciTech Connect

    Del Vecchio, S.; Reynolds, J.C.; Carrasquillo, J.A.; Blasberg, R.G.; Neumann, R.D.; Lotze, M.T.; Bryant, G.J.; Farkas, R.J.; Larson, S.M. )

    1989-05-15

    Regional measurements of {sup 131}I-9.2.27 distribution in human melanoma tumors were obtained using quantitative autoradiography. Tumors were removed from patients 72-96 h after they had received an i.v. injection of 9.15 mCi (100 mg) of {sup 131}I-9.2.27. The autoradiographic images showed that the radioactivity reaching the tumor was heterogeneously distributed. Areas of relative high and low uptake were selected in each tumor. Regions of high activity contained from 51 to 1371 nCi/g, while areas with low uptake had radioactivity ranging from 12 to 487 nCi/g. The reliability of the autoradiographic measurements was demonstrated by the strong positive correlation with direct tissue sample counting (r = 0.994 P less than 0.001). Since comparative immunocytochemistry showed a homogeneous and diffuse staining of target antigen on viable tumor cells, variability of monoclonal antibody uptake within individual tumors was not primarily due to heterogeneity of antigen expression in these cases. However, antigen levels accounted for some of the variation from tumor to tumor. When immunoperoxidase staining was repeated on adjacent sections without the addition of 9.2.27, it confirmed the nonuniform distribution of monoclonal antibody found at autoradiography. Thus, quantitative autoradiography gives information about the distribution and the local concentration of radioactive antibody in tumors allowing calculation of the radiation dose delivered to small regions within tumors.

  8. Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats

    PubMed Central

    Cheng, Chen; Lin, Jia-zhen; Li, Li; Yang, Jun-ling; Jia, Wei-wei; Huang, Yu-hong; Du, Fei-fei; Wang, Feng-qing; Li, Mei-juan; Li, Yan-fen; Xu, Fang; Zhang, Na-ting; Olaleye, Olajide E.; Sun, Yan; Li, Jian; Sun, Chang-hai; Zhang, Gui-ping; Li, Chuan

    2016-01-01

    Aim: Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides. Methods: Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro. Results: A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001–2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2–1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular-filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability. Conclusion: Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance. PMID:26838074

  9. Purification of anti-MUC1 antibodies by peptide mimotope affinity chromatography using peptides derived from a polyvalent phage display library.

    PubMed

    Smith, Richard G; Missailidis, Sotiris; Price, Michael R

    2002-01-05

    A polyvalent, lytic phage display system (T7Select415-1b) displaying a random peptide library has been investigated for its ability to discover novel mimotopes reactive with the therapeutic monoclonal antibody C595. Sequence analysis of enriched phage lead to the identification of a predominant sequence RNREAPRGKICS, and two other consensus sequences RXXP and RXP. The novel synthetic peptide RNREAPRGKICS was linked to beaded agarose and the performance as a mimotope affinity chromatography matrix evaluated. Antibody purified using the novel matrix was found to be of higher specific reactivity than antibody purified using the conventional epitope matrix (peptide APDTRPAPG). The RNREAPRGKICS peptide binding to C595 demonstrated a higher equilibrium association constant (K(A)=0.75 x 10(6)) than the epitope peptide (K(A)=0.16 x 10(6)). Circular dichroism showed that the novel peptide had a more highly ordered structure at 4 degrees C and room temperature, than the epitope peptide.

  10. Evaluation of Meropenem Regimens Suppressing Emergence of Resistance in Acinetobacter baumannii with Human Simulated Exposure in an In Vitro Intravenous-Infusion Hollow-Fiber Infection Model

    PubMed Central

    Li, Xin; Wang, Lin; Zhang, Xian-Jia; Yang, Yang; Gong, Wei-Tao; Xu, Bin; Zhu, Ying-Qun

    2014-01-01

    The emergence of resistance to carbapenems in Pseudomonas aeruginosa can be suppressed by optimizing the administration of meropenem. However, whether the same is true for Acinetobacter baumannii is not fully understood. We assessed the bactericidal activity of meropenem and its potency to suppress the emergence of resistance in A. baumannii with human simulated exposure in an in vitro intravenous-infusion hollow-fiber infection model (HFIM). Two clinical strains of carbapenem-susceptible multidrug-resistant A. baumannii (CS-MDRAB), CSRA24 and CSRA91, were used, and their MICs and mutant prevention concentrations (MPCs) were determined. Six meropenem dosage regimens (0.5, 1.0, or 2.0 g given every 8 h [q8h] with a 0.5-h or 3-h infusion for seven consecutive days) were simulated and then evaluated in the HFIM. Both the total population and resistant subpopulations of the two strains were quantified. Drug concentrations were measured by high-performance liquid chromatography. All dosage regimens, except for the lowest dosage (0.5 g for both the 0.5-h and 3-h infusions), showed 3-log CFU/ml bacterial killing. Dosage regimens of 2.0 g with 0.5-h and 3-h infusions exhibited an obvious bactericidal effect and suppressed resistance. Selective amplification of subpopulations with reduced susceptibility to meropenem was suppressed with a percentage of the dosage interval in which meropenem concentrations exceeded the MPC (T>MPC) of ≥20% or with a ratio of T>MPC to the percentage of the dosage interval in which drug concentrations are within the mutant selection window of ≥0.25. Our in vitro data support the use of a high dosage of meropenem (2.0 g q8h) for the treatment of severe infection caused by CS-MDRAB. PMID:25182633

  11. Determination of free and total vincristine in human plasma after intravenous administration of vincristine sulfate liposome injection using ultra-high performance liquid chromatography tandem mass spectrometry.

    PubMed

    Yang, Fen; Wang, Hongyun; Liu, Ming; Hu, Pei; Jiang, Ji

    2013-02-01

    Vincristine sulfate liposome is a liposomal formulation of vincristine sulfate, a traditional anticancer drug, encapsulated in the aqueous core of phospholipid/cholesterol liposomes, which are kinds of targeted carriers to enhance malignancy targeting, exposure and anticancer activity of the drug. To evaluate and compare the pharmacokinetics of nonliposomal and liposome-encapsulated VCR and pharmacodynamic relationships associated with the toxicity and the efficacy behavior, it is essential to have a reliable method of separating the free and liposomal forms of the drug. In this paper, we have developed and validated methods to quantify the free vincristine (F-VCR) and total vincristine (T-VCR) in human plasma after intravenous administration of vincristine sulfate liposome injection (VSLI). The methods involve solid-phase extraction (SPE) for separating the F-VCR and liquid-liquid extraction (LLE) for releasing the VCR totally from the liposomal forms followed by an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). The methods were validated over the concentration range of 0.2-50 ng/mL for F-VCR and 0.5-400 ng/mL for T-VCR, respectively. Inter- and intra-day precision (RSD%) were ≤4.7% for F-VCR and ≤9.8% for T-VCR, respectively. The accuracies were between -2.3 and 9.1% for F-VCR and between -3.2 and 6.9% for T-VCR, respectively. The extraction recovery and the matrix effect were investigated. The methods were successfully applied to the pharmacokinetic study of VSLI in Chinese subjects with lymphoma.

  12. Dose-related modulation of event-related potentials to novel and target stimuli by intravenous Δ⁹-THC in humans.

    PubMed

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

    2012-06-01

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

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

    PubMed Central

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

    2012-01-01

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

  14. Immunoglobulin M-enriched human intravenous immunoglobulins reduce leukocyte-endothelial cell interactions and attenuate microvascular perfusion failure in normotensive endotoxemia.

    PubMed

    Hoffman, Johannes N; Fertmann, Jan M; Vollmar, Brigitte; Laschke, Matthias W; Jauch, Karl W; Menger, Michael D

    2008-01-01

    Clinical studies indicate potential differences in the efficacy of immunoglobulin (Ig) preparations in patients with sepsis. A recent meta-analysis showed improved survival rates with IgM-enriched Igs. It was the objective of the present study to characterize microcirculatory actions of different clinically used Ig preparations in a rodent endotoxin model by intravital microscopy. Male Syrian golden hamsters 6 to 8 weeks old with a body weight of 60 to 80 g were investigated by intravital fluorescence microscopy. Endotoxemia was induced by administration of 2 mg/kg (i.v.) endotoxin (LPS, Escherichia coli). Two different Ig preparations containing IgM, IgA, and IgG (intravenous IgM group; n = 6; 5 mL Pentaglobin/kg body weight, i.v.) or exclusively IgG (intravenous IgG group; n = 5; 5 mL Flebogamma/kg body weight, i.v.) were applied 5 min before LPS. Saline-treated endotoxemic animals served as controls (control; n = 8). In controls, LPS induced massive leukocyte-endothelial cell interactions, pronounced microvascular leakage, a decrease of systemic platelet count, and distinct capillary perfusion failure (P < 0.05). Both intravenous IgM and IgG reduced venular leakage (P< 0.05) and ameliorated the decrease in platelet count (P < 0.05). Of interest, intravenous IgM was capable of significantly (P< 0.05) reducing leukocyte adhesion in venules. This was associated with normalization of capillary perfusion at 24 h of endotoxemia, whereas intravenous IgG could not prevent LPS-mediated microvascular perfusion failure. We demonstrate that IgM-enriched Igs are superior to IgG alone in attenuating LPS-induced leukocytic inflammation and microcirculatory dysfunction. Our findings can explain better efficacy of IgM-enriched Igs in patients with severe sepsis.

  15. Continuous intravenous infusion of ATP in humans yields large expansions of erythrocyte ATP pools but extracellular ATP pools are elevated only at the start followed by rapid declines.

    PubMed

    Rapaport, Eliezer; Salikhova, Anna; Abraham, Edward H

    2015-06-01

    The pharmacokinetics of adenosine 5'-triphosphate (ATP) was investigated in a clinical trial that included 15 patients with advanced malignancies (solid tumors). ATP was administered by continuous intravenous infusions of 8 h once weekly for 8 weeks. Three values of blood ATP levels were determined. These were total blood (erythrocyte) and blood plasma (extracellular) ATP pools along with the initial rate of release of ATP into the blood plasma. We found that values related to erythrocyte ATP pools showed great variability (diversity) among individuals (standard deviation of about 30-40% of mean at baseline). It was discovered that erythrocyte baseline ATP pool sizes are unique to each individual and that they fall within a narrow range in each individual. At the end of an 8 h continuous intravenous infusion of ATP, intracellular erythrocyte ATP pools were increased in the range of 40-60% and extracellular ATP declined from elevated levels achieved at the beginning and middle of the infusion, to baseline levels. The ability of erythrocytes to sequester exogenously administered ATP to this degree, after its initial conversion to adenosine in the blood plasma is unexpected, considering that some of the adenosine is likely to have been degraded by in vivo catabolic activities or taken up by organs. The data suggest that administration of ATP by short-term intravenous infusions, of up to 4 h, may be a favorable way for elevating extracellular ATP pools. A large fraction of the total exogenously administered ATP is sequestered into the intracellular compartments of the erythrocytes after an 8 h intravenous infusion. Erythrocytes loaded with ATP are known to release their ATP pools by the application of previously established agents or conditions applied locally or globally to circulating erythrocytes. Rapid degradation of intravenously administered ATP to adenosine and subsequent accumulation of ATP inside erythrocytes indicate the existence of very effective mechanisms

  16. Community intravenous therapy provision.

    PubMed

    O'Hanlon, Sue; McGrail, Pam; Hodgkins, Paul

    2017-03-08

    Many healthcare services that were once only available in acute settings are now common in the community. Intravenous (IV) therapy is increasingly available as a community service. Given the option, most patients would choose to receive their treatment in a community setting, rather than in hospital. This article describes several outpatient parenteral antimicrobial therapy services, including their advantages and disadvantages. It explores the ways one community NHS trust has developed its community IV therapy service over the past ten years and examines issues pertinent to effective service delivery.

  17. 78 FR 58318 - Clinical Trial Design for Intravenous Fat Emulsion Products; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... HUMAN SERVICES Food and Drug Administration Clinical Trial Design for Intravenous Fat Emulsion Products... ``Clinical Trial Design for Intravenous Fat Emulsion Products.'' This workshop will provide a forum to discuss trial design of clinical trials intended to support registration of intravenous fat...

  18. In vivo transduction by intravenous injection of a lentiviral vector expressing human ADA into neonatal ADA gene knockout mice: a novel form of enzyme replacement therapy for ADA deficiency.

    PubMed

    Carbonaro, Denise A; Jin, Xiangyang; Petersen, Denise; Wang, Xingchao; Dorey, Fred; Kil, Ki Soo; Aldrich, Melissa; Blackburn, Michael R; Kellems, Rodney E; Kohn, Donald B

    2006-06-01

    Using a mouse model of adenosine deaminase-deficient severe combined immune deficiency syndrome (ADA-deficient SCID), we have developed a noninvasive method of gene transfer for the sustained systemic expression of human ADA as enzyme replacement therapy. The method of delivery is a human immunodeficiency virus 1-based lentiviral vector given systemically by intravenous injection on day 1 to 2 of life. In this article we characterize the biodistribution of the integrated vector, the expression levels of ADA enzyme activity in various tissues, as well as the efficacy of systemic ADA expression to correct the ADA-deficient phenotype in this mouse model. The long-term expression of enzymatically active ADA achieved by this method, primarily from transduction of liver and lung, restored immunologic function and significantly extended survival. These studies illustrate the potential for sustained in vivo production of enzymatically active ADA, as an alternative to therapy by frequent injection of exogenous ADA protein.

  19. Immunoglobulin (Ig)G purified from human sera mirrors intravenous Ig human leucocyte antigen (HLA) reactivity and recognizes one's own HLA types, but may be masked by Fab complementarity-determining region peptide in the native sera.

    PubMed

    Ravindranath, M H; Terasaki, P I; Maehara, C Y; Jucaud, V; Kawakita, S; Pham, T; Yamashita, W

    2015-02-01

    Intravenous immunoglobulin (IVIg) reacted with a wide array of human leucocyte antigen (HLA) alleles, in contrast to normal sera, due possibly to the purification of IgG from the pooled plasma. The reactivity of IgG purified from normal sera was compared with that of native sera to determine whether any serum factors mask the HLA reactivity of anti-HLA IgG and whether IgG purified from sera can recognize the HLA types of the corresponding donors. The purified IgG, unlike native sera, mirrored IVIg reactivity to a wide array of HLA-I/-II alleles, indicating that anti-HLA IgG may be masked in normal sera - either by peptides derived from soluble HLA or by those from antibodies. A < 3 kDa peptide from the complementarity-determining region (CDR) of the Fab region of IgG (but not the HLA peptides) masked HLA recognition by the purified IgG. Most importantly, some of the anti-HLA IgG purified from normal sera - and serum IgG from a few donors - indeed recognized the HLA types of the corresponding donors, confirming the presence of auto-HLA antibodies. Comparison of HLA types with the profile of HLA antibodies showed auto-HLA IgG to the donors' HLA antigens in this order of frequency: DPA (80%), DQA (71%), DRB345 (67%), DQB (57%), Cw (50%), DBP (43%), DRB1 (21%), A (14%) and B (7%). The auto-HLA antibodies, when unmasked in vivo, may perform immunoregulatory functions similar to those of therapeutic preparations of IVIg.

  20. Intravenous Fluid Generation System

    NASA Technical Reports Server (NTRS)

    McQuillen, John; McKay, Terri; Brown, Daniel; Zoldak, John

    2013-01-01

    The ability to stabilize and treat patients on exploration missions will depend on access to needed consumables. Intravenous (IV) fluids have been identified as required consumables. A review of the Space Medicine Exploration Medical Condition List (SMEMCL) lists over 400 medical conditions that could present and require treatment during ISS missions. The Intravenous Fluid Generation System (IVGEN) technology provides the scalable capability to generate IV fluids from indigenous water supplies. It meets USP (U.S. Pharmacopeia) standards. This capability was performed using potable water from the ISS; water from more extreme environments would need preconditioning. The key advantage is the ability to filter mass and volume, providing the equivalent amount of IV fluid: this is critical for remote operations or resource- poor environments. The IVGEN technology purifies drinking water, mixes it with salt, and transfers it to a suitable bag to deliver a sterile normal saline solution. Operational constraints such as mass limitations and lack of refrigeration may limit the type and volume of such fluids that can be carried onboard the spacecraft. In addition, most medical fluids have a shelf life that is shorter than some mission durations. Consequently, the objective of the IVGEN experiment was to develop, design, and validate the necessary methodology to purify spacecraft potable water into a normal saline solution, thus reducing the amount of IV fluids that are included in the launch manifest. As currently conceived, an IVGEN system for a space exploration mission would consist of an accumulator, a purifier, a mixing assembly, a salt bag, and a sterile bag. The accumulator is used to transfer a measured amount of drinking water from the spacecraft to the purifier. The purifier uses filters to separate any air bubbles that may have gotten trapped during the drinking water transfer from flowing through a high-quality deionizing cartridge that removes the impurities in

  1. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis: Results from Three Clinical Trials

    PubMed Central

    Østergaard, Mikkel; Taylor, Peter C.; van Vollenhoven, Ronald F.; Chu, Myron; Mallett, Stephen; Perry, Hayley; Kurrasch, Regina

    2016-01-01

    Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development on subcutaneous delivery. Due to differences in study designs and populations, data are summarised separately for each study. Results 483 patients (243, 148 and 92 in OFA110635, OFA110634 and OFA111752 respectively) received up to 7 treatment courses of intravenous ofatumumab; cumulative duration of exposure was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17–47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70/92), serious adverse events for 18% (44/243), 20% (30/148) and 12% (11/92) and serious infections for 3% (8/243), 5% (7/148) and 1% (1/92) of patients in OFA110635, OFA110634 and OFA111752, respectively. The most common adverse events were infusion-related reactions during the first infusion of the first course (48–79%); serious infusion-related reactions were rare (<1% [1/243], 5% [8/148], and 1% [1/92] of patients). Two deaths occurred (fulminant hepatitis B virus infection and interstitial lung disease). Conclusions Ofatumumab was generally well tolerated with no evidence of increased safety risks with multiple retreatments. Serious infections were uncommon and did not increase over time. Trial Registration ClinicalTrials.gov 110635 ClinicalTrials.gov 110634 Clinical

  2. Continued transmission of hepatitis B and C viruses, but no transmission of human immunodeficiency virus among intravenous drug users participating in a syringe/needle exchange program.

    PubMed

    Månsson, A S; Moestrup, T; Nordenfelt, E; Widell, A

    2000-01-01

    The virological efficacy of a syringe/needle exchange program was evaluated in a cohort incidence study. Of 698 intravenous drug users (IVDUs) initially recruited, 15 (2.1%) were HIV-positive at baseline. Adequate follow-up was possible in 515 (74%) and showed no new cases of HIV infection during a median of 31 months. Most IVDUs had been previously exposed to HBV (anti-HBc-positive 70.1%) and HCV (anti-HCV-positive 90.7%). Of those 159 IVDUs negative at baseline for anti-HBc and/or anti-HCV, 56 (35%) seroconverted to one or both viruses during follow-up, corresponding to 11.7 seroconversions/100 y at risk for HBV and 26.3 seroconversions/100 y for HCV. Multiple logistic regression analysis showed hepatitis seroconversion to correlate with imprisonment during the study (OR 2.2; 95% CI 1.04-4.74), absence of drug-free periods (OR 5.7; CI 1.44-22.3) and frequent syringe/needle exchanges (OR 1.31; CI 1.02-1.7). The absence of HIV spread was probably partly due to the low prevalence of HIV-infected IVDUs in the city. Despite free syringes and needles, both HBV and HCV continued to spread at high rates. Nevertheless, syringe/needle exchange programs, coupled with monitoring of serostatus provide good surveillance and are valuable for further assessment of remaining risks.

  3. Intravenous Lipid Emulsions in Parenteral Nutrition123

    PubMed Central

    Fell, Gillian L; Nandivada, Prathima; Gura, Kathleen M; Puder, Mark

    2015-01-01

    Fat is an important macronutrient in the human diet. For patients with intestinal failure who are unable to absorb nutrients via the enteral route, intravenous lipid emulsions play a critical role in providing an energy-dense source of calories and supplying the essential fatty acids that cannot be endogenously synthesized. Over the last 50 y, lipid emulsions have been an important component of parenteral nutrition (PN), and over the last 10–15 y many new lipid emulsions have been manufactured with the goal of improving safety and efficacy profiles and achieving physiologically optimal formulations. The purpose of this review is to provide a background on the components of lipid emulsions, their role in PN, and to discuss the lipid emulsions available for intravenous use. Finally, the role of parenteral fat emulsions in the pathogenesis and management of PN-associated liver disease in PN-dependent pediatric patients is reviewed. PMID:26374182

  4. Comparative removal of solvent and detergent viral inactivating agents from human intravenous immunoglobulin G preparations using SDR HyperD and C18 sorbents.

    PubMed

    Burnouf, Thierry; Sayed, Makram A; Radosevich, Miryana; El-Ekiaby, Magdy

    2009-06-01

    The capacity of hydrophobic octadecyl (C18) and SDR HyperD materials to remove the combination of 1% (v/v) solvent (tri-n-butyl phosphate, TnBP) with 1% (v/v) nonionic detergents (Triton X-100 and Triton X-45) used for viral inactivation of plasma-derived polyvalent intravenous immunoglobulin G (IVIG) preparation has been evaluated. Efficient removal of TnBP (<10 ppm in IVIG preparation) was found at ratios of 0.5 g of C18/7 ml of IVIG and 0.22 g of dry SDR HyperD/7 ml of IVIG. Binding capacities of TnBP were greater than 140 mg/g of C18 and greater than 318 mg/g of dry SDR HyperD. Complete removal of Triton X-45 (<2 ppm) was obtained at ratios of 1g of C18/7 ml of IVIG and 0.44 g of dry SDR HyperD/7 ml of IVIG or above, corresponding to binding capacities in excess of 70 mg/g of C18 and in excess of 159 mg/g of dry SDR HyperD. Residual Triton X-100 was less than 30 ppm at a ratio of 4 g/14 ml of immunoglobulin G (IgG) for the C18 sorbent. Triton X-100 was less than 10 ppm when using SDR HyperD at a ratio of 0.66 g/7 ml of IgG, corresponding to a binding capacity of approximately 106 mg of Triton X-100/g of dry SDR HyperD. Good recoveries of IVIG were achieved in the effluent from both sorbents.

  5. Modeling glucose and free fatty acid kinetics during insulin-modified intravenous glucose tolerance test in healthy humans: role of counterregulatory response.

    PubMed

    Thomaseth, Karl; Brehm, Attila; Pavan, Alessandra; Pacini, Giovanni; Roden, Michael

    2014-08-01

    Insulin administration during insulin-modified intravenous glucose tolerance test (IM-IVGTT) can induce transient hypoglycemia in healthy insulin-sensitive subjects. This triggers counterregulatory reflex (CRR) responses, which influence the kinetics of glucose and nonesterified fatty acids (NEFA), and undermines the accuracy of mathematical modeling methods that do not explicitly account for CRR. The aim of this study is to evaluate mathematical models of glucose and NEFA kinetics against experimental data in the presence or absence of CRR. Thirteen healthy nondiabetic subjects underwent a standard IM-IVGTT and a modified test (GC-IM-IVGTT) with a variable glucose infusion preventing hypoglycemia. While model predictions fit very well with glucose and NEFA data from GC-IM-IVGTT, they lagged behind observations from IM-IVGTT during recovery from hypoglycemia, independently of insulinemia, which did not differ significantly between protocols. A modification to the glucose minimal model, using the glucose concentration below a threshold as a signal for CRR, improves model predictions for both glucose and NEFA. The associated increase in endogenous glucose production correlates, among various CRR hormones, mainly with the dynamics of glucagon concentration. The modified minimal models introduce new parameters that quantify strength and duration of CRR following hypoglycemia. Although CRR represents an unwanted side-effect in IM-IVGTT occurring only in insulin-sensitive subjects, this study provides new insights leading to improved procedures for estimating insulin sensitivity from IM-IVGTT, which may also allow for assessing the individual capacity of recovery from hypoglycemic events in patients treated with insulin or insulin-releasing drugs.

  6. Tumor tropism of intravenously injected human-induced pluripotent stem cell-derived neural stem cells and their gene therapy application in a metastatic breast cancer model.

    PubMed

    Yang, Jing; Lam, Dang Hoang; Goh, Sally Sallee; Lee, Esther Xingwei; Zhao, Ying; Tay, Felix Chang; Chen, Can; Du, Shouhui; Balasundaram, Ghayathri; Shahbazi, Mohammad; Tham, Chee Kian; Ng, Wai Hoe; Toh, Han Chong; Wang, Shu

    2012-05-01

    Human pluripotent stem cells can serve as an accessible and reliable source for the generation of functional human cells for medical therapies. In this study, we used a conventional lentiviral transduction method to derive human-induced pluripotent stem (iPS) cells from primary human fibroblasts and then generated neural stem cells (NSCs) from the iPS cells. Using a dual-color whole-body imaging technology, we demonstrated that after tail vein injection, these human NSCs displayed a robust migratory capacity outside the central nervous system in both immunodeficient and immunocompetent mice and homed in on established orthotopic 4T1 mouse mammary tumors. To investigate whether the iPS cell-derived NSCs can be used as a cellular delivery vehicle for cancer gene therapy, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected through tail vein into 4T1 tumor-bearing mice. The transduced NSCs were effective in inhibiting the growth of the orthotopic 4T1 breast tumor and the metastatic spread of the cancer cells in the presence of ganciclovir, leading to prolonged survival of the tumor-bearing mice. The use of iPS cell-derived NSCs for cancer gene therapy bypasses the sensitive ethical issue surrounding the use of cells derived from human fetal tissues or human embryonic stem cells. This approach may also help to overcome problems associated with allogeneic transplantation of other types of human NSCs.

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

    SciTech Connect

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

    1980-03-01

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

  8. Dexmedetomidine: clinical application as an adjunct for intravenous regional anesthesia.

    PubMed

    Ramadhyani, Usha; Park, Jason L; Carollo, Dominic S; Waterman, Ruth S; Nossaman, Bobby D

    2010-12-01

    The selective α-2 adrenoceptor agonist, dexmedetomidine, has been shown to be a useful, safe adjunct in perioperative medicine. Intravenous regional anesthesia is one of the simplest forms of regional anesthesia and has a high degree of success. However, intravenous regional anesthesia is limited by the development of tourniquet pain and its inability to provide postoperative analgesia. To improve block quality, prolong postdeflation analgesia, and decrease tourniquet pain, various chemical additives have been combined with local anesthetics, although with limited success. The antinociceptive effects of α-2 adrenoceptor agonists have been shown in animals and in humans. However, less is known about the clinical effects of dexmedetomidine when coadministered with local anesthetics in patients undergoing intravenous regional anesthesia. This review examines what is currently known to improve our understanding of the properties and application of dexmedetomidine when used as an adjunct in intravenous regional anesthesia.

  9. A liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of escin Ia and escin Ib in human plasma: application to a pharmacokinetic study after intravenous administration.

    PubMed

    Liu, Lidong; Wu, Xiujun; Wu, Dan; Wang, Yingwu; Li, Pengfei; Sun, Yantong; Yang, Yan; Gu, Jingkai; Cui, Yimin

    2010-12-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous quantification of escin Ia and escin Ib in human plasma. After a solid-phase extraction (SPE), the analytes were separated on a Zorbax Extend C(18) column by isocratic elution with a mobile phase of methanol-acetonitrile-10 mm ammonium acetate (27:27:46, v/v/v) at a flow rate of 1.0 mL/min and analyzed by mass spectrometry in the positive ion multiple reaction monitoring mode. The precursor to product ion transitions of m/z 1131.8 → 807.6 was used to quantify escin Ia and escin Ib. Good linearity was achieved over a wide range of 2.00-900 ng/mL for escin Ia and 1.50-662 ng/mL for escin Ib. The intra- and inter-day precisions (as relative standard deviation) were less than 11% for each QC level of escin Ia and escin Ib. The accuracies (as relative error) were within ±5.27% for escin Ia and within ±4.07% for escin Ib. The method was successfully employed in a pharmacokinetic study after a single intravenous infusion administration of sodium aescinate injection containing 10 mg escin to each of the 10 healthy volunteers.

  10. [Complications caused by intravenous therapy].

    PubMed

    Quirós Luque, José María; Gago Fornells, Manuel

    2005-11-01

    Nursing professionals must know everything related to complications caused by intravenous therapy including the ways to prevent and solve these complications. We need not forget that nurses are the ones mainly responsible for the insertion, manipulation, removal and care of catheters.

  11. [Lethal intravenous injection of benzine].

    PubMed

    Zirwes, Christian; Ritz-Timme, Stefanie; Hinsch, Nora; Kardel, Bernd; Hartung, Benno

    2015-01-01

    A man who suffered from chronic pain syndrome died two days after intravenous injection of 2 ml benzine. Previous suicide attempts by drug intoxication and strangulation had failed. Death occurred due to multi-organ failure. We present the results of the clinical, morphological and toxicological examinations performed.

  12. IgM-Enriched Human Intravenous Immunoglobulin-Based Treatment of Patients With Early Donor Specific Anti-HLA Antibodies After Lung Transplantation

    PubMed Central

    Ius, Fabio; Sommer, Wiebke; Kieneke, Daniela; Tudorache, Igor; Kühn, Christian; Avsar, Murat; Siemeni, Thierry; Salman, Jawad; Erdfelder, Carolin; Verboom, Murielle; Kielstein, Jan; Tecklenburg, Andreas; Greer, Mark; Hallensleben, Michael; Blasczyk, Rainer; Schwerk, Nicolaus; Gottlieb, Jens; Welte, Tobias; Haverich, Axel; Warnecke, Gregor

    2016-01-01

    Background At our institution, until April 2013, patients who showed early donor specific anti-HLA antibodies (DSA) after lung transplantation were preemptively treated with therapeutic plasma exchange (tPE) and a single dose of Rituximab. In April 2013, we moved to a therapy based on IgM-enriched human immunoglobulins (IVIG), repeated every 4 weeks, and a single dose of Rituximab. Methods This observational study was designed to evaluate the short-term patient and graft survival in patients who underwent IVIG-based DSA treatment (group A, n = 57) versus contemporary patients transplanted between April 2013 and January 2015 without DSA (group C, n = 180), as well as to evaluate DSA clearance in IVIG-treated patients versus historic patients who had undergone tPE-based treatment (group B, n = 56). Patient records were retrospectively reviewed. Follow-up ended on April 1, 2015. Results At 6 months and 1 year of follow-up, group A had a survival similar to group C (P = 0.81) but better than group B (P = 0.008). Group A showed statistically nonsignificant trends toward improved freedom from pulsed-steroid therapy and biopsy-confirmed rejection over groups B and C. The DSA clearance was better in group A than group B at treatment end (92% vs 64%; P = 0.002) and last DSA control (90% vs 75%; P = 0.04). Conclusions Patients with new early DSA but without graft dysfunction that are treated with IVIG and Rituximab have similarly good early survival as contemporary lung transplant recipients without early DSA. The IVIG yielded increased DSA clearance compared with historic tPE-based treatment, yet spontaneous clearance of new DSA also remains common. PMID:26714123

  13. Intravenous catheter for intracorporeal plasma filtration.

    PubMed

    Handley, Harold H; Gorsuch, Rey; Levin, Nathan W; Ronco, Claudio

    2002-01-01

    Future advances in dialysis of end-stage renal disease patients may include improvements in therapeutic continuity and patient mobility. Continuous renal replacement therapies could lead to self-contained, mobile and potentially wearable dialysis units. We investigated an experimental, intravenous slow-continuous plasma separation system (IPSS) as a precursor to direct intravenous hemofiltration. An intracorporeal catheter employs asymmetric hollow fibers to separate blood cells from plasma in vivo. The fibers possess a sieving coefficient of 0.7 microm and remove 99.99% of all platelets. In vivo, catheters sustain an average plasma separation flow rate of 3 ml/min over 22 h, sufficient to remove 2 net liters of water from pigs through an extracorporeal hemofilter. Used catheter fibers are relatively free of protein deposition or clots in situ. In vitro studies suggest that human catheters may perform at 3-4 times the rate of porcine catheters. IPSS is proposed for acute fluid removal in CHF patients refractory to diuretics.

  14. Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

    PubMed Central

    Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

    2012-01-01

    BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

  15. Intravenous Solutions for Exploration Missions

    NASA Technical Reports Server (NTRS)

    Miller, Fletcher J.; Niederhaus, Charles; Barlow, Karen; Griffin, DeVon

    2007-01-01

    This paper describes the intravenous (IV) fluids requirements being developed for medical care during NASA s future exploration class missions. Previous research on IV solution generation and mixing in space is summarized. The current exploration baseline mission profiles are introduced, potential medical conditions described and evaluated for fluidic needs, and operational issues assessed. We briefly introduce potential methods for generating IV fluids in microgravity. Conclusions on the recommended fluid volume requirements are presented.

  16. Intravenous nutrition during a twin pregnancy.

    PubMed

    Karamatsu, J T; Boyd, A T; Cooke, J; Vinall, P S; McMahon, M J

    1987-01-01

    A case is reported of a woman in the third trimester of a twin pregnancy who required intravenous nutrition because of inadequate absorption of nutrients due to a jejunoileal bypass. Weight gain was poor, and there was evidence of intrauterine growth retardation before commencement of intravenous feeding. She received overnight intravenous nutrition for 6 weeks and gained weight with ultrasound evidence of fetal growth. During the 33rd week of gestation, she was delivered of healthy twin males who were at appropriate birth weights and development for their age of gestation. The considerations in intravenous nutrition for a twin pregnancy after jejunoileal bypass are discussed.

  17. Descending polyneuropathy in an intravenous drug user.

    PubMed

    O'Sullivan, Jean M; McMahon, Geraldine

    2005-10-01

    A 27-year-old male intravenous drug user presented to the Emergency Department of St James's Hospital with a 1-week history of progressive dysphasia, dysphagia and difficulty 'holding his head up' and 'keeping his eyes open'. He also complained of increasing weakness in his upper limbs, as a result of which he kept dropping things. He was on a methadone program but was using both intravenous heroin and cocaine at the time of presentation. Examination of his motor function revealed generalized hypotonia, hyporeflexia and reduced power in both upper limbs. No sensory loss was observed. Co-ordination was intact. The clinical picture of a proximal symmetrical descending weakness and an absence of sensory loss was suggestive of botulism. Clostridium botulinum is a spore-forming, obligate anaerobe. The three forms of human botulism are food-borne, wound and intestinal. A fourth man-made form is produced from aerosolized botulinum toxin and results in inhalational botulism. A little as 1 g of aerosolized botulinum toxin has the potential to kill 1.5 million people. Toxin is detected in serum or stool specimens in only approximately 46% of clinically diagnosed cases. Treatment involves supportive care and early passive immunization with equine antitoxin. Patients should be regularly assessed for loss of gag and cough reflex, control of oropharyngeal secretions, oxygen saturation, vital capacity and inspiratory force. When respiratory function begins to deteriorate, anticipatory intubation is indicated. Early symptom recognition and early treatment with antitoxin are essential in order to prevent mortality, and to prevent additional cases, it is important to ascertain the presence of similar symptoms in contacts of the patient and local public health officials must be notified as one case may herald an outbreak. Given the continued threat of bioterrorism, the Centre for Disease Control Surveillance System in the United States must also be notified of any cases of botulism.

  18. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty

    PubMed Central

    Golpanian, Samuel; DiFede, Darcy L.; Pujol, Marietsy V.; Lowery, Maureen H.; Levis-Dusseau, Silvina; Goldstein, Bradley J.; Schulman, Ivonne H.; Longsomboon, Bangon; Wolf, Ariel; Khan, Aisha; Heldman, Alan W.; Goldschmidt-Clermont, Pascal J.; Hare, Joshua M.

    2016-01-01

    Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty. PMID:26933813

  19. A prototype space flight intravenous injection system

    NASA Technical Reports Server (NTRS)

    Colombo, G. V.

    1985-01-01

    Medical emergencies, especially those resulting from accidents, frequently require the administration of intravenous fluids to replace lost body liquids. The development of a prototype space flight intravenous injection system is presented. The definition of requirements, injectable concentrates development, water polisher, reconstitution hardware development, administration hardware development, and prototype fabrication and testing are discussed.

  20. Partial intravenous anesthesia in cats and dogs.

    PubMed

    Duke, Tanya

    2013-03-01

    The partial intravenous anesthesia technique (PIVA) is used to lower the inspired concentration of an inhalational anesthetic by concurrent use of injectable drugs. This technique reduces the incidence of undesirable side-effects and provides superior quality of anesthesia and analgesia. Drugs commonly used for PIVA include opioids, alpha-2 adrenergic agonists, injectable anesthetic agents, and lidocaine. Most are administered by intravenous infusion.

  1. Cannabis in the arm: what can we learn from intravenous cannabinoid studies?

    PubMed

    Englund, Amir; Stone, James M; Morrison, Paul D

    2012-01-01

    Cannabis is widely used recreationally and for symptomatic relief in a number of ailments. However, cannabis has been implicated as a risk factor for the development of psychotic illness. For forty years researchers have utilised intravenous preparations of Δ(9)-THC, as well as several other phytocannabinoids, in a laboratory setting. The intravenous route has the most reliable pharmacokinetics, reducing inter-individual variation in bioavailability and is well suited for the delivery of synthetic compounds containing a sole pharmacological moiety. Given the association between cannabinoids and psychotic illness, there has been a resurgence of interest in experimental studies of cannabinoids in humans, and the intravenous route has been employed. Here in a critical review, we appraise the major findings from recent intravenous cannabinoid studies in humans and trace the historical roots of this work back to the 1970's.

  2. Use and abuse of intravenous solutions.

    PubMed

    Vidt, D G

    1975-05-05

    Recent microbial infusion disasters underline the fact that infusions carry a substantial risk of morbidity and mortality. Those who make a habit of setting up an intravenous infusion as a convenient route for the administration of drugs, or just in case it may be needed later, would do well to review their methodsmthe increased probability of contamination and subsequent patient infection by the practice of adding drugs to intravenous fluids is not generally recognized. To reduce the possibility of microbial contamination, the open system with tube containers should be opened only in an aseptic environment, eg, a laminar flow hood, to allow the vacuum to be replace by aseptic air; the open-system containers should be opened only in an aseptic environment, and a bacterial filter should be inserted in the air entry port of the closure. Routine monitoring of intravenous solutions for microbial contamination should be standard procedure for any institution providing intravenous fluid therapy to patientsmthe following recommendations are suggested for consideration by hospital pharmacy and therapeutics committees: 1, The addition of drugs to intravenous fluids should be discouraged except in recognized cases of emergency. 2 when the addition of drugs to intravenous fluids is indicated, only one drug should be added to an intravenous fluid, and the only intravenous fluids used for this purpose should be isotonic saline or 5% dextrose solution in water. More complicated electrolyte solutions and protein hydrolysate solutions should never be used for additive purposes. Guidelines should be established in hospitals for the addition of drugs to intravenous fluids. These guidelines should be followed by trained personnel who have access to all available compatibility data. Additions should be made under aseptic conditions by trained personnel, preferably in the hospital pharmacy. 4. All additions of drugs should be included in the patient's permanent drug file, and the

  3. Optical detection of intravenous infiltration

    NASA Astrophysics Data System (ADS)

    Winchester, Leonard W.; Chou, Nee-Yin

    2006-02-01

    Infiltration of medications during infusion therapy results in complications ranging from erythema and pain to tissue necrosis requiring amputation. Infiltration occurs from improper insertion of the cannula, separation of the cannula from the vein, penetration of the vein by the cannula during movement, and response of the vein to the medication. At present, visual inspection by the clinical staff is the primary means for detecting intravenous (IV) infiltration. An optical sensor was developed to monitor the needle insertion site for signs of IV infiltration. Initial studies on simulated and induced infiltrations on a swine model validated the feasibility of the methodology. The presence of IV infiltration was confirmed by visual inspection of the infusion site and/or absence of blood return in the IV line. Potential sources of error due to illumination changes, motion artifacts, and edema were also investigated. A comparison of the performance of the optical device and blinded expert observers showed that the optical sensor has higher sensitivity and specificity, and shorter detection time than the expert observers. An improved model of the infiltration monitoring device was developed and evaluated in a clinical study on induced infiltrations of healthy adult volunteers. The performance of the device was compared with the observation of a blinded expert observer. The results show that the rates of detection of infiltrations are 98% and 82% for the optical sensor and the observer, respectively. The sensitivity and specificity of the optical sensor are 0.97 and 0.98, respectively.

  4. Disposition of intravenous radioactive acyclovir

    SciTech Connect

    de Miranda, P.; Good, S.S.; Laskin, O.L.; Krasny, H.C.; Connor, J.D.; Lietman, P.S.

    1981-11-01

    The kinetic and metabolic disposition of (8-14C)acyclovir (ACV) was investigated in five subjects with advanced malignancy. The drug was administered by 1-hr intravenous infusion at doses of 0.5 and 2.5 mg/kg. Plasma and blood radioactivity-time, and plasma concentration-time data were defined by a two-compartment open kinetic model. There was nearly equivalent distribution of radioactivity in blood and plasma. The overall mean plasma half-life and total body clearance +/- SD of ACV were 2.1 +/- 0.5 hr and 297 +/- 53 ml/min/1.73 m2. Binding of ACV to plasma proteins was 15.4 +/- 4.4%. Most of the radioactive dose excreted was recovered in the urine (71% to 99%) with less than 2% excretion in the feces and only trace amounts in the expired Co2. Analyses by reverse-phase high-performance liquid chromatography indicated that 9-(carboxymethoxymethyl)guanine was the only significant urinary metabolite of ACV, accounting for 8.5% to 14.1% of the dose. A minor metabolite (less than 0.2% of dose) had the retention time of 8-hydroxy-9-((2-hydroxyethoxy)methyl)guanine. Unchanged urinary ACV ranged from 62% to 91% of the dose. There was no indication of ACV cleavage to guanine. Renal clearance of ACV was approximately three times the corresponding creatinine clearances.

  5. Intravenous, non-viral RNAi gene therapy of brain cancer.

    PubMed

    Pardridge, William M

    2004-07-01

    RNA interference (RNAi) has the potential to knock down oncogenes in cancer, including brain cancer. However, the therapeutic potential of RNAi will not be realised until the rate-limiting step of delivery is solved. The development of RNA-based therapeutics is not practical, due to the instability of RNA in vivo. However, plasmid DNA can be engineered to express short hairpin RNA (shRNA), similar to endogenous microRNAs. Intravenous, non-viral RNAi-based gene therapy is enabled with a new gene-targeting technology, which encapsulates the plasmid DNA inside receptor-specific pegylated immunoliposomes (PILs). The feasibility of this RNAi approach was evaluated by showing it was possible to achieve a 90% knockdown of brain tumour-specific gene expression with a single intravenous injection in adult rats or mice with intracranial brain cancer. The survival of mice with intracranial human brain cancer was extended by nearly 90% with weekly intravenous injections of PILs carrying plasmid DNA expressing a shRNA directed against the human epidermal growth factor receptor. RNAi-based gene therapy can be coupled with gene therapy that replaces mutated tumour suppressor genes to build a polygenic approach to the gene therapy of cancer.

  6. Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation

    PubMed Central

    Traeger, Lisa; Bäumer, Nicole; Schulze, Isabell; Kuhlmann, Tanja; Müller-Tidow, Carsten

    2016-01-01

    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. PMID:27404499

  7. Intravenous drug delivery in neonates: lessons learnt.

    PubMed

    Sherwin, Catherine M T; Medlicott, Natalie J; Reith, David M; Broadbent, Roland S

    2014-06-01

    Intravenous drug administration presents a series of challenges that relate to the pathophysiology of the neonate and intravenous infusion systems in neonates. These challenges arise from slow intravenous flow rates, small drug volume, dead space volume and limitations on the flush volume in neonates. While there is a reasonable understanding of newborn pharmacokinetics, an appreciation of the substantial delay and variability in the rate of drug delivery from the intravenous line is often lacking. This can lead to difficulties in accurately determining the pharmacokinetic and pharmacodynamic relationship of drugs in the smallest patients. The physical variables that affect the passage of drugs through neonatal lines need to be further explored in order to improve our understanding of their impact on the delivery of drugs by this route in neonates. Through careful investigation, the underlying causes of delayed drug delivery may be identified and administration protocols can then be modified to ensure predictable, appropriate drug input kinetics.

  8. Rational use of intravenous fat emulsions.

    PubMed

    Pelham, L D

    1981-02-01

    The composition, effect on blood components, relative value compared with intravenous dextrose, clinical applications as a caloric and fatty acid source, adverse reactions, limitations, and administration of intravenous fat emulsions are reviewed. Fat emulsions provide essential fatty acids and calories and are primarily used to supplement of parenteral nutrition regimens. Their use as a major source of calories remains limited because of cost. However, the trend toward aligning intravenous nutrition to that of the normal diet and the increased demand for peripherally administered parenteral nutrition have increased demand for use. The advantages and disadvantages presented may be used by clinicians to assist in establishing the role of intravenous fat therapy in nutritional support services.

  9. Reorganization for intravenous procedures in dentistry.

    PubMed

    Litchfield, N B

    1975-08-01

    The importance of reorganization for intravenous dental procedures, involving not only premises and equipment but also the dentist and his staff, is emphasised. These matters are discussed in detail with special emphasis on certain essential factors and psychologic aspects.

  10. Intravenous iron-containing products: EMA procrastination.

    PubMed

    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.

  11. Impaired splenic function and tuftsin deficiency in patients with intestinal failure on long term intravenous nutrition

    PubMed Central

    Zoli, G; Corazza, G; Wood, S; Bartoli, R; Gasbarrini, G; Farthing, M

    1998-01-01

    Background—Reticuloendothelial system function is impaired in humans receiving lipid regimens. 
Aims—To evaluate the effects of long term administration of long chain triglyceride emulsions on reticuloendothelial system function. 
Methods—Splenic function and tuftsin activity were measured in 20 patients on intravenous nutrition for intestinal failure, 20 patients with Crohn's disease who were not receiving intravenous nutrition, and 50 healthy controls. 
Results—Pitted red cells counts in patients on intravenous nutrition (8.0%) were significantly higher (p<0.001) than in healthy controls (0.6%) and in patients with Crohn's disease (0.9%). No difference was found between healthy controls and patients with Crohn's disease. There was a correlation (r=0.50; p<0.03) between percentage of pitted red cells and duration of intravenous nutrition. Tuftsin activity was significantly reduced in the intravenous nutrition patient group (6%) compared with both disease controls (16.5%, p<0.01) and healthy volunteers (17.8%, p<0.001) . An inverse correlation between tuftsin activity and pitted red cell percentage was found in the patients on intravenous nutrition (rs =−0.44, p<0.05). No relation was found in the patients on intravenous nutrition between pitted red cell percentage or tuftsin activity and type of disease, percentage of ideal body weight, residual length of small intestine, or administration (quantity and frequency) of lipid emulsion. Eight patients on intravenous nutrition had serious infections within the previous 12months. 
Conclusions—Patients with a short bowel treated with long term intravenous nutrition have impaired splenic function, reduced tuftsin activity, and an increased risk of infection. 

 Keywords: splenic function; hyposplenism; tuftsin; home parenteral nutrition; short bowel syndrome PMID:9824601

  12. Longer latency of sensory response to intravenous odor injection predicts olfactory neural disorder

    PubMed Central

    Kikuta, Shu; Matsumoto, Yu; Kuboki, Akihito; Nakayama, Tsuguhisa; Asaka, Daiya; Otori, Nobuyoshi; Kojima, Hiromi; Sakamoto, Takashi; Akinori, Kashio; Kanaya, Kaori; Ueha, Rumi; Kagoya, Ryoji; Nishijima, Hironobu; Toma-Hirano, Makiko; Kikkawa, Yayoi; Kondo, Kenji; Tsunoda, Koichi; Miyaji, Tempei; Yamaguchi, Takuhiro; Kataoka, Kazunori; Mori, Kensaku; Yamasoba, Tatsuya

    2016-01-01

    A near loss of smell may result from conductive and/or neural olfactory disorders. However, an olfactory test to selectively detect neural disorders has not been established. We investigated whether onset latency of sensory response to intravenous odor injection can detect neural disorders in humans and mice. We showed that longer preoperative onset latency of odor recognition to intravenous odor in patients with chronic rhinosinusitis predicted worse recovery of olfactory symptoms following sinus surgery. The onset latency of the olfactory sensory neuron (OSN) response to intravenous odor using synaptopHluorin signals from OSN axon terminals was delayed in mice with reduced numbers of OSNs (neural disorder) but not with increased mucus or blocked orthonasal pathways (conductive disorders). Moreover, the increase in onset latency correlated with the decrease in mature OSN numbers. Longer onset latency to intravenous odor injection is a useful biomarker for presence and severity of olfactory disorders with neural etiology. PMID:27734933

  13. A History of Intravenous Anesthesia in War (1656-1988).

    PubMed

    Roberts, Matthew; Jagdish, S

    2016-01-01

    The practice of anesthesia in war places significant restraints on the choice of anesthetic technique used; these include, but are not limited to, safety, simplicity, and portability. Ever since intravenous anesthesia became a practical alternative, there have been military doctors who felt that this technique was particularly suited to this environment. The challenge, as in civilian practice, has been to find the appropriate drugs as well as simple and safe delivery systems. The urgency of war has always stimulated innovation in medicine to counteract the ongoing development of weapons of war and their effects on the human body and to achieve improved survival as public expectations rise. This article traces the development of and the use of intravenous anesthesia by military physicians for battle casualties. The story starts long before the era of modern anesthesia, and the discussion concludes in the dog days of the cold war. The rapidly increasing interest in intravenous anesthesia in both civilian and military practice since the early 1990s is left for other authors to examine.

  14. Algorithms for intravenous insulin delivery.

    PubMed

    Braithwaite, Susan S; Clement, Stephen

    2008-08-01

    This review aims to classify algorithms for intravenous insulin infusion according to design. Essential input data include the current blood glucose (BG(current)), the previous blood glucose (BG(previous)), the test time of BG(current) (test time(current)), the test time of BG(previous) (test time(previous)), and the previous insulin infusion rate (IR(previous)). Output data consist of the next insulin infusion rate (IR(next)) and next test time. The classification differentiates between "IR" and "MR" algorithm types, both defined as a rule for assigning an insulin infusion rate (IR), having a glycemic target. Both types are capable of assigning the IR for the next iteration of the algorithm (IR(next)) as an increasing function of BG(current), IR(previous), and rate-of-change of BG with respect to time, each treated as an independent variable. Algorithms of the IR type directly seek to define IR(next) as an incremental adjustment to IR(previous). At test time(current), under an IR algorithm the differences in values of IR(next) that might be assigned depending upon the value of BG(current) are not necessarily continuously dependent upon, proportionate to, or commensurate with either the IR(previous) or the rate-of-change of BG. Algorithms of the MR type create a family of IR functions of BG differing according to maintenance rate (MR), each being an iso-MR curve. The change of IR(next) with respect to BG(current) is a strictly increasing function of MR. At test time(current), algorithms of the MR type use IR(previous) and the rate-of-change of BG to define the MR, multiplier, or column assignment, which will be used for patient assignment to the right iso-MR curve and as precedent for IR(next). Bolus insulin therapy is especially effective when used in proportion to carbohydrate load to cover anticipated incremental transitory enteral or parenteral carbohydrate exposure. Specific distinguishing algorithm design features and choice of parameters may be important to

  15. Measuring intravenous cannulation skills of practical nursing students using rubber mannequin intravenous training arms.

    PubMed

    Jones, Robert S; Simmons, Angela; Boykin, Gary L; Stamper, David; Thompson, Jennifer C

    2014-11-01

    This study examined the effectiveness of two training methods for peripheral intravenous (IV) cannulation; one using rubber mannequin IV training arms, and the other consisting of students performing the procedure on each other. Two hundred-sixty Phase II Army Practical Nursing students were randomized into two groups and trained to perform an IV cannulation procedure. All students watched a 12-minute training video covering standard IV placement procedures. Afterward, both groups practiced the procedure for an hour according to their assigned group. Students were then tested on IV placement in a live human arm using a 14-item testing instrument in three trials that were scored pass/fail. There was no difference in the groups' performance of the IV procedure on the first attempt: 51.7% (n = 92) of the human arm group passed the test, and 48.3% (n = 86) of the rubber mannequin group passed the test (p = 0.074). These data suggest that using rubber mannequin IV arms for IV skills training may be just as effective as training students using traditional methods. In addition, using simulation provides an extra benefit of reducing risks associated with learning the procedure on a fellow student.

  16. Mercury excretion and intravenous ascorbic acid.

    PubMed

    Dirks, M J; Davis, D R; Cheraskin, E; Jackson, J A

    1994-01-01

    We tested the hypothesis that intravenous ascorbic acid increases urinary excretion of mercury in subjects with low mercury levels from dental amalgam, food, and other sources. From 89 adult volunteers we selected 28 subjects with the highest mercury excretions (2 to 14 micrograms/24 h). We administered intravenous infusions of 500 ml lactated Ringer's solution with and without addition of 750 mg of ascorbic acid/kg body weight, up to 60 g ascorbic acid. Average mercury excretion during the 24 h after infusion of ascorbic acid was 4.0 +/- 0.5 micrograms (mean +/- SEM), which was not significantly more than after infusion of Ringer's solution alone (3.7 +/- 0.5 micrograms). Lead excretion was similarly unaffected. If ascorbic acid administered intravenously benefits some persons with suspected adverse reactions to mercury, the benefit in subjects similar to ours appears unrelated to short-term enhanced excretion of mercury or lead.

  17. Intravenous immunoglobulin therapy for antibody deficiency.

    PubMed Central

    Nolte, M T; Pirofsky, B; Gerritz, G A; Golding, B

    1979-01-01

    Twenty patients with antibody deficiency were treated at random with either intramuscular immune serum globulin (ISG) or intravenous modified immune serum globulin (M-ISG). Fourteen patients received of 259 M-ISG infusions during 242 months of treatment. Catastrophic vasomotor reactions were not observed. A single dose of 150 mg/kilo M-ISG increased serum IgG values a mean 248 mg%. Intravenous M-ISG therapy was effective in reducing the incidence of acute infections. Subjects receiving M-ISG developed 0.103 acute infections per month of treatment. Patients injected with ISG had 0.295 acute infections per month of treatment. Seven subjects had separate courses of both intravenous M-ISG and intramuscular ISG. Acute infections per month of treatment for M-ISG and ISG were 0.104 and 0.406, respectively. PMID:477026

  18. Promotion of gallbladder emptying by intravenous aminoacids.

    PubMed

    Zoli, G; Ballinger, A; Healy, J; O'Donnell, L J; Clark, M; Farthing, M J

    1993-05-15

    Patients receiving total intravenous nutrition have inert gallbladders; gallbladder sludge and gallstones often develop, but are preventable if gallbladder emptying can be improved. We measured the effect of giving rapid intravenous infusions of aminoacid solutions in eight normal subjects. Four regimens were tested (250 mL over 30 min, 250 mL over 10 min, 125 mL over 5 min, and 50 mL over 5 min). Gallbladder emptying, as measured by ultrasound and cholecystokinin release, depended on both the amount and the rate of aminoacid infusion. Rapid infusion of 125 mL of an aminoacid mixture (Synthamin 14 without electrolytes) over 5 min (2.1 g per min) produced a 64% reduction in gallbladder volume within 30 min, whereas a 50 mL infusion over 5 min produced only a 22% reduction. Intermittent rapid infusion of small amounts of aminoacids may prevent gallstones in patients receiving intravenous nutrition.

  19. Pulmonary edema induced by intravenous ethchlorvynol.

    PubMed

    Conces, D J; Kreipke, D L; Tarver, R D

    1986-11-01

    The intravenous injection of ethchlorvynol is an uncommon cause of noncardiac pulmonary edema. Two cases of intravenous ethchlorvynol-induced pulmonary edema are presented. The patients fell asleep after injecting the liquid contents of Placydil capsules (ethchlorvynol) and awoke several hours later with severe dyspnea. Arterial blood gases demonstrated marked hypoxia. Chest radiographs revealed bilateral diffuse alveolar densities. The patients' symptoms and radiographic findings resolved after several days of supportive care. Changes in the lung caused by ethchlorvynol may be the result of direct effect of the drug on the lung.

  20. Comparison study of intraosseous, central intravenous, and peripheral intravenous infusions of emergency drugs.

    PubMed

    Orlowski, J P; Porembka, D T; Gallagher, J M; Lockrem, J D; VanLente, F

    1990-01-01

    Intraosseous infusion of emergency drugs is a lifesaving alternative to intravenous administration when intravenous access cannot be rapidly established. We studied the comparative pharmacokinetics of the following six emergency drugs and solutions: epinephrine hydrochloride, 0.01 mg/kg; sodium bicarbonate, 1 mEq/kg; calcium chloride, 10 mg/kg; hydroxyethyl starch, 10 mL/kg; 50% dextrose in water, 250 mg/kg; and lidocaine hydrochloride, 1 mg/kg. Studies were conducted in normotensive, anesthetized dogs, with three animals studied with each of the drugs or solutions and each animal being treated with all three routes of administration (central intravenous, peripheral intravenous, and intraosseous) in randomized sequence. The effects of epinephrine were also assessed in a shock model. The intraosseous route of administration was comparable with the central and peripheral intravenous routes for all of the emergency drugs and solutions studied, with equivalent magnitudes of peak effect or drug level and equal or longer durations of action. Time to placement of the intraosseous needle varied from 15 seconds to 5 minutes, with a mean of 60 seconds. Time to placement of the needle varies with the skill and experience of the individual. With experience, all individuals could place the intraosseous needle in 60 seconds or less. The intraosseous route is comparable in effect to the central and peripheral intravenous routes of drug administration for epinephrine, sodium bicarbonate, hydroxyethyl starch, calcium chloride, 50% dextrose in water, and lidocaine and is a clinically feasible alternative when intravenous access will be critically delayed.

  1. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins

    PubMed Central

    Mukerji, Shibani S.; Lam, Alice D.

    2016-01-01

    We report the case of a 68-year-old man from southeastern Massachusetts presenting with encephalitis due to eastern equine encephalitis (EEE) virus. Despite the high morbidity and mortality rate of EEE, the patient made a near complete recovery in the setting of receiving early intravenous immunoglobulins. PMID:26740855

  2. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins.

    PubMed

    Mukerji, Shibani S; Lam, Alice D; Wilson, Michael R

    2016-01-01

    We report the case of a 68-year-old man from southeastern Massachusetts presenting with encephalitis due to eastern equine encephalitis (EEE) virus. Despite the high morbidity and mortality rate of EEE, the patient made a near complete recovery in the setting of receiving early intravenous immunoglobulins.

  3. Health Instruction Packages: Venipuncture and Intravenous Therapy.

    ERIC Educational Resources Information Center

    Gray, P. Allen, Jr.; And Others

    Text, illustrations, and exercises are utilized in these five learning modules to instruct nursing students in techniques for initiating intravenous (I.V.) therapy. The first module, "Selection of a Venipuncture Site: Arm" by P. Allen Gray, Jr., describes the utilization of a tourniquet in locating filled veins in the arm. The second…

  4. Peripherally inserted central catheters. Intravenous Nurses Society.

    PubMed

    1997-01-01

    The Intravenous Nurses Society (INS) recognizes the need for uniform terminology for peripherally inserted central catheters (PICCs) to encourage standardization for indications, care, and maintenance strategies for these devices. It also recognizes the need for recommendations regarding the choice, use, management, and discontinuation of PICCs to promote positive patient outcomes and enhance patient comfort, safety, and satisfaction.

  5. Intravenous nursing services: strategies for success.

    PubMed

    Campbell, K

    1996-01-01

    The intent of this article is to provide intravenous nurses with options for marketing and promoting their IV teams in institutions to enhance viability of the team concept and promote quality nursing care for the consumer. The article supplies options for a business plan to present to administration to promote the team concept both in the hospital and in alternate site settings.

  6. Epileptic fits under intravenous midazolam sedation.

    PubMed

    Robb, N D

    1996-09-07

    A case is presented of a patient who suffered from recurrent epileptic fits while being treated under intravenous sedation with midazolam. Those using sedation are advised to beware of the patient who gives a history of fits being provoked in the dental environment.

  7. Oral triazolam pretreatment for intravenous sedation.

    PubMed Central

    Stopperich, P. S.; Moore, P. A.; Finder, R. L.; McGirl, B. E.; Weyant, R. J.

    1993-01-01

    This double-blind, controlled clinical trial assessed the anxiety relief provided by oral triazolam given before intravenous sedation. Twenty-two healthy adults undergoing third-molar surgery with intravenous sedation were enrolled in this study. Subjects were randomly assigned to receive either 0.25 mg of triazolam p.o. or an identically appearing placebo 45 to 60 min before venipuncture. Immediately before test drug administration, subjects completed the Corah Anxiety Scale, a Visual Analog Scale (VAS) assessing state anxiety, and the Interval Scale of Anxiety Response (ISAR). The VAS and ISAR were repeated immediately before venipuncture. Intravenous sedation medications consisted of fentanyl, midazolam, and methohexital. At 24 hr, assessments of the venipuncture and global experience were obtained. Results indicated that the characteristics of the triazolam and placebo patients were similar at baseline. With triazolam pretreatment, both the VAS and ISAR scores decreased significantly. Dose requirements for conscious sedation medications were decreased in the triazolam group. Patients rated the venipuncture experience significantly less unpleasant when pretreated with triazolam, and global ratings of the overall surgical experience favored triazolam. An oral-intravenous combination sedation technique using 0.25 mg of triazolam may have a significant therapeutic advantage for outpatient oral surgery. PMID:7943920

  8. Intravenous and subcutaneous immunoglobulin G replacement therapy.

    PubMed

    Bonilla, Francisco A

    2016-11-01

    Human polyclonal immunoglobulin G (IgG) for therapeutic use has been available for decades. This drug was developed for treatment of antibody deficiency (replacement therapy), although its use has expanded into many anti-inflammatory and immunomodulatory applications in recent years. This review focuses on IgG prescribing for replacement therapy. IgG for replacement is most often administered via the intravenous IgG (IVIG) or subcutaneous IgG (SCIG) routes. IVIG is usually administered every 34 weeks, and SCIG is usually administered weekly, although variations may be considered in all cases. Recently, a new product became available that uses hyaluronidase to facilitate absorption of large doses of SCIG less frequently (every 34 weeks, as with IVIG). There are important differences between the pharmacokinetics of these three routes of administration. IVIG therapy leads to high peaks and low troughs between infusions. IgG concentration fluctuates much less over time with SCIG. Hyaluronidase-facilitated SCIG is intermediate. SCIG may have lower bioavailability in comparison with IVIG and may require higher doses over time; this is not true for hyaluronidase SCIG. However, there are large variations in IgG half-life among individuals and with different products. Therefore, individualization of therapy is essential. Mild systemic flu-like adverse effects may affect up to 2025% of patients who receive IVIG, smaller fractions may experience more-severe symptoms, whereas anaphylaxis is exceedingly rare. General flu-like systemic adverse effects are minimal with SCIG (intermediate with hyaluronidase SCIG), but transient (24 hours), mild, local inflammatory symptoms at infusion sites are relatively common with both forms. Additional rare but important complications of IgG therapy include thrombotic events and hemolysis that can be seen at high doses with any route of administration. Renal adverse effects may occur with IVIG as well. The variety of IgG products and routes of

  9. First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas

    PubMed Central

    Patnaik, A.; Appleman, L. J.; Tolcher, A. W.; Papadopoulos, K. P.; Beeram, M.; Rasco, D. W.; Weiss, G. J.; Sachdev, J. C.; Chadha, M.; Fulk, M.; Ejadi, S.; Mountz, J. M.; Lotze, M. T.; Toledo, F. G. S.; Chu, E.; Jeffers, M.; Peña, C.; Xia, C.; Reif, S.; Genvresse, I.; Ramanathan, R. K.

    2016-01-01

    Background To evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of copanlisib, a phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). Patients and methods Phase I dose-escalation study including patients with advanced solid tumors or NHL, and a cohort of patients with type 2 diabetes mellitus. Patients received three weekly intravenous infusions of copanlisib per 28-day cycle over the dose range 0.1–1.2 mg/kg. Plasma copanlisib levels were analyzed for pharmacokinetics. Biomarker analysis included PIK3CA, KRAS, BRAF, and PTEN mutational status and PTEN immunohistochemistry. Whole-body [18F]-fluorodeoxyglucose positron emission tomography (18FDG-PET) was carried out at baseline and following the first dose to assess early pharmacodynamic effects. Plasma glucose and insulin levels were evaluated serially. Results Fifty-seven patients received treatment. The MTD was 0.8 mg/kg copanlisib. The most frequent treatment-related adverse events were nausea and transient hyperglycemia. Copanlisib exposure was dose-proportional with no accumulation; peak exposure positively correlated with transient hyperglycemia post-infusion. Sixteen of 20 patients treated at the MTD had reduced 18FDG-PET uptake; 7 (33%) had a reduction >25%. One patient achieved a complete response (CR; endometrial carcinoma exhibiting both PIK3CA and PTEN mutations and complete PTEN loss) and two had a partial response (PR; both metastatic breast cancer). Among the nine NHL patients, all six with follicular lymphoma (FL) responded (one CR and five PRs) and one patient with diffuse large B-cell lymphoma had a PR by investigator assessment; two patients with FL who achieved CR (per post hoc independent radiologic review) were on treatment >3 years. Conclusion Copanlisib, dosed intermittently on days 1, 8, and 15 of a 28-day cycle, was well tolerated and the MTD was determined to be 0.8 mg/kg. Copanlisib

  10. Hydrothorax, hydromediastinum and pericardial effusion: a complication of intravenous alimentation.

    PubMed

    Damtew, B; Lewandowski, B

    1984-06-15

    Complications secondary to intravenous alimentation are rare but potentially lethal. Massive bilateral pleural effusions and a pericardial effusion developed in a patient receiving prolonged intravenous alimentation. Severe respiratory distress and renal failure ensued. He recovered with appropriate treatment.

  11. Incarcerated intravenous heroin users: predictors of post-release utilization of methadone maintenance treatment.

    PubMed

    Lin, Huang-Chi; Wang, Peng-Wei; Yang, Yi-Hsin; Tsai, Jih-Jin; Yen, Cheng-Fang

    2016-01-01

    Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p < .001) and had ever received methadone maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p < .01) were more likely to enter methadone maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may

  12. Pharmacokinetic profile of cocaine following intravenous administration in the female rabbit

    PubMed Central

    Parlaman, Joshua P.; Thompson, Barbara L.; Levitt, Pat; Stanwood, Gregg D.

    2007-01-01

    Prenatal cocaine exposure in a rabbit intravenous model has revealed selective disruption of brain development and pharmacological responsiveness. We therefore examined the pharmacokinetic properties of cocaine in this model. Dutch-belted rabbits were surgically implanted with a catheter in the carotid artery, allowed to recover, and then injected intravenously with a cocaine bolus. Cocaine and benzoylecgonine concentrations were measured in arterial blood plasma and analyzed by nonlinear regression and noncompartmental analyses. Peak cocaine concentration occurred by 30s, was transient, and distribution was rapid. The profile of cocaine in the rabbit is similar to that observed in humans using cocaine at recreational doses. PMID:17383635

  13. Clinical applications of intravenous lipid emulsion therapy.

    PubMed

    Muller, Sam H; Diaz, James H; Kaye, Alan David

    2015-12-01

    Intravenous lipid emulsion (ILE; Intralipid) therapy, a standard treatment in local anesthetic toxicity, has demonstrated therapeutic efficacies for a number of different drug class-mediated toxicities. Some of these varied drug groups include antipsychotics, antidepressants, antiarrhythmics, and calcium channel blockers. To meet the objective of describing the growing number of indications for Intralipid therapy and any diverse effects and/or failures of Intralipid therapy in reversing multiple drug toxicities, we queried several Internet search engines with the key words "intravenous lipid emulsion therapy," "Intralipid," "lipid emulsion," and "local anesthetic systemic toxicity," resulting in the identification of 31 case reports for descriptive analysis. These case reports included 49 separate drug overdose cases involving ten separate drug classes which were successfully reversed with Intralipid. The education of clinicians regarding the beneficial and varied roles of Intralipid therapy in different clinical settings is warranted, particularly in terms of the potential for Intralipid therapy to reverse the toxicities of non-local anesthetic drugs.

  14. Visualization of Coronary Arteries from Intravenous Angiograms

    NASA Technical Reports Server (NTRS)

    Selzer, Robert H.

    1985-01-01

    Under most circumstances, the coronary arteries are not satisfactorily visualized in intravenous angiograms. The objective of this study is to develop computer image enhancement methods that will improve the quality of the latent coronary images to a degree sufficient to detect an obstructive lesion. Such a technique, if successful, could be used as a first step alternative to conventional coronary angiography for individuals with ambiguous noninvasive cardiac tests. The determination of no lesion from the intravenous procedure would relieve the need for the conventional angiogram, while verification of an obstructive lesion could be followed by a conventional angiogram. The nature of the imaging problem and a description of the methods and initial processing results are described in this paper.

  15. Hypophosphataemia and phosphorus requirements during intravenous nutrition.

    PubMed Central

    Tovey, S. J.; Benton, K. G.; Lee, H. A.

    1977-01-01

    Seven patients with acute illnesses developed hypophosphataemia whilst receiving intravenous nutrition which included a fat emulsion, Intralipid, a possible source of phosphorus. The authors' observations cast doubt on the bio-availability of the phosphorus contained in the phospholipid content of the fat emulsion. The currently recommended allowance of phosphorus for this type of patient appears to be too low and it is suggested that 0-5-0-75 mmol/kg body weight be provided, preferably as a neutral phosphate solution. Sine hypophosphataemia can occur at various time intervals after starting intravenous nutrition and precede clinical sequelae it is recommended that routine serum phosphate measurements are made in all patients receiving this treatment. PMID:407558

  16. Bacillus cereus panophthalmitis after intravenous heroin.

    PubMed

    Hatem, G; Merritt, J C; Cowan, C L

    1979-03-01

    Two healthy young black men developed panophthalmitis after intravenous heroin injections. Bacillus cereus, considered to be a relatively noncommon pathogen for man, was found to be the causative agent as it was recovered from the anterior chamber and viterous cavity of both cases. The ocular findings were unilateral in each case, and neither patient had any sistemic involvement from the bacteremia. The onset of visual symptoms varied from 24 to 36 hours after the last intravenous injection with the eye becoming rapidly blind. Photographs of the early fundus lesions included preretinal hypopyon-like lesions and peculiar changes in the blood vasculature. Intracameral gentamicin and steroids did not alter the cause, and treatment was enucleation.

  17. Diurnal Variation in Response to Intravenous Glucose*

    PubMed Central

    Whichelow, Margaret J.; Sturge, R. A.; Keen, H.; Jarrett, R. J.; Stimmler, L.; Grainger, Susan

    1974-01-01

    Intravenous glucose tolerance tests (25 g) were performed in the morning and afternoon on 13 apparently normal persons. The individual K values (rate of decline of blood sugar) were all higher in the morning tests, and the mean values were significantly higher in the morning. Fasting blood sugar levels were slightly lower in the afternoon. There was no difference between the fasting morning and afternoon plasma insulin levels, but the levels after glucose were lower in the afternoon. Growth hormone levels were low at all times in non-apprehensive subjects and unaffected by glucose. The results suggest that the impaired afternoon intravenous glucose tolerance, like oral glucose tolerance, is associated with impaired insulin release and insulin resistance. PMID:4817160

  18. Safety and efficacy of phage therapy via the intravenous route.

    PubMed

    Speck, Peter; Smithyman, Anthony

    2016-02-01

    Increasing development of antimicrobial resistance is driving a resurgence in interest in phage therapy: the use of bacteriophages to treat bacterial infections. As the lytic action of bacteriophages is unaffected by the antibiotic resistance status of their bacterial target, it is thought that phage therapy may have considerable potential in the treatment of a wide range of topical and localized infections. As yet this interest has not extended to intravenous (IV) use, which is surprising given that the historical record shows that phages are likely to be safe and effective when delivered by this route. Starting almost 100 years ago, phages were administered intravenously in treatment of systemic infections including typhoid, and Staphylococcal bacteremia. There was extensive IV use of phages in the 1940s to treat typhoid, reportedly with outstanding efficacy and safety. The safety of IV phage administration is also underpinned by the detailed work of Ochs and colleagues in Seattle who have over four decades' experience with IV injection into human subjects of large doses of highly purified coliphage PhiX174. Though these subjects included a large number of immune-deficient children, no serious side effects were observed over this extended time period. The large and continuing global health problems of typhoid and Staphylococcus aureus are exacerbated by the increasing antibiotic resistance of these pathogens. We contend that these infections are excellent candidates for use of IV phage therapy.

  19. Intravenous access: a comparison of two methods.

    PubMed

    Duffy, B L; Lee, J S

    1983-05-01

    The reliability in providing a continued venous route to the circulation is compared between a winged needle (Abbott "Butterfly--23 INT") and a plastic catheter (Jelco Teflon "Catheter Placement Unit", 22 gauge). The catheter remained within the vein in all cases and had a much lower incidence of total obstruction during the study period. Where an intravenous infusion is not in place, a plastic catheter provides a more reliable access route to the circulation than does a winged needle.

  20. Juvenile dermatomyositis: treatment with intravenous gammaglobulin.

    PubMed

    Collet, E; Dalac, S; Maerens, B; Courtois, J M; Izac, M; Lambert, D

    1994-02-01

    High-dose intravenous gammaglobulin (IVGG) has proved to be effective in the treatment of a number of immune disorders. We report two patients with juvenile dermatomyositis (DM) who improved with IVGG therapy. These patients had become refractory to corticosteroids and had developed unacceptable steroid toxicity. We suggest that IVGG can be useful in the treatment of juvenile DM, by reducing steroid requirements, and replacing immunosuppressive drugs.

  1. Synthetic Strategies for Engineering Intravenous Hemostats

    PubMed Central

    Chan, Leslie W.-G.; White, Nathan J.; Pun, Suzie H.

    2015-01-01

    While there are currently many well-established topical hemostatic agents for field administration, there are still limited tools to staunch bleeding at less accessible injury sites. Current clinical methods of restoring hemostasis after large volume blood loss include platelet and clotting factor transfusion, which have respective drawbacks of short shelf-life and risk of viral transmission. Therefore, synthetic hemostatic agents that can be delivered intravenously and encourage stable clot formation after localizing to sites of vascular injury are particularly appealing. In the past three decades, platelet substitutes have been prepared using drug delivery vehicles such as liposomes and PLGA nanoparticles that have been modified to mimic platelet properties. Additionally, structural considerations such as particle size, shape, and flexibility have been addressed in a number of reports. Since platelets are the first responders after vascular injury, platelet substitutes represent an important class of intravenous hemostats under development. More recently, materials affecting fibrin formation have been introduced to induce faster or more stable blood clot formation through fibrin crosslinking. Fibrin represents a major structural component in the final blood clot, and a fibrin-based hemostatic mechanism acting downstream of initial platelet plug formation may be a safer alternative to platelets to avoid undesired thrombotic activity. This review explores intravenous hemostats under development and strategies to optimize their clotting activity. PMID:25803791

  2. Synthetic Strategies for Engineering Intravenous Hemostats.

    PubMed

    Chan, Leslie W; White, Nathan J; Pun, Suzie H

    2015-07-15

    While there are currently many well-established topical hemostatic agents for field administration, there are still limited tools to staunch bleeding at less accessible injury sites. Current clinical methods to restore hemostasis after large volume blood loss include platelet and clotting factor transfusion, which have respective drawbacks of short shelf life and risk of viral transmission. Therefore, synthetic hemostatic agents that can be delivered intravenously and encourage stable clot formation after localizing to sites of vascular injury are particularly appealing. In the past three decades, platelet substitutes have been prepared using drug delivery vehicles such as liposomes and PLGA nanoparticles that have been modified to mimic platelet properties. Additionally, structural considerations such as particle size, shape, and flexibility have been addressed in a number of reports. Since platelets are the first responders after vascular injury, platelet substitutes represent an important class of intravenous hemostats under development. More recently, materials affecting fibrin formation have been introduced to induce faster or more stable blood clot formation through fibrin cross-linking. Fibrin represents a major structural component in the final blood clot, and a fibrin-based hemostatic mechanism acting downstream of initial platelet plug formation may be a safer alternative to platelets to avoid undesired thrombotic activity. This Review explores intravenous hemostats under development and strategies to optimize their clotting activity.

  3. COSMOS - a study comparing peripheral intravenous systems.

    PubMed

    López, Juan Luis González; Del Palacio, Encarnación Ferenández; Marti, Carmen Benedicto; Corral, Javier Olivares; Portal, Pilar Herrera; Vilela, Ana Arribi

    In many areas of the world, safety peripheral intravenous systems have come into widespread use. The Madrid region was the first in Spain to adopt such an approach. These systems, though initially introduced to protect users from sharps injuries, have now evolved to include patient protection features as well. Patient protection, simply stated, means closing the system to pathogen entry. The authors' purpose was to investigate, in a prospective and randomized study, the clinical performance of a closed safe intravenous system versus an open system (COSMOS - Compact Closed System versus Mounted Open System). COSMOS is designed to provide definitive answers, from a nursing perspective, to many topics related to peripheral venous catheterization, which have important implications in intravenous therapy and which have not been validated scientifically. Furthermore, it forms pioneering research in that it is the first clinical trial on medical devices in a legislated environment carried out entirely by nurses and whose promoter and principal investigator is a nurse. The objectives of COSMOS are to compare the effectiveness (as defined by time of survival without complications) and rates of catheter-related complications, such as phlebitis, pain, extravasation, blockage and catheter-related infections. It also looks at rates of catheter colonization, the ease of handling of both systems and overall costs. This article outlines the authors' approach, both in preparing hospital units for such an evaluation as well as in the choice of parameters and their method of study. Further articles will detail the results and findings of the study.

  4. Pharmocokinetics of hexobarbital in man after intravenous infusion.

    PubMed

    Breimer, D D; Honhoff, C; Zilly, W; Richter, E; van Rossum, J M

    1975-02-01

    The plasma levels of hexobarbital in humans were determined during and after a 30-min or 60-min zero-order intravenous infusion. Hexobarbital kinetics could be described by conceiving the body to exhibit two compartments. The plasma concentrations were fitted to the postinfusion equation and the parameters intrinsic to the two-compartment open model were estimated. The elimination half-life varied considerably among the 14 individuals (160-441-min), which could mainly be explained by the greatly varying metabolic clearance of the compound (123-360 ml/min). The apparent volume of distribution per kilogram of body weight was relatively constant (1.10 plus or minus 0.12 liters/kg).

  5. Control of light backscattering in blood during intravenous laser irradiation

    NASA Astrophysics Data System (ADS)

    Melnik, Ivan S.; Popov, V. D.; Rusina, Tatyana V.; Dets, Sergiy M.

    1997-02-01

    One of the most important problems in modern laser medicine is the determination of system response on laser treatment. Reaction of living system is significant during many kinds of laser procedures like surgery, therapy and biostimulation. Our study was aimed to optimize laser exposure using feed-back fiber system for intravenous laser irradiation of blood (ILIB). This system consisted of helium-neon laser (633 nm, 5 mW) with coupled fiber unit, photodetector and PC interface. Photodetector signals produced due to light backscattering were storaged and processed during all blood irradiation procedure. Significant time-dependent variations were observed within 9-15 min after beginning of treatment procedure and were correlated with number of trials, stage and character of disease. The designed feed-back system allows us to register a human blood response on laser irradiation to achieve better cure effect.

  6. Characterization of polymeric nanoparticles for intravenous delivery: Focus on stability.

    PubMed

    Oliveira, Claudia L; Veiga, Francisco; Varela, Carla; Roleira, Fernanda; Tavares, Elisiário; Silveira, Isabel; Ribeiro, Antonio J

    2017-02-01

    The nano-bio interaction has been of increased focus in the past years but very limited results have been obtained for polymeric nanoparticles (NP). Not only is needed to broaden the results obtained with model NP towards other nano-materials used for clinical application but the colloidal stability of NP as a variable consequence of the formation of the protein corona has been significantly understated. The lack and heterogeneity of assays to study NP stability and represent the biological environment call for the standardization of assays to improve the representativeness and comparability of results. In this paper, uncoated and PAH-coated PLGA NP have been prepared and characterized in regard to their potential for intravenous administration. The comparative study of the stability of NP in three media used to represent the biological environment-bovine serum albumin (BSA) solution, mouse and human plasma - revealed that both formulations were unstable in human plasma as opposed to the results obtained for other media. This unexpected behavior in plasmas of different origins could be correlated with a significant variation of the amount of proteins adsorbed to NP and, ultimately, with an approximately 6-fold difference in total protein concentration between the plasma samples. These results suggest that inter-species variation could impact on the colloidal stability of NP and enhance the need to understand the correlation between biological media and identify protocol-related interferences which, altogether, may evidence a relevant factor compromising in vitro- in vivo correlation and the translation of delivery systems aimed at intravenous administration.

  7. A Safety and Feasibility Study of an Allogeneic Colon Cancer Cell Vaccine Administered with a Granulocyte–Macrophage Colony Stimulating Factor–Producing Bystander Cell Line in Patients with Metastatic Colorectal Cancer

    PubMed Central

    Zheng, Lei; Edil, Barish H.; Soares, Kevin C.; El-Shami, Khaled; Uram, Jennifer N.; Judkins, Carol; Zhang, Zhe; Onners, Beth; Laheru, Daniel; Pardoll, Drew; Jaffee, Elizabeth M.; Schulick, Richard D.

    2014-01-01

    Background Despite recent advances in earlier detection and improvements in chemotherapy, the 5-year survival rate of patients with metastatic colorectal carcinoma remains poor. Immunotherapy is a potentially effective therapeutic approach to the treatment of colorectal carcinoma. Preclinical studies have supported the antitumor activity of immunization with a granulocyte–macrophage colony-stimulating factor (GM-CSF) producing murine colon tumor cell vaccine. Methods A novel colorectal cancer vaccine composed of irradiated, allogeneic human colon cancer cells and GM-CSF-producing bystander cells was developed and tested in combination with a single intravenous low dose of cyclophosphamide in a phase 1 study of patients with metastatic colorectal cancer. Results A total of nine patients were enrolled onto and treated in this study. Six patients had a history of colorectal adenocarcinoma hepatic metastases and underwent curative metastasectomy, while three other patients had unresectable stage IV disease. This study demonstrates the safety and feasibility of this vaccine administered in patients with metastatic colorectal cancer. At last follow-up, the six patients who underwent curative metastasectomy survived longer than 36 months, and four of these six patients were without disease recurrence. Immunologic correlate results suggest that the GM-CSF-producing colon cancer vaccine enhances the production of anti-MUC1 antibodies. Conclusions This vaccine is feasible and safe. Future investigation of the efficacy and antitumor immunity of this vaccine is warranted. PMID:24943235

  8. Intravenous infusions in chronic pain management.

    PubMed

    Kosharskyy, Boleslav; Almonte, Wilson; Shaparin, Naum; Pappagallo, Marco; Smith, Howard

    2013-01-01

    In the United States, millions of Americans are affected by chronic pain, which adds heavily to national rates of morbidity, mortality, and disability, with an ever-increasing prevalence. According to a 2011 report titled Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research by the Institute of Medicine of the National Academies, pain not only exacts its toll on people's lives but also on the economy with an estimated annual economic cost of at least $560 - 635 billion in health care costs and the cost of lost productivity attributed to chronic pain. Intravenous infusions of certain pharmacologic agents have been known to provide substantial pain relief in patients with various chronic painful conditions. Some of these infusions are better, and although not necessarily the first therapeutic choice, have been widely used and extensively studied. The others show promise, however are in need of further investigations. This article will focus on non-opiate intravenous infusions that have been utilized for chronic painful disorders such as fibromyalgia, neuropathic pain, phantom limb pain, post-herpetic neuralgia, complex regional pain syndromes (CRPS), diabetic neuropathy, and central pain related to stroke or spinal cord injuries. The management of patients with chronic pain conditions is challenging and continues to evolve as new treatment modalities are explored and tested. The following intravenous infusions used to treat the aforementioned chronic pain conditions will be reviewed: lidocaine, ketamine, phentolamine, dexmedetomidine, and bisphosphonates. This overview is intended to familiarize the practitioner with the variety of infusions for patients with chronic pain. It will not, however, be able to provide guidelines for their use due to the lack of sufficient evidence.

  9. Advances in Pediatric Intravenous Iron Therapy.

    PubMed

    Mantadakis, Elpis

    2016-01-01

    Iron deficiency anemia (IDA) continues to be very common worldwide. Intravenous (IV) iron is an infrequently used therapeutic option in children with IDA despite numerous studies in adults and several small but notable pediatric studies showing efficacy and safety. Presently, the availability of newer IV iron products allows for replacement of the total iron deficit at a single setting. These products appear safer compared to the high molecular weight iron dextrans of the past. Herein, we review the medical literature and suggest that front line use of IV iron should be strongly considered in diseases associated with IDA in children.

  10. Review of Intravenous Lipid Emulsion Therapy

    PubMed Central

    2016-01-01

    Intravenous fat emulsion (IVFE) is an important source of calories and essential fatty acids for patients receiving parenteral nutrition (PN). Administered as an individual infusion or combined with PN, the fats provided by IVFE are vital for cellular structural function and metabolism. The affinity of some medications to lipids has led to the use of IVFE as a treatment for any lipophilic drug overdose. This article will explain the available formulations of IVFE, administration, and maintenance issues, as well as the risks and benefits for various applications. PMID:27828934

  11. Severe hypophosphataemia after intravenous iron administration

    PubMed Central

    Anand, Gurpreet; Schmid, Christoph

    2017-01-01

    Iron deficiency is common and can be effectively treated with parenteral iron infusion. We report a case of an iron-deficient and vitamin D-deficient woman who developed severe symptomatic hypophosphataemia following intravenous ferric carboxymaltose administration. We stress the need of increased awareness of this potential complication among physicians. Patients should be informed of this complication and instructed to report for follow-up if they experience new musculoskeletal symptoms or worsening of tiredness. As severe hypophosphataemia is usually symptomatic, we recommend screening symptomatic patients for this complication. Recognising and treating the possible exacerbating factors, especially vitamin D deficiency, might be a simple measure to mitigate this complication. PMID:28289000

  12. Intravenous immune globulin in chronic lymphocytic leukaemia.

    PubMed Central

    Gamm, H; Huber, C; Chapel, H; Lee, M; Ries, F; Dicato, M A

    1994-01-01

    The most common complication of chronic lymphocytic leukaemia (CLL) is infection, which occurs mainly in advanced stages of disease or in those patients with hypogammaglobulinaemia. Intravenous immune globulin (IVIG) has been shown to be a useful prophylactic therapy against infections in such patients. A randomized, double-blind study on 36 patients receiving either 500 mg/kg or 250 mg/kg IVIG every 4 weeks was undertaken to determine the dose regimen required. There was no significant difference in the two treatment groups and we found that CLL patients were equally protected with low-dose IVIG. PMID:8033428

  13. Wireless application in intravenous infiltration detection system.

    PubMed

    Alley, Matthew S; Naramore, William J; Chou, Nee-Yin; Winchester, Leonard W

    2008-01-01

    The IrDA wireless protocol has been applied to a fiber optics based point-of-care system for the detection of intravenous infiltration. The system is used for monitoring patients under infusion therapy. It is optimized for portability by incorporating a battery source and wireless communication. The IrDA protocol provides secure data communication between the electronic module of the system and the PDAs carried by the nurses. The PDA is used for initiating the actions of the electronic module and for data transfer. Security is provided by specially designed software and hardware.

  14. [Ekbom syndrome in an intravenous methylphenidate abuser].

    PubMed

    Pereiro Gómez, César; Vicente-Alba, Javier; Ramos-Caneda, Alberto; Vázquez Ventoso, Carlos; Fontela-Vivanco, Eva; Díaz del Valle, Juan Carlos

    2012-01-01

    Ekbom syndrome is a mental disorder in which the patient has the monothematic delusion of being infected by parasites. It is an uncommon condition that was initially studied by dermatologists. The exactly etiology is unknown to date, though several causes have been proposed, including metabolic diseases (among other physical causes), psychiatric disorders, drugs, etc. Research has now found a relationship between drug abuse and psychotic symptoms, which appear to be due to altered levels of dopamine at the receptor level. In this article we review the clinical features of the condition and present the case report of an intravenous methylphenidate abuser who developed a delusion of parasitosis.

  15. Intravenous pamidronate in osteogenesis imperfecta type VII.

    PubMed

    Cheung, Moira S; Glorieux, Francis H; Rauch, Frank

    2009-03-01

    Cyclical intravenous treatment with pamidronate is widely used to treat osteogenesis imperfecta (OI) types I, III, and IV, which are due to dominant mutations affecting collagen type I alpha chains. There is no information about the effects of pamidronate in children with OI type VII, an autosomal-recessive form of OI caused by a mutation in the cartilage-associated protein gene. In this retrospective single-center study, we compared the effects of pamidronate in four girls with OI type VII (age range 3.9-12.7 years) to those in eight girls with OI types caused by collagen type I mutations who were matched for age and disease severity. During 3 years of pamidronate therapy, lumbar spine areal bone mineral density increased and lumbar vertebral bodies improved in shape in patients with OI type VII. Other outcomes such as fracture rates and mobility scores did not show statistically significant changes in this small study cohort. There were no significant side effects noted during the time of follow-up. Thus, intravenous treatment with pamidronate seems to be safe and of some benefit in patients with OI type VII.

  16. Intravenous desensitization to beta-lactam antibiotics.

    PubMed

    Borish, L; Tamir, R; Rosenwasser, L J

    1987-09-01

    Patients allergic to penicillin (PCN) often require treatment with beta-lactam antibiotics for life-threatening bacterial infections. In this article, we review our experience with rapid intravenous desensitization for patients who gave a history of PCN allergy and who had hypersensitivity demonstrated by skin tests. Skin testing was performed with both prick and intradermal techniques and with the recommended antibiotic as well as PCN G, penicilloyl polylysine, and a minor determinant mixture. Patients were transferred to the intensive care unit, and desensitization was performed with a buret technique that required minimal preparation and was easily applied to any antibiotic. Fifteen desensitizations in 12 patients were associated with no immediate reactions. One patient developed a delayed reaction consisting of a pruritic rash and angioedema. A second patient developed a more serious delayed serum sickness-like illness with fever, rash, eosinophilia, abnormal liver function tests, and urinary abnormalities. These reactions did not necessitate stopping the antibiotic, although the latter patient required corticosteroids to suppress his symptoms. Rapid intravenous desensitization is a rapid, safe, and effective technique for patients demonstrating hypersensitivity to beta-lactam antibiotics who require therapy with these medications.

  17. Panlobular emphysema in young intravenous Ritalin abusers

    SciTech Connect

    Schmidt, R.A.; Glenny, R.W.; Godwin, J.D.; Hampson, N.B.; Cantino, M.E.; Reichenbach, D.D. )

    1991-03-01

    We studied a distinctive group of young intravenous Ritalin abusers with profound obstructive lung disease. Clinically, they seemed to have severe emphysema, but the pathologic basis of their symptoms had not been investigated previously. Seven patients have died and been autopsied: in four, the lungs were fixed, inflated, dried, and examined in detail radiologically, grossly, microscopically, and by electron probe X-ray microanalysis. All seven patients had severe panlobular (panacinar) emphysema that tended to be more severe in the lower lung zones and that was associated with microscopic talc granulomas. Vascular involvement by talc granulomas was variable, but significant interstitial fibrosis was not present. Five patients were tested for alpha-1-antitrypsin deficiency and found to be normal, as were six similar living patients. These findings indicate that some intravenous drug abusers develop emphysema that clinically, radiologically, and pathologically resembles that caused by alpha-1-antitrypsin deficiency but which must have a different pathogenesis. Talc from the Ritalin tablets may be important, but the mechanism remains to be elucidated.

  18. Intravenous buprenorphine self-administration by detoxified heroin abusers.

    PubMed

    Comer, Sandra D; Collins, Eric D; Fischman, Marian W

    2002-04-01

    Several sources indicate that intravenously administered buprenorphine may have significant abuse liability in humans. The present study evaluated the reinforcing effects of intravenously administered buprenorphine (0, 2, and 8 mg) in detoxified heroin-dependent participants during a 7.5-week inpatient study. Participants (n = 6) were detoxified from heroin over a 1.5-week period immediately after admission. Testing subsequently occurred in three 2-week blocks. During the first week of each 2-week block, the reinforcing effects of buprenorphine were evaluated. Participants first received a dose of buprenorphine and $20 and then were given either the opportunity to self-administer the dose or $20 during choice sessions. During the second week of each 2-week block, the direct effects of heroin were measured to evaluate potential long-lasting antagonist effects of buprenorphine. Progressive ratio break-point values were significantly higher after 2 and 8 mg of buprenorphine compared with placebo. Correspondingly, several positive subjective ratings increased after administration of active buprenorphine relative to placebo. Although there were few differences in peak effects produced by 2 versus 8 mg of buprenorphine, the higher buprenorphine dose generally produced longer-lasting effects. Heroin also produced dose-related increases in several subjective effects. Peak ratings produced by heroin were generally higher than peak ratings produced by buprenorphine. There was little evidence of residual antagonism produced by buprenorphine. These results demonstrate that buprenorphine served as a reinforcer under these conditions, and that it may have abuse liability in nonopioid-dependent individuals who abuse heroin.

  19. INTRAVENOUS REGIONAL ANTIBIOTIC PERFUSION THERAPY AS AN ADJUNCTIVE TREATMENT FOR DIGITAL LESIONS IN SEABIRDS.

    PubMed

    Fiorello, Christine V

    2017-03-01

    Foot infections are a common problem among seabirds in wildlife rehabilitation. Pododermatitis and digital infections are often challenging to treat because of the presence of suboptimal substrates, abnormal weight-bearing due to injuries, and suboptimal nutritional or health status. Seabirds represent the majority of animals requiring rehabilitation after oil spills, and foot problems are a common reason for euthanasia among these birds. Antibiotic intravenous regional perfusion therapy is frequently used in humans and other species to treat infections of the distal extremities, but it has not been evaluated in seabirds. During the 2015 Refugio oil spill response, four birds with foot lesions (pododermatitis, osteomyelitis, or both) were treated with ampicillin/sulbactam administered intravenously to the affected limb(s) in addition to systemic antibiotics and anti-inflammatories. Three of the birds, all brown pelicans ( Pelecanus occidentalis ) recovered rapidly and were released. Two of these birds had acute pododermatitis and were treated once with intravenous regional perfusion. They were released approximately 3 wk after the perfusion therapy. The third pelican had osteomyelitis of a digit. It was treated twice with intravenous regional perfusion and was released about 1 mo after the initial perfusion therapy. The fourth bird, a Pacific loon ( Gavia pacifica ), was treated once with perfusion therapy but did not respond to treatment and was euthanatized. No serious adverse effects were observed. This technique should be explored further in avian species.

  20. AMS method validation for quantitation in pharmacokinetic studies with concomitant extravascular and intravenous administration.

    PubMed

    Lappin, Graham; Seymour, Mark; Young, Graeme; Higton, David; Hill, Howard M

    2011-02-01

    A technique has emerged in the past few years that has enabled a drug's intravenous pharmacokinetics to be readily obtained in humans without having to conduct extensive toxicology studies by this route of administration or expand protracted effort in formulation. The technique involves the intravenous administration of a low dose of (14)C-labelled drug (termed a tracer dose) concomitantly with a non-labelled extravascular dose given at therapeutically levels. Plasma samples collected over time are analysed to determine the total parent drug concentration by LC-MS (which essentially measures that arising from the oral dose) and by LC followed by accelerator mass spectrometry (AMS) to determine the (14)C-drug concentration (i.e., that arising from the intravenous dose). There are currently no published accounts of how the principles of bioanalytical validation might be applied to intravenous studies using AMS as an analytical technique. The authors describe the primary elements of AMS when used with LC separation and how this off-line technique differs from LC-MS. They then discuss how the principles of bioanalytical validation might be applied to determine selectivity, accuracy, precision and stability of methods involving LC followed by AMS analysis.

  1. Proteus endocarditis in an intravenous drug user.

    PubMed

    Goel, Rohan; Sekar, Baskar; Payne, Mark N

    2015-11-26

    Infective endocarditis (IE) is a life-threatening condition with adverse consequences and increased mortality, despite improvements in treatment options. Diagnosed patients usually require a prolonged course of antibiotics, with up to 40-50% requiring surgery during initial hospital admission. We report a case of a 42-year-old intravenous drug user who presented feeling generally unwell, with lethargy, rigours, confusion and a painful swollen right leg. He was subsequently diagnosed with Proteus mirabilis endocarditis (fulfilling modified Duke criteria for possible IE) and deep vein thrombosis (DVT). He was successfully treated with single antibiotic therapy without needing surgical intervention or requiring anticoagulation for his DVT. Proteus endocarditis is extremely uncommon, with a limited number of case reports available in the literature. This case illustrates how blood cultures are invaluable in the diagnosis of IE, especially that due to unusual microorganisms. Our case also highlights how single antibiotic therapy can be effective in treating Proteus endocarditis.

  2. Intravenous therapy: a guide to good practice.

    PubMed

    Scales, Katie

    This article provides an overview of the principles of good practice that underpin intravenous (IV) therapy. The indications for choosing the IV route and selecting an appropriate vascular access device (VAD) are explained. Common insertion sites for VAD placement and the care and management of VADs are reviewed. Infection control aspects of IV therapy are be highlighted, including the management of IV equipment and the importance of the nurse's role in the prevention of infection associated with IV therapy. Common complications of IV therapy are explained and strategies suggested for their prevention. The article addresses the issues associated with general IV therapy, it does not address specialist subjects such as parenteral nutrition, chemotherapy or blood transfusion.

  3. Intravenous dihydroergotamine therapy for pediatric abdominal migraines.

    PubMed

    Raina, Madiha; Chelimsky, Gisela; Chelimsky, Thomas

    2013-10-01

    Abdominal migraines present with debilitating symptoms in adolescence. At our institution, the gastroenterology, neurology, and autonomic departments collaborated in treating patients with such presentations. This case series describes 6 patients who were given intravenous dihydroergotamine (DHE) for presumed abdominal migraines. DHE was only used when other agents like amitriptyline, verapamil, topiramate, or depakote had proved ineffective. DHE was started at 0.5 mg dose and on average 7 to 9 mg were given on each hospitalization. Patient ages ranged from 13 to 19 years with the majority being female. One patient did not respond to treatment. One patient was admitted 4 times for symptoms of abdominal migraines resolving with DHE. The average time between symptom relapse was about 5 to 12 months. Five of our 6 patients responded to the infusion without significant side effects. Based on these case series, DHE may be a treatment option in children with intractable abdominal migraine.

  4. The future of intravenous iron in nephrology.

    PubMed

    Coyne, Daniel W

    2011-06-01

    Management of anaemia in chronic kidney disease (CKD) patients can be difficult and expensive. The recently completed Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), the largest double-blinded trial of erythropoiesis-stimulating agents (ESA) treatment in CKD to date, provides us with a wealth of new information on the natural history of anaemia in Stage 3 and 4 CKD and the risks and benefits of use of ESAs. This section will discuss some of the TREAT trial results in the context of other recent studies of ESAs and intravenous iron in CKD patients. It will also review applying those results when choosing anaemia goals for an individual, and determining if iron therapy might improve anaemia.

  5. Systematic review: intravenous Ibuprofen in preterm newborns.

    PubMed

    Aranda, J V; Thomas, Ronald

    2006-06-01

    Ibuprofen, a nonsteroidal antiinflammatory drug, widely used as antipyretic, antiinflammatory, and analgesic agent and for therapy of arthritis, exerts a dose-dependent constriction of the ductus arteriosus in newborn lambs. Two intravenous preparations, namely ibuprofen lysine and ibuprofen-THAM, have been studied in preterm newborns with patent ductus arteriosus. Clinical trials have compared IV ibuprofen to placebo, or to indomethacin. Pharmacodynamic effects of this drug before and after its administration have also been evaluated. Compared with placebo, IV ibuprofen effectively closed PDA with minimal effect on renal function. One study using intravenous ibuprofen-THAM showed decreased renal function and increased risk of NEC and PPHN. Compared with indomethacin, IV ibuprofen lysine exerted similar efficacy (75% to 93% closure). However, indomethacin increased abnormal renal function and decreased mesenteric and cerebral blood flow and bio-energetics. Two clinical trials showed that ibuprofen did not reduce the incidence of intraventricular hemorrhage compared with placebo. The drug has prolonged elimination (plasma half-life = ca 23 hours), suggesting that once daily dosing is appropriate. Dose finding studies indicate that a starting dose of 10 mg/kg followed by 5 mg/kg/d for 2 more days provides optimal efficacy with the least adverse effects. Neonatal data on ibuprofen and indomethacin indicate that, on the first day of life when IVH prevention is desired, indomethacin and not ibuprofen should be used since ibuprofen has no effect on IVH risk. On or after the second day of postnatal life, when early or therapeutic PDA closure is needed, ibuprofen and not indomethacin is probably the first choice due to its better adverse event profile.

  6. How to Keep an Infusion Log: Intravenous Immune Globulin (IVIG)

    MedlinePlus

    How to keep an INFUSION LOG Intravenous Immune Globulin (IVIG) How to keep an INFUSION LOG The Value of Keeping Records Excellence in health care ... keeping track of your Intravenous Immune Globulin (IVIG) infusions. Each of the manufacturers prepares IVIG in a ...

  7. Transition of Stable Pediatric Patients With Pulmonary Arterial Hypertension from Intravenous Epoprostenol to Intravenous Treprostinil

    PubMed Central

    Ivy, D. Dunbar; Claussen, Lori; Doran, Aimee

    2007-01-01

    Intravenous epoprostenol was the first agent approved by the United States Food and Drug Administration for the management of pulmonary arterial hypertension (PAH). However, epoprostenol therapy carries the risks of a short half-life (<6 minutes) and side effects, including jaw pain, flushing, and headache. Recently, intravenous treprostinil has been studied, primarily in adults with PAH, and found to provide effective therapy. The effects of continuous intravenous treprostinil were retrospectively evaluated in 13 children with stable PAH who had been treated with epoprostenol for >1 year. Children were transitioned in the hospital over 24 hours using a rapid or slow strategy. The children were a mean age of 11 years (range 3 to 17) and were transitioned to treprostinil from August 2004 to August 2005. The baseline 6-minute walking distance was on average 516 ± 115 m (n = 9) and did not change after transition. Patients were treated with treprostinil for 1.1 ± 0.5 years. There were 2 deaths, and 2 patients transitioned to other therapy. Seven patients experienced ≥1 central-line infection. Despite a higher dose of treprostinil, the side effects were subjectively diminished. In conclusion, treprostinil provides an alternative therapy in children with PAH, with fewer side effects. However, evaluation regarding rates of infection requires further exploration. PMID:17317374

  8. Preparation of a Homologous (Human) Intravenous Botulinal Immune Globulin.

    DTIC Science & Technology

    1983-05-01

    incurring the danger ent proteins in plasma in a manner that will yield of circulatory volume overload. t immunoglobulin product suitable for intrave...puncture device: Two years, provided labeLing recommends storage "a" no rarmer tha.n 30o C. (30" C., one year). "TIpbold Vacin

  9. Donepezil treatment and the subjective effects of intravenous cocaine in dependent individuals.

    PubMed

    Grasing, Kenneth; Mathur, Deepan; Newton, Thomas F; DeSouza, Cherilyn

    2010-02-01

    Acetylcholinesterase (AChE) inhibitors increase synaptic levels of acetylcholine (ACh) by inhibiting its breakdown. Donepezil is a reversible AChE inhibitor that is clinically available and relatively selective for inhibiting AChE but not other cholinesterases. Because AChE inhibitors have been shown to decrease the reinforcing effects of cocaine in animals, our hypothesis was that pretreatment with donepezil would attenuate the perceived value and other positive subjective effects of cocaine. We conducted a within-subject, double-blind, placebo-controlled, laboratory-based evaluation of the subjective effects produced by intravenous cocaine in human subjects receiving oral donepezil. Following three days of daily treatment with 5mg of donepezil or oral placebo, participants received intravenous placebo or cocaine (0.18 and 0.36 mg/kg). After a three-day washout period, participants were crossed over to the opposite oral treatment, which was followed by identical intravenous infusions. Donepezil was well-tolerated with only two drug-related adverse events reported that were mild and self-limiting. Treatment with donepezil increased ratings of 'any' and 'good' drug effect produced by low-dose cocaine, without modifying the response to high-dose cocaine. When collapsed across intravenous dose, treatment with donepezil decreased dysphoric effects and somatic symptoms, but did not modify the value of cocaine injections as determined by the Multiple Choice Questionnaire (MCQ). In summary, pretreatment with donepezil potentiated some measures for nonspecific and positive effects of low-dose cocaine. Across all intravenous treatments, participants receiving donepezil reported fewer somatic-dysphoric effects. Neither of these actions support the value of donepezil as a treatment for cocaine dependence.

  10. Multiple Intravenous Infusions Phase 1b

    PubMed Central

    Cassano-Piché, A; Fan, M; Sabovitch, S; Masino, C; Easty, AC

    2012-01-01

    Background Minimal research has been conducted into the potential patient safety issues related to administering multiple intravenous (IV) infusions to a single patient. Previous research has highlighted that there are a number of related safety risks. In Phase 1a of this study, an analysis of 2 national incident-reporting databases (Institute for Safe Medical Practices Canada and United States Food and Drug Administration MAUDE) found that a high percentage of incidents associated with the administration of multiple IV infusions resulted in patient harm. Objectives The primary objectives of Phase 1b of this study were to identify safety issues with the potential to cause patient harm stemming from the administration of multiple IV infusions; and to identify how nurses are being educated on key principles required to safely administer multiple IV infusions. Data Sources and Review Methods A field study was conducted at 12 hospital clinical units (sites) across Ontario, and telephone interviews were conducted with program coordinators or instructors from both the Ontario baccalaureate nursing degree programs and the Ontario postgraduate Critical Care Nursing Certificate programs. Data were analyzed using Rasmussen’s 1997 Risk Management Framework and a Health Care Failure Modes and Effects Analysis. Results Twenty-two primary patient safety issues were identified with the potential to directly cause patient harm. Seventeen of these (critical issues) were categorized into 6 themes. A cause-consequence tree was established to outline all possible contributing factors for each critical issue. Clinical recommendations were identified for immediate distribution to, and implementation by, Ontario hospitals. Future investigation efforts were planned for Phase 2 of the study. Limitations This exploratory field study identifies the potential for errors, but does not describe the direct observation of such errors, except in a few cases where errors were observed. Not all

  11. Pharmacokinetics of (14) C-ortho-phenylphenol following intravenous administration in pigs.

    PubMed

    Nixon, Emma; Brooks, James D; Routh, Patricia A; Chittenden, Jason T; Baynes, Ronald E

    2017-04-01

    Workers in the USA are exposed to industrial formulations, which may be toxic. These formulations often contain preservatives or biocides such as ortho-phenylphenol (OPP). There are limited data describing OPP following intravenous administration to assess truly the clearance of this chemical in humans and other species. In vivo experiments were conducted in pigs to determine related pharmacokinetic parameters. (14) C-OPP was administered as an intravenous bolus dose. Blood, feces, urine and tissue samples were collected for analysis by liquid scintillation. Data were analyzed using non-compartmental and compartmental pharmacokinetic model approaches. These data fitted a three-compartment model and showed that the half-life of (14) C-OPP following the intravenous bolus in pigs was 46.26 ± 10.01 h. The kidneys play a crucial role in clearance of (14) C-OPP with a large percentage of the dose being found in the urine (70.3 ± 6.9% dose). Comparisons with other species suggest that (14) C-OPP clearance in pigs (2.48 ml h(-1)  kg(-1) ) is less than that in humans (18.87 ml h(-1)  kg(-1) ) and rats (35.51 ml h(-1)  kg(-1) ). Copyright © 2016 John Wiley & Sons, Ltd.

  12. Intravenous lipid emulsion and dexmedetomidine for treatment of feline permethrin intoxication: a report from 4 cases

    PubMed Central

    Ceccherini, G.; Perondi, F.; Lippi, I.; Grazia, G.; Marchetti, V.

    2015-01-01

    Four cases of feline permethrin intoxication are described. The cause of intoxication is the application of canine permethrin spot-on product (Advantix®, Bayer) by the owners. Principal clinical guidelines recommends the use of anticonvulsant drugs to treat seizures or neurological symptoms after initial stabilization and dermal decontamination. The use of lipid emulsion had an increasing interest in the last decade for treatment of toxicosis caused by lipophylic drugs as reported in human and in veterinary medical practices. All cats presented in this study, were treated with intravenous lipid emulsion (ILE) at variable dosages, and dexmedetomidine was also administered by intravenous way. No adverse reaction such as thrombophlebitis, overload circulation or others was noticed during and after administration of ILE. Dexmedetomidine was proved to be helpful in tranquillizing the cats. All cats were discharged in good condition faster than other cases treated without their use. PMID:26623376

  13. Intravenous methamphetamine self-administration in rats: effects of intravenous or intraperitoneal MDMA co-administration.

    PubMed

    Clemens, Kelly J; Cornish, Jennifer L; Hunt, Glenn E; McGregor, Iain S

    2006-10-01

    The combined use of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') with methamphetamine (METH) by recreational drug users is of particular concern due to their similar pharmacological and toxic profiles. In the current study we sought to elucidate why combining these particular drugs is such a popular choice among party-drug users. This was investigated through characterisation of the possible interactive effects of MDMA on METH intravenous self-administration. The first experiment involved characterisation of the METH dose-response curve for intravenous self-administration. Male Hooded-Wistar rats were trained to self-administer intravenous METH (0.01-0.3 mg/kg/infusion) and an inverted-U dose-response curve was obtained. In Experiment 2, a second squad of rats self-administered 0.01, 0.03 or 0.1 mg/kg/infusion METH and had small amounts of MDMA (0.001-0.03 mg/kg) then introduced into the infusion solution. Addition of MDMA to the METH infusion solution resulted in a dose independent reduction in responding. In Experiment 3, a third squad of rats was treated 20 min pre-session with an intraperitoneal injection of saline, 1.25 or 2.5 mg/kg of MDMA or METH to evaluate whether the reduction in responding evident in Experiment 2 was due to an MDMA-induced decrease in locomotor activity. Pre-treatment with intraperitoneal MDMA or METH had no effect on METH self-administration nor activity. We hypothesise that the reduction in METH self-administration caused by MDMA may reflect inhibitory effects of MDMA-induced 5-HT release on dopaminergic mechanisms.

  14. Water Intoxication Following Low-Dose Intravenous Cyclophosphamide

    PubMed Central

    Koo, Tai Yeon; Bae, Sang-Cheol; Park, Joon Sung; Lee, Chang Hwa; Park, Moon Hyang; Kang, Chong Myung

    2007-01-01

    Cyclophosphamide is frequently used for the treatment of severe lupus nephritis, but is very rarely associated with dilutional hyponatremia. Recently we experienced a case of water intoxication following low-dose intravenous cyclophosphamide. Five hours after one dose of intravenous pulse cyclophosphamide 750 mg, the patient developed nausea, vomiting, and general weakness. Serum sodium concentration revealed 114 mEq/L and her hyponatremia was initially treated with hypertonic saline infusion. Then her serum sodium concentration rapidly recovered to normal with water restriction alone. During the course of intravenous pulse cyclophosphamide therapy, one must be aware of the possibility of significant water retention. PMID:24459501

  15. Water intoxication following low-dose intravenous cyclophosphamide.

    PubMed

    Koo, Tai Yeon; Bae, Sang-Cheol; Park, Joon Sung; Lee, Chang Hwa; Park, Moon Hyang; Kang, Chong Myung; Kim, Gheun-Ho

    2007-06-01

    Cyclophosphamide is frequently used for the treatment of severe lupus nephritis, but is very rarely associated with dilutional hyponatremia. Recently we experienced a case of water intoxication following low-dose intravenous cyclophosphamide. Five hours after one dose of intravenous pulse cyclophosphamide 750 mg, the patient developed nausea, vomiting, and general weakness. Serum sodium concentration revealed 114 mEq/L and her hyponatremia was initially treated with hypertonic saline infusion. Then her serum sodium concentration rapidly recovered to normal with water restriction alone. During the course of intravenous pulse cyclophosphamide therapy, one must be aware of the possibility of significant water retention.

  16. An unreported complication of intravenously administered ibuprofen: gastrointestinal bleeding.

    PubMed

    Sarici, S U; Dabak, O; Erdinc, K; Okutan, V; Lenk, M K

    2012-03-01

    Ibuprofen is used for the closure of ductus arteriosus either intravenously or enterally. Although intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, transient renal failure, oliguria, hyponatremia and thrombocytopenia are reported complications during or after ibuprofen treatment, gastrointestinal bleeding, to our knowledge, has not been reported previously. We herein report a premature newborn, in whom ibuprofen was used intravenously for the closure of ductus arteriosus and gastrointestinal bleeding developed as a complication, and aim to discuss this rare adverse effect. In conclusion, we emphasize the importance of close follow-up of premature newborns during intravenous ibuprofen treatment considering also the other rare systemic side effects reported in the literature.

  17. Benefits of establishing an intravenous team and the standardization of peripheral intravenous catheters.

    PubMed

    da Silva, Gislene Aparecida; Priebe, Sheila; Dias, Fábio Nunes

    2010-01-01

    The purpose of this study was to show the importance of a team dedicated to intravenous (IV) insertion and the standardization of peripheral IV catheters in reducing venipuncture attempts, reducing cases of phlebitis, and optimizing costs. The benefits achieved by the team were a decrease in venipuncture attempts, a decrease of phlebitis (from 0.47% to 0.35%), the optimization of the team's time, and a 29.47% reduction in the use of catheters. The study corroborates the IV team's importance in the process of managing nurses' workflow, since it provides important indicators for quality management.

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

    PubMed

    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

  19. Intravenous iron in inflammatory bowel disease.

    PubMed

    Muñoz, Manuel; Gómez-Ramírez, Susana; García-Erce, José Antonio

    2009-10-07

    The prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%). Both iron deficiency (ID) and anemia of chronic disease contribute most to the development of anemia in IBD. The prevalence of ID is even higher (45%). Anemia and ID negatively impact the patient's quality of life. Therefore, together with an adequate control of disease activity, iron replacement therapy should start as soon as anemia or ID is detected to attain a normal hemoglobin (Hb) and iron status. Many patients will respond to oral iron, but compliance may be poor, whereas intravenous (i.v.) compounds are safe, provide a faster Hb increase and iron store repletion, and presents a lower rate of treatment discontinuation. Absolute indications for i.v. iron treatment should include severe anemia, intolerance or inappropriate response to oral iron, severe intestinal disease activity, or use of an erythropoietic stimulating agent. Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses). After the initial resolution of anemia and the repletion of iron stores, the patient's hematological and iron parameters should be carefully and periodically monitored, and maintenance iron treatment should be provided as required. New i.v. preparations that allow for giving 1000-1500 mg in a single session, thus facilitating patient management, provide an excellent tool to prevent or treat anemia and ID in this patient population, which in turn avoids allogeneic blood transfusion and improves their quality of life.

  20. The complexity of prescribing intravenous lipid emulsions.

    PubMed

    Waitzberg, Dan Linetzky; Torrinhas, Raquel Susana

    2015-01-01

    Intravenous lipid emulsions (LEs) are relevant for patients receiving parenteral nutrition because they prevent the depletion of essential fatty acids (FAs) and, as a highly dense energy source, enable the reduction of glucose provision, thereby decreasing the risks of hyperglycemia and hepatic impairment. The prescription of LEs is complex, due mainly to their distinct FA components, which may alter the immune response in different ways and distinctly influence inflammation, oxidative stress and blood coagulation according to their biochemical properties. In addition, an excess of other LE components, such as phospholipids and phytosterols, may be associated with hepatic steatosis and dysfunction. These associations do not represent direct risks or obstacles to LE use in metabolically stable patients but can render the choice of the best LE for hypermetabolic patients difficult. The infusion of LEs according to the available guidelines provides more benefit than harm and should be part of exclusive parenteral nutrition regimens or complement enteral nutrition when appropriate. The patient's metabolic profile should guide the type of FA and amount of lipids that are provided. For critically ill hypermetabolic patients, growing evidence indicates that standard LEs based solely on soybean oil should be avoided in favor of new LEs containing medium-chain triglycerides, olive oil, or fish oil to decrease the provision of potentially oxidative, inflammatory/immunosuppressive, and prothrombotic n-6 FAs. In addition, as sources of eicosapentaenoic and docosahexaenoic acids, LEs containing fish oil may be important for critically ill patients because they allow better modulation of the immune response and likely reduce the length of intensive care unity stay. However, current evidence precludes the recommendation of a specific LE for clinical use in this patient population.

  1. Intravenous lipids in home parenteral nutrition.

    PubMed

    Pironi, Loris; Agostini, Federica; Guidetti, Mariacristina

    2015-01-01

    Intravenous lipid emulsions (IVLEs) are an important component of the nutritional admixtures for patients on long-term home parenteral nutrition (HPN) for chronic intestinal failure (CIF). IVLEs are primarily used as a source of energy and essential fatty acids, and the content of polyunsaturated fatty acids (PUFAs) is the most important characteristic of IVLEs. IVLEs rich in n-6 PUFAs may have a pro-inflammatory effect, whereas those rich in n-3 PUFAs may exert an anti-inflammatory effect. Other components to be considered are the risk of lipid peroxidation and the contents of α-tocopherol and phytosterols. Published studies were reviewed to determine the effects of the commercially available IVLEs on essential fatty acid status, liver function tests, lipid peroxidation and inflammatory indices, and α-tocopherol status, as well as their clinical safety and efficacy in patients on HPN. Investigations on the efficacy of fish oil-based IVLEs, which are rich in n-3 PUFAs, in the treatment of parenteral nutrition-associated liver disease (PNALD) in adult patients on HPN for CIF were also analyzed. The current commercial IVLE formulations have similar clinical safety profiles and efficacies and can prevent the development of essential fatty acid deficiency in adults on HPN for CIF. IVLE with a low content of n-6 PUFAs and with or without increased n-3 PUFA content may reduce the risk of PNALD. Fish oil-based IVLE, which is rich in n-3 PUFAs, may be effective in reversing hepatic cholestasis due to PNALD.

  2. “Early Trigger” Intravenous Vitamin K

    PubMed Central

    Diament, Marina; MacLeod, Kirsty; O’Hare, Jonathan; Tate, Anne

    2015-01-01

    Best practice tariff (BPT) was introduced as a financial incentive model to improve compliance with evidence-based care, such as operation for hip fracture within 36 hours of admission. We previously evaluated the impact of warfarin on patients with hip fracture, revealing significant delay to operation and subsequent loss of revenue. As a result of this, an “early trigger” intravenous vitamin K (IVK) pathway was introduced and the service reaudited a year later. The first cycle was a retrospective audit of all cases with hip fracture against BPT standards over a 32-month period. Subsequent protocol change resulted in all warfarinised cases being given 2 mg IVK in the emergency department prior to blood testing. This protocol was reaudited against the same BPT standards 12 months later. An intention-to-treat approach was used, despite breaches of protocol and other reasons for patients not progressing to theater. The data were analyzed with parametric tools to establish true clinical and statistical impact of the introduction of the protocol. In the first cycle, 80 patients were admitted on warfarin with a mean time to theater of 53.71 hours. Of these patients, 79% breached BPT due to anticoagulation. Twelve months following protocol introduction, 42 patients had a mean time to theater of 37.61 hours. Of these patients, 34% breached BPT due to anticoagulation. These data are both clinically and statistically significant (P < .001). No adverse events occurred. We have shown for the first time that “early-trigger” IVK can reduce delay to theater and maximize tariff payments in warfarinised patients with hip fracture. This is in addition to other established benefits associated with early surgery such as decreasing risk of pressure lesions and pneumonia. It affords high-quality patient-centered care while ensuring trauma units achieve maximal financial reimbursement through pay for improved performance and supports a culture of change behavior. PMID:26623160

  3. Etomidate: a new intravenous anesthetic induction agent.

    PubMed

    Giese, J L; Stanley, T H

    1983-01-01

    Currently available anesthetic induction agents provide adequate hypnosis but are not ideal, particularly in the high risk patient (ASA class III-V), because most cause myocardial and/or respiratory depression and some have other important side effects. Etomidate was recently marketed as an intravenous anesthetic induction agent. It is a non-barbiturate hypnotic without analgesic properties that has less cardiovascular and respiratory depressant actions than sodium thiopental, even in patients with minimal cardiovascular reserve. Laboratory studies indicate that etomidate is approximately 25 times more potent and has a therapeutic index six times greater than sodium thiopental. In contrast to most other induction agents, etomidate does not cause histamine release. Furthermore, tolerance does not occur with repeated administration. Etomidate's rapid distribution half life (t 1/2 alpha = 2.81 +/- 1.64 min), short elimination half life 1/2 beta = 3.88 +/- 1.11 hr) and rapid clearance (954 +/- 178 ml/min) explain its rapid onset and short duration of action. The compound produces electroencephalographic changes and effects on cerebral blood flow, metabolism and intracranial pressure that are similar to sodium thiopental, suggesting that it may have a place in neurosurgery and as a "brain protective" agent in patients at risk of a brain hypoxic insult. Etomidate did not affect hepatorenal and hematologic function after repeated injections in animal toxicology studies, but few investigations addressing its effects on hepatic, renal, and neuromuscular function in man have been accomplished. The most noticeable side effects of etomidate include myoclonia, pain on injection and postoperative nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Intravenous regional anaesthesia for lower limb orthopaedic surgery.

    PubMed Central

    Fagg, P. S.

    1987-01-01

    Intravenous regional anaesthesia in lower limb orthopaedic surgery has rarely been reported. A prospective series of 50 orthopaedic procedures performed with prilocaine is presented. In over 90% of patients excellent anaesthesia was obtained. PMID:3426092

  5. Clinical use of intravenous iron: administration, efficacy, and safety.

    PubMed

    Auerbach, Michael; Ballard, Harold

    2010-01-01

    This section reviews the history, pharmacology, administration, efficacy, and toxicity of intravenous iron. Intravenous iron offers advantages over oral iron for the treatment of iron deficiency anemia across a wide range of disease states associated with absolute and functional iron deficiency. However, there remain concerns about the acute safety profiles of the available preparations and the potential for long-term toxicity with their repeated administration. Seven intravenous iron formulations are available. Confusion concerning the relative toxicities of the different formulations abounds. The similarities and differences are discussed. Iron repletion has been associated with adverse outcomes in infections. The relationship, if any, between intravenous iron administration and infections is reviewed. The potential advantages of total dose infusion (TDI), complete repletion in a single setting, are highlighted. A new paradigm for iron replacement therapy in iron deficiency anemia is presented.

  6. Septicemia secondary to administration of a contaminated intravenous fluid.

    PubMed

    Lieblich, S E; Forman, D; Berger, J; Gold, B D

    1984-10-01

    The clinical entities of bacterial contamination, septicemia, and septic shock have been discussed, and an unusual case of septic shock has been presented. The associated risks of intravenous delivery of drugs or fluids are stressed.

  7. [Proposal for the formation of an intravenous therapy team].

    PubMed

    Carrero Caballero, M C

    2006-12-01

    At the present time, the medical profession is succeeding not only in helping the sick live longer but to have a higher quality of life, if possible inside their family environment. This requires a serious study regarding this situation. Many patients can receive intravenous treatment in outpatient clinics whenever these have a trustworthy system to administer intravenous pharmaceuticals, a system which provides safety and comfort to the patient and ease to the professionals which administer it.

  8. Intravenous pyogenic granuloma of the hand - a case report.

    PubMed

    Joethy, J; Al Jajeh, I; Tay, S C

    2011-01-01

    Intravenous pyogenic granuloma represents a variant of the common pyogenic granuloma in which the capillary proliferation is entirely confined to the lumen of a vein. To our knowledge, this entity is rare and only a few cases have been reported before in the hand. We present a case of intravenous pyogenic granuloma of the hand and a review of this entity from previous published cases.

  9. Monitoring of propofol and its metabolite during total intravenous anesthesia

    NASA Astrophysics Data System (ADS)

    Elizarov, A. Yu.; Ershov, T. D.; Levshankov, A. I.

    2011-12-01

    Intravenous hypnotic propofol and its metabolite are detected in real time during total intravenous anesthesia by an electron ionization mass spectrometer. The mass spectrometer is connected directly to the breathing circuit of an apparatus for inhalational anesthesia. Ratios between the propofol concentrations in expired air and blood serum are measured. It is concluded that real-time noninvasive monitoring of the propofol concentration in blood using electron ionization mass spectrometry is feasible.

  10. Relationship between intravenous use and achieving initial cocaine abstinence.

    PubMed

    Budney, A J; Higgins, S T; Bickel, W; Kent, L

    1993-04-01

    This study assessed whether route of cocaine administration (intravenous vs. intranasal) influences cocaine abstinence during the first 6 weeks of outpatient treatment. Fifty-nine persons received behavioral treatment or standard drug counselling in an outpatient clinic. Based on information collected at intake, intravenous users had fewer years of education, were employed in less skilled jobs, were less likely to be married, reported more negative consequences from cocaine use, reported using more cocaine per occasion and spent more money on cocaine per week than intranasal users. Intravenous and intranasal users did not differ significantly in the average duration of continuous cocaine abstinence (mean = 2.6 vs. mean = 3.3 weeks achieved during 6 weeks of treatment). The duration of abstinence between intravenous and intranasal users was equal in the behavioral treatment (mean = 4.2). In standard treatment the average duration was less among intravenous than intranasal users (mean = 0.9 vs. mean = 2.4), but that difference did not achieve statistical significance. Hepatitis and employment instability were associated with shorter periods of cocaine abstinence among intravenous users, whereas employment instability, lower job skill level, drug use severity and reports of memory loss were associated with shorter periods of cocaine abstinence among intranasal users. These results indicate that i.v. cocaine users can achieve a period of initial abstinence in an outpatient setting comparable to the duration of typical inpatient hospitalizations, although special types of outpatient treatment may be necessary to obtain a positive outcome.

  11. Dynamics of morphofunctional erythrocyte properties during intravenous glucose injection in patients with coronary heart disease

    NASA Astrophysics Data System (ADS)

    Malinova, Lidia I.; Simonenko, Georgy V.; Denisova, Tatyana P.; Tuchin, Valery V.

    2007-02-01

    Dynamics of glucose concentration in human organism is an important diagnostic characteristic for it's parameters correlate significantly with the severity of metabolic, vessel and perfusion disorders. 36 patients with stable angina pectoris of II and III functional classes were involved in this study. All of them were men in age range of 45-59 years old. 7 patients hospitalized with acute myocardial infarction (aged from 49 to 59 years old) form the group of compare. Control group (n = 5) was of practically healthy men in comparable age. To all patients intravenous glucose solution (40%) in standard loading dose was injected. Capillary and vein blood samples were withdrawn before, and 5, 60, 120, 180 and 240 minutes after glucose load. At these time points blood pressure and glucose concentration were measured. In prepared blood smears shape, deformability and sizes of erythrocytes, quantity and degree of shear stress resistant erythrocyte aggregates were studied. Received data were approximated by polynomial of high degree to receive concentration function of studied parameters, which first derivative elucidate velocity characteristics of morphofunctional erythrocyte properties during intravenous glucose injection in patients with coronary heart disease and practically healthy persons. Received data show principle differences in dynamics of morphofunctional erythrocyte properties during intravenous glucose injection in patients with coronary heart disease as a possible mechanism of coronary blood flow destabilization.

  12. Bioequivalence of Two Intravenous Artesunate Products with Its Active Metabolite Following Single and Multiple Injections

    PubMed Central

    Li, Qigui; Xie, Lisa; Melendez, Victor; Weina, Peter

    2011-01-01

    In animal species and humans, artesunate (AS) undergoes extensive and complex biotransformation to an active metabolite, dihydroartemisinin (DHA). The bioequivalence of two intravenous AS pharmaceutical products with 5% NaHCO3 (China Formulation) or 0.3 M PBS (WRAIR Formulation) was determined in rats in a two-formulation, two-period, and two-sequence crossover experimental design. Following single and multiple intravenous administrations, a series of blood samples was collected by using an automated blood sampler and drug concentrations were analyzed by LC-MS/MS. The 90% CI of the difference between the two intravenous formulations was contained within 80–125% of the geometric mean of pharmacokinetic parameters for AS and DHA in all animals dosed. Hematological effects were studied on days 1 and 3 after the final dosing, and a rapidly reversible hematological toxicity (significant reductions in reticulocyte levels) was seen in the peripheral blood of the rats treated with each formulation. The results showed that bioequivalence with the parent compound and active metabolite was fulfilled in the 82.3–117.7% ranges of all parameters (AUC0−t, Cmax, concentration average and degree of fluctuation) in the two-period and two-sequence crossover studies following single and repeated intravenous injections. For the metabolite, the equivalence was satisfied in most pharmacokinetic parameters tested due to the variability in the hydrolysis rate of AS to DHA. The WRAIR formulation of AS was considered to be bioequivalent to the Chinese formulation at steady-state according to the total drug exposure, in terms of both parent drug and active metabolite, rapidly reversal in reticulocyte decline, and extension of single and multiple administrations. Therefore, the parent drug and active metabolites should play similar important roles in the determination of efficacy and safety of the drug.

  13. No antidotal effect of intravenous lipid emulsion in experimental amitriptyline intoxication despite significant entrapment of amitriptyline.

    PubMed

    Litonius, Erik; Niiya, Tomohisa; Neuvonen, Pertti J; Rosenberg, Per H

    2012-04-01

    Intravenous lipid emulsion has been used in the resuscitative treatment of intoxications caused by local anaesthetics and tricyclic antidepressants with seemingly beneficial results. We studied the effect of intravenous lipid emulsion on the plasma concentration of amitriptyline and haemodynamic recovery in a pig model of amitriptyline intoxication. Twenty pigs were anaesthetized (1% isoflurane in 21% O(2)) and given amitriptyline 15 mg/kg intravenously for 15 min. In random fashion immediately thereafter, either 20% lipid emulsion (ClinOleic(®), Lipid group) or Ringer's acetate (Control group) was infused for 30 min.; first 1.5 ml/kg for 1 min., followed by 0.25 ml/kg/min. for 29 min. The amitriptyline concentration in total and lipid-poor plasma and haemodynamic parameters were measured until 30 min. after the infusions. Lipid infusion prevented the decrease in plasma total amitriptyline concentration, resulting in a 90% higher (p < 0.001) total concentration and significantly (p = 0.014) lower free fraction of plasma amitriptyline in the Lipid group (1.1%) compared with the Control group (3.0%) at 30 min. Haemodynamic recovery from the intoxication as measured by heart rate, arterial pressure or cardiac output was similar in both groups. However, five pigs in the Lipid group and two pigs in the Control group died. In conclusion, a marked entrapment of amitriptyline by intravenous lipid emulsion was observed but this did not improve the pigs' haemodynamic recovery from severe amitriptyline intoxication. Care should be exercised in the antidotal use of lipid emulsion until controlled human studies indicate its efficacy and safety.

  14. Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia.

    PubMed

    Friedrisch, João Ricardo; Cançado, Rodolfo Delfini

    2015-01-01

    Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15mg/kg; maximum of 1000mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia.

  15. Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia

    PubMed Central

    Friedrisch, João Ricardo; Cançado, Rodolfo Delfini

    2015-01-01

    Nutritional iron deficiency anemia is the most common deficiency disorder, affecting more than two billion people worldwide. Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia, but in many conditions, oral iron is less than ideal mainly because of gastrointestinal adverse events and the long course needed to treat the disease and replenish body iron stores. Intravenous iron compounds consist of an iron oxyhydroxide core, which is surrounded by a carbohydrate shell made of polymers such as dextran, sucrose or gluconate. The first iron product for intravenous use was the high molecular weight iron dextran. However, dextran-containing intravenous iron preparations are associated with an elevated risk of anaphylactic reactions, which made physicians reluctant to use intravenous iron for the treatment of iron deficiency anemia over many years. Intravenous ferric carboxymaltose is a stable complex with the advantage of being non-dextran-containing and a very low immunogenic potential and therefore not predisposed to anaphylactic reactions. Its properties permit the administration of large doses (15 mg/kg; maximum of 1000 mg/infusion) in a single and rapid session (15-minute infusion) without the requirement of a test dose. The purpose of this review is to discuss some pertinent issues in relation to the history, pharmacology, administration, efficacy, and safety profile of ferric carboxymaltose in the treatment of patients with iron deficiency anemia. PMID:26670403

  16. [Use of intravenous iron supplementation in chronic kidney disease: Interests, limits, and recommendations for a better practice].

    PubMed

    Rottembourg, Jacques; Rostoker, Guy

    2015-12-01

    Iron deficiency is an important clinical concern in chronic kidney disease (CKD), giving rise to iron-deficiency anaemia, and various impaired cellular functions. Oral supplementation, in particular with ferrous salts, is associated with a high rate of gastro-intestinal side effects and is poorly absorbed, a problem that is avoided with intravenous (IV) irons. Recently, with the approval of the European Medicines Agency's Committee for Medicinal Products for Human Use, the French Agence nationale de sécurité du médicament et des produits de santé (ANSM) took adequate measures to minimize the risk of allergic reactions, by correction on the summary of intravenous iron products characteristics. All IV iron products should be prescribed, administered and injected, inside public or private hospitals exclusively, and a clinical follow-up after the infusion for at least 30 minutes is mandatory. The most stable intravenous iron complexes (low molecular weight iron dextran, ferric carboxymaltose, and iron isomaltoside 1000 [under agreement]) can be given in higher single doses and more rapidly than less recent preparations such as iron sucrose (originator or similars). Test doses are advisable for conventional low molecular weight iron dextrans, but are no more mandatory. Iron supplementation is recommended for all CKD patients with iron-deficiency anaemia and those who receive erythropoiesis-stimulating agents, whether or not they require dialysis. Intravenous iron is the preferred route of administration in haemodialysis patients, with randomized trials showing a significantly greater increase in haemoglobin levels for intravenous versus oral iron and a low rate of treatment-related adverse events during these trials. According ANSM, physicians should apply the product's label recommendations especially the posology. In the non-dialysis CKD population, the erythropoietic response is also significantly higher using intravenous versus oral iron, and tolerability is at

  17. Comparison of oral and intravenous routes of giving tenoxicam.

    PubMed

    Kumara, R; Zacharias, M

    1998-06-01

    Twenty-five fit patients undergoing third molar surgery received the non-steroidal anti-inflammatory drug tenoxicam 40 mg given orally the night before surgery or intravenously at the time of surgery in a randomised, double-blind, cross-over trial. Propofol was used for intravenous sedation. Pain on injection was noted with propofol in 32-56 percent of subjects, but was mostly of minor nature. There was high (100 percent) acceptance of the method of sedation, with 60-84 percent rate of amnesia. Experience of post-operative pain, intake of medication, and trismus were similar with both methods of administration of tenoxicam. We conclude that both oral and intravenous administration of 40 mg tenoxicam are equally effective in healthy young patients undergoing third molar surgery.

  18. Intravenous iron therapy: well-tolerated, yet not harmless.

    PubMed

    Sengölge, G; Hörl, W H; Sunder-Plassmann, G

    2005-12-01

    In the majority of patients with chronic renal failure, it is essential to substitute erythropoietic agents and iron to maintain a haemoglobin level above 11 g dL-1. Intravenous iron is more effective than oral iron. Substitution of intravenous iron is mainly performed using iron(III)-hydroxide-sucrose complex (iron sucrose) and iron(III)-sodium-gluconate in sucrose (iron gluconate), and is, in general, well-tolerated. Nonetheless, intravenous iron therapy has effects on endothelial cells, polymorphonuclear leucocytes and cytokines which are most likely related to non-transferrin bound labile iron. These effects suggest a role of iron in infection or atherosclerosis. Yet, not all available data support the association of iron with infection and atherosclerosis. A recent trial showed that iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores. Nevertheless, iron therapy should be handled with caution but its use should not be feared whenever indicated.

  19. Intravenous methylprednisolone pulse therapy for children with epileptic encephalopathy

    PubMed Central

    Pera, Maria Carmela; Randazzo, Giovanna; Masnada, Silvia; Dontin, Serena Donetti; De Giorgis, Valentina; Balottin, Umberto; Veggiotti, Pierangelo

    2015-01-01

    Summary The aim of this retrospective study of children affected by epileptic encephalopathy was to evaluate seizure frequency, electroencephalographic pattern and neuropsychological status, before and after intravenous methylprednisolone therapy. Eleven children with epileptic encephalopathy were administered one cycle of intravenous methylprednisolone (15–30 mg/kg/day for three consecutive days, once a month for four months) in addition to constant dosages of their regular antiepileptic drugs. The treatment resulted in statistically significant reductions of generalized slow spike-and-wave discharges (p<0.0028) and seizure frequency (p<0.013), which persisted even after methylprednisolone pulse therapy was stopped. A globally positive outcome was noted in 9/11 patients (81.8%). This methylprednisolone treatment regimen did not cause significant or persistent adverse effects. We suggest that children with epileptic encephalopathy without an underlying structural lesion could be the best candidates for intravenous methylprednisolone pulse therapy. PMID:26910177

  20. Intravenous iron in digestive diseases: a clinical (re)view

    PubMed Central

    Gomollón, Fernando; Gisbert, Javier P.; García-Erce, José Antonio

    2010-01-01

    Intravenous iron has been considered dangerous by many clinicians. In the last two decades, considerable experience has been gained with new formulations in different clinical settings. Data from clinical trials, observational studies, and postmarketing surveillance studies demonstrate that intravenous iron is safe and effective to treat iron deficiency and iron deficiency anaemia. Iron deficiency is particularly common in many digestive diseases: oral iron often fails while transfusions are not without considerable risks. In particular, in inflammatory bowel diseases, there is enough evidence to recommend intravenous iron in moderate-to-severe iron deficiency anaemia, in intolerance to oral iron, and in patients needing quick recovery (pre-operative setting). New formulations make treatment even easier and more convenient. Recent guidelines are available for inflammatory bowel diseases, and new guidelines in acute and chronic gastrointestinal bleeding are needed. PMID:23251730

  1. Fatal myocardial infarction associated with intravenous N-acetylcysteine error

    PubMed Central

    2011-01-01

    Background N-acetylcysteine is used to treat acetaminophen toxicity and is available in both intravenous and oral formulations. Our report describes a patient treated with intravenous N-acetylcysteine for acetaminophen toxicity who died after an anaphylactoid reaction following initiation of the infusion. Objective Clinicians should be aware of potential complications when deciding on which formulation of N-acetylcysteine to administer. Case Report A 53-year-old male presented with altered mental status after an overdose of acetaminophen/hydrocodone and carisoprodol. He had an acetaminophen level of 49 mcg/ml with an unknown time of ingestion. The patient was admitted to the intensive care unit (ICU) on a naloxone drip and was started on intravenous N-acetylcysteine (NAC) at the presumed dose of 150 mg/kg. Shortly after initiating the NAC infusion, the patient developed periorbital edema, skin rash, and hypotension. The infusion of N-acetylcysteine was immediately stopped and the patient required emergent intubation. Resuscitation was begun with intravenous fluids followed by the initiation of phenylephrine. He developed ST elevation in the inferior leads on his ECG. This evolved into an inferior myocardial infarction by ECG and cardiac enzymes. Echocardiogram showed global, severe hypokinesis with an ejection fraction of less than 20% in a patient with no pre-existing cardiac history. Despite aggressive support, he died approximately 17 hours after the initiation of intravenous NAC. Further investigation found a 10-fold formulation error in his NAC loading dose. Conclusion The intravenous formulation of NAC has a higher probability of significant adverse effects and complications not described with the oral formulation. Clinicians should be aware of these potential complications when deciding on which formulation to administer. PMID:21878099

  2. Anaesthetic-related neuroprotection: intravenous or inhalational agents?

    PubMed

    Schifilliti, Daniela; Grasso, Giovanni; Conti, Alfredo; Fodale, Vincenzo

    2010-11-01

    In designing the anaesthetic plan for patients undergoing surgery, the choice of anaesthetic agent may often appear irrelevant and the best results obtained by the use of a technique or a drug with which the anaesthesia care provider is familiar. Nevertheless, in those surgical procedures (cardiopulmonary bypass, carotid surgery and cerebral aneurysm surgery) and clinical situations (subarachnoid haemorrhage, stroke, brain trauma and post-cardiac arrest resuscitation) where protecting the CNS is a priority, the choice of anaesthetic drug assumes a fundamental role. Treating patients with a neuroprotective agent may be a consideration in improving overall neurological outcome. Therefore, a clear understanding of the relative degree of protection provided by various agents becomes essential in deciding on the most appropriate anaesthetic treatment geared to these objectives. This article surveys the current literature on the effects of the most commonly used anaesthetic drugs (volatile and gaseous inhalation, and intravenous agents) with regard to their role in neuroprotection. A systematic search was performed in the MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINHAL®) and Cochrane Library databases using the following keywords: 'brain' (with the limits 'newborn' or 'infant' or 'child' or 'neonate' or 'neonatal' or 'animals') AND 'neurodegeneration' or 'apoptosis' or 'toxicity' or 'neuroprotection' in combination with individual drug names ('halothane', 'isoflurane', 'desflurane', 'sevoflurane', 'nitrous oxide', 'xenon', 'barbiturates', 'thiopental', 'propofol', 'ketamine'). Over 600 abstracts for articles published from January 1980 to April 2010, including studies in animals, humans and in vitro, were examined, but just over 100 of them were considered and reviewed for quality. Taken as a whole, the available data appear to indicate that anaesthetic drugs such as barbiturates, propofol, xenon and most volatile anaesthetics (halothane

  3. Determination of ADME and bioavailability following intravenous, oral, and dermal routes of exposure.

    PubMed

    Saghir, Shakil A

    2009-08-01

    Humans are exposed to chemicals either voluntarily or involuntarily through several routes. Therapeutic drugs are introduced into the human system via a number of routes including, but not limited to, oral, inhalation, intravenous (i.v.), topical, and subcutaneous. For occupational and environmental chemicals, the major routes of human exposure are inhalation, dermal, and oral. To determine the extent of exposure to chemicals, the concentration of the active molecules is measured in a biological medium. Determination of absolute and/or relative bioavailability of occupational and environmental chemical exposure through different routes is critical in understanding the risk to the general population of a low-level exposure to these chemicals. This unit describes typical protocol designs to generate data for the calculation of absorption, distribution, metabolism, and elimination (ADME) and absolute and relative bioavailability of chemicals when exposed through i.v., oral, and dermal routes.

  4. Suicide by injecting lispro insulin with an intravenous cannula.

    PubMed

    Behera, C; Swain, Rajanikanta; Mridha, Asit Ranjan; Pooniya, Shashank

    2015-09-01

    Suicide by injecting insulin is not uncommon both in diabetic and non-diabetic people. The victim usually uses an insulin syringe or a traditional syringe attached to a needle for the injection of insulin, of either animal or synthetic origin. We report a case of suicide by a non-diabetic physician by injecting lispro insulin through an intravenous cannula. To the best of our knowledge, the use of an intravenous cannula for the injection of insulin for suicide is unusual and is rarely reported in the medico-legal literature.

  5. Intravenous Adenosine for Surgical Management of Penetrating Heart Wounds

    PubMed Central

    Kokotsakis, John; Hountis, Panagiotis; Antonopoulos, Nikolaos; Skouteli, Elian; Athanasiou, Thanos; Lioulias, Achilleas

    2007-01-01

    Accurate suturing of penetrating cardiac injuries is difficult. Heart motion, ongoing blood loss, arrhythmias due to heart manipulation, and the near-death condition of the patient can all affect the outcome. Rapid intravenous injection of adenosine induces temporary asystole that enables placement of sutures in a motionless surgical field. Use of this technique improves surgical conditions, and it is faster than other methods. Herein, we describe our experience with the use of intravenous adenosine to successfully treat 3 patients who had penetrating heart wounds. PMID:17420798

  6. Relapsing thrombotic microangiopathy and intravenous sustained-release oxycodone

    PubMed Central

    Nataatmadja, Melissa; Divi, Dakshinamurthy

    2016-01-01

    Thrombotic microangiopathy (TMA) associated with injecting sustained-release oxymorphone, an opioid intended for oral use, has previously been reported. We report a case of TMA secondary to intravenous use of sustained-release oxycodone, and the first case to demonstrate relapsing disease due to persistent intravenous opioid use. In cases such as these, TMA is suspected to be due to a polyethylene oxide (PEO) coating found on these drugs, and the disease is likely due to a directly toxic effect of PEO to endothelial cells. We hypothesize that there are unidentified genetic predispositions causing some persons to be susceptible to developing this disease. PMID:27478601

  7. Response to intravenous midazolam sedation in general dental practice.

    PubMed

    Ellis, S

    1996-06-08

    The object of this study was to grade the response of patients undergoing a variety of dental procedures with the aid of intravenous midazolam sedation in general dental practice and to explore any relationships between the patients preoperative anxiety assessment and the clinician's assessment of co-operation whilst under sedation. One hundred consecutive patients aged between 18 and 58 years (mean 32 years; sd 10 years) and in ASA Class I or II were prospectively studied. Results showed that despite attempts to grade patient's behaviour it was not possible to reliably predict patient's responses under intravenous sedation. In addition to these findings, the great individual variation in sensitivity to midazolam was confirmed.

  8. The patient: Emerging clinical applications of intravenous immunoglobulin.

    PubMed

    Harvey, R Donald

    2005-11-01

    Intravenous immunoglobulin (IGIV) originally was used as prophylactic treatment of infections in patients with primary immunodeficiency disease. Today, administration of IGIV, due in large part to its immunomodulatory activity, has expanded to include a number of other disorders. Available data suggest that the accepted indications for IGIV will continue to expand. As the number of clinical applications for this therapy grows, so will market opportunities; current preparations will be modified and improved and new products introduced. Intravenous immunoglobulin therapy has improved the lives of many patients with immune-related disorders. Future applications will ideally advance this paradigm further.

  9. [The development of multifunction intravenous infusion quantitative packaging device].

    PubMed

    Zhao, Shufang; Li, Ruihua; Shen, Lianhong

    2012-11-01

    Aimed at tackling the compatibility issues arising from the drug reaction in intravenous infusion tube, we developed a simple, suitable and multi-function intravenous infusion tube for the special use for rescuing critical patients, the elderly, children etc. Each drug in a transfusion process can be filtered to realize quantitative packet and packet delivery. Thus, the drugs in the infusion tube are prevented from meeting with each other. No overlap, no particle pollution occurred. Stable performance and accurate dosage are maintained. As a result safety is ensured during drug delivery.

  10. Intravenous Ghrelin Administration Increases Alcohol Craving in Alcohol-Dependent Heavy Drinkers: a Preliminary Investigation

    PubMed Central

    Leggio, Lorenzo; Zywiak, William H.; Fricchione, Samuel R.; Edwards, Steven M.; de la Monte, Suzanne M.; Swift, Robert M.; Kenna, George A.

    2014-01-01

    Background There is a need to identify novel pharmacological targets to treat alcoholism. Animal and human studies suggest a role of ghrelin in the neurobiology of alcohol dependence and craving. Here, we were the first to test the hypothesis that intravenous administration of exogenous ghrelin acutely increases alcohol craving. Methods This was a double-blind placebo-controlled human laboratory proof-of-concept study. Non-treatment seeking alcohol-dependent heavy drinking individuals were randomized to receive intravenous ghrelin 1mcg/kg, 3 mcg/kg or 0 mcg/kg (placebo), followed by a cuereactivity procedure, during which participants were exposed to neutral (juice) and alcohol cues. The primary outcome variable was the increase in alcohol craving (also called “urge”) for alcohol, assessed by the Alcohol Visual Analogue Scale. Results Out of 103 screenings, 45 individuals received the study drug. Repeated measures of ANCOVA revealed a group effect across ghrelin doses in increasing alcohol craving (p < .05). A dose-specific examination revealed a significant effect of ghrelin 3 mcg/kg vs. placebo in increasing alcohol craving (p < .05) with a large effect size (d = .94). By contrast, no significant ghrelin effect was found in increasing either urge to drink juice or food craving (p: n.s.). No significant differences in side effects were found (p: n.s.). Conclusions Intravenous administration of exogenous ghrelin increased alcohol craving in alcohol-dependent heavy drinking individuals. Although the small sample requires confirmatory studies, these findings provide preliminary evidence that ghrelin may play a role in the neurobiology of alcohol craving, thus demonstrating a novel pharmacological target for treatment. PMID:24775991

  11. Effects of Intravenous Injection of Porphyromonas gingivalis on Rabbit Inflammatory Immune Response and Atherosclerosis

    PubMed Central

    Lin, Gengbing; Chen, Shuai; Lei, Lang; You, Xiaoqing; Huang, Min; Luo, Lan; Li, Yanfen; Zhao, Xin; Yan, Fuhua

    2015-01-01

    The effects of intravenous injection of Porphyromonas gingivalis (Pg) on rabbit inflammatory immune response and atherosclerosis were evaluated by establishing a microamount Pg bacteremia model combined with high-fat diet. Twenty-four New Zealand rabbits were randomly divided into Groups A-D (n = 6). After 14 weeks, levels of inflammatory factors (C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1)) in peripheral blood were detected by ELISA. The aorta was subjected to HE staining. Local aortic expressions of toll-like receptor-2 (TLR-2), TLR-4, TNF-α, CRP, IL-6, matrix metallopeptidase-9, and MCP-1 were detected by real-time PCR, and those of nuclear factor-κB (NF-κB) p65, phospho-p38 mitogen-activated protein kinase (MAPK), and phospho-c-Jun N-terminal kinase (JNK) proteins were detected by Western blot. Intravenous injection of Pg to the bloodstream alone induced atherosclerotic changes and significantly increased systemic and local aortic expressions of inflammatory factors, NF-κB p65, phospho-p38-MAPK, and JNK, especially in Group D. Injection of microamount Pg induced inflammatory immune response and accelerated atherosclerosis, in which the NF-κB p65, p38-MAPK, and JNK signaling pathways played important roles. Intravenous injection of Pg is not the same as Pg from human periodontitis entering the blood stream. Therefore, our results cannot be extrapolated to human periodontitis. PMID:26063970

  12. The new generation of liquid intravenous immunoglobulin formulations in patient care: a comparison of intravenous immunoglobulins.

    PubMed

    Stein, Mark R

    2010-09-01

    Intravenous immunoglobulin (IGIV) replacement therapy is the standard of care for primary immunodeficiencies with impaired humoral immunity. It is also the immunomodulatory therapy of choice for some types of neuroimmunologic and autoimmune hematologic disorders and for immunomodulation in bone marrow and some solid organ transplants. Currently available IGIV products include older lyophilized formulations, 5% liquid products, and newer, liquid, ready-to-use, 10% formulations. Differences in the formulations, manufacturing processes, excipients, pH, and other physicochemical properties of IGIV products may affect their clinical efficacy and tolerability. Among at-risk patients, the possibility of serious complications such as renal insufficiency, heart failure, thrombotic events, and immunological reactions may be increased if an IGIV formulation has sugar as a stabilizer, has high sodium or immunoglobulin A (IgA) content, or is hyperosmolar. The 10% liquid formulations may offer advantages because of their lower IgA concentrations, optimal pH, glycine or proline stabilizers, low sodium content, and lower osmolality. Liquid formulations are more convenient for patients and health care providers due to shorter infusion times and easier preparation and administration.

  13. Intravenous multipotent adult progenitor cell treatment decreases inflammation leading to functional recovery following spinal cord injury

    PubMed Central

    DePaul, Marc A.; Palmer, Marc; Lang, Bradley T.; Cutrone, Rochelle; Tran, Amanda P.; Madalena, Kathryn M.; Bogaerts, Annelies; Hamilton, Jason A.; Deans, Robert J.; Mays, Robert W.; Busch, Sarah A.; Silver, Jerry

    2015-01-01

    Following spinal cord injury (SCI), immune-mediated secondary processes exacerbate the extent of permanent neurological deficits. We investigated the capacity of adult bone marrow-derived stem cells, which exhibit immunomodulatory properties, to alter inflammation and promote recovery following SCI. In vitro, we show that human multipotent adult progenitor cells (MAPCs) have the ability to modulate macrophage activation, and prior exposure to MAPC secreted factors can reduce macrophage-mediated axonal dieback of dystrophic axons. Using a contusion model of SCI, we found that intravenous delivery of MAPCs one day, but not immediately, after SCI significantly improves urinary and locomotor recovery, which was associated with marked spinal cord tissue sparing. Intravenous MAPCs altered the immune response in the spinal cord and periphery, however biodistribution studies revealed that no MAPCs were found in the cord and instead preferentially homed to the spleen. Our results demonstrate that MAPCs exert their primary effects in the periphery and provide strong support for the use of these cells in acute human contusive SCI. PMID:26582249

  14. Stability of ceftiofur sodium and cefquinome sulphate in intravenous solutions.

    PubMed

    Dołhań, Agnieszka; Jelińska, Anna; Bębenek, Marcelina

    2014-01-01

    Stability of ceftiofur sodium and cefquinome sulphate in intravenous solutions was studied. Chromatographic separation and quantitative determination were performed by using a high-performance liquid chromatography with UV-DAD detection. During the stability study, poly(vinylchloride) minibags were filled with a solution containing 5 mg of ceftiofur sodium or cefquinome sulphate and diluted to 0.2 mg/mL with suitable intravenous solution depending on the test conditions. The solutions for the study were protected from light and stored at room temperature (22°C), refrigerated (6°C), frozen (-20°C) for 30 days, and then thawed at room temperature. A comparison of results obtained at 22°C and 6°C for the same intravenous solutions showed that temperature as well as components of solutions and their concentration had an influence on the stability of ceftiofur sodium and cefquinome sulphate. It was found that ceftiofur sodium and cefquinome sulphate dissolved in intravenous solutions used in this study may be stored at room temperature and at 6°C for up to 48 h.

  15. Intravenous Sedation for Dental Patients with Intellectual Disability

    ERIC Educational Resources Information Center

    Miyawaki, T.; Kohjitani, A.; Maeda, S.; Egusa, M.; Mori, T.; Higuchi, H.; Kita, F.; Shimada, M.

    2004-01-01

    The poor quality of oral health care for people with intellectual disability (ID) has been recognized, and the strong fears about dental treatment suggested as a major reason for disturbances of visits to dentists by such patients. Intravenous sedation is a useful method for relieving the anxiety and fear of such patients about dental treatment,…

  16. A case of dermatomyositis with rhabdomyolysis, rescued by intravenous immunoglobulin.

    PubMed

    Mizoguchi, Fumitaka; Takada, Kazuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Kohsaka, Hitoshi; Miyasaka, Nobuyuki

    2015-07-01

    We describe a case of severe dermatomyositis (DM) complicated by rhabdomyolysis, acute tubular necrosis, and hemophagocytosis. The case failed to respond to corticosteroids, but showed rapid and significant improvement after the addition of intravenous immunoglobulin (IVIG). While the prognosis of DM is poor when it is complicated by rhabdomyolysis, the early administration of IVIG has the potential to be the cornerstone of its management.

  17. Intravenous Therapy Instruction for Licensed Practical Nurses. Instructor's Guide.

    ERIC Educational Resources Information Center

    Springer, Pam; Carey, Jean

    This Idaho instructor's guide lists tasks and enabling objectives, outlines instruction, and provides handout masters, overhead masters, and tests for intravenous therapy (IV) instruction for licensed practical nurses. Following an introduction and a list of criteria for successful completion of IV therapy courses, the document lists tasks and…

  18. Stability of Ceftiofur Sodium and Cefquinome Sulphate in Intravenous Solutions

    PubMed Central

    Jelińska, Anna; Bębenek, Marcelina

    2014-01-01

    Stability of ceftiofur sodium and cefquinome sulphate in intravenous solutions was studied. Chromatographic separation and quantitative determination were performed by using a high-performance liquid chromatography with UV-DAD detection. During the stability study, poly(vinylchloride) minibags were filled with a solution containing 5 mg of ceftiofur sodium or cefquinome sulphate and diluted to 0.2 mg/mL with suitable intravenous solution depending on the test conditions. The solutions for the study were protected from light and stored at room temperature (22°C), refrigerated (6°C), frozen (−20°C) for 30 days, and then thawed at room temperature. A comparison of results obtained at 22°C and 6°C for the same intravenous solutions showed that temperature as well as components of solutions and their concentration had an influence on the stability of ceftiofur sodium and cefquinome sulphate. It was found that ceftiofur sodium and cefquinome sulphate dissolved in intravenous solutions used in this study may be stored at room temperature and at 6°C for up to 48 h. PMID:25025091

  19. Intravenous Cocaine Priming Reinstates Cocaine-Induced Conditioned Place Preference

    ERIC Educational Resources Information Center

    Lombas, Andres S.; Freeman, Kevin B.; Roma, Peter G.; Riley, Anthony L.

    2007-01-01

    Separate groups of rats underwent an unbiased conditioned place preference (CPP) procedure involving alternate pairings of distinct environments with intravenous (IV) injections of cocaine (0.75 mg/kg) or saline immediately or 15 min after injection. A subsequent extinction phase consisted of exposure to both conditioning environments preceded by…

  20. Intravenous sedation in 200 geriatric patients undergoing office oral surgery.

    PubMed

    Campbell, R L; Smith, P B

    1997-01-01

    Two hundred geriatric patients ranging from age 65 to 92 yr (mean age 72 yr) were evaluated for office oral surgery and intravenous sedation. Surgical time ranged from 6 to 129 min. Monitored anesthesia care was utilized for the administration of fentanyl, midazolam or diazepam, and methohexital. No serious complications were seen and no patients were hospitalized.

  1. Oxalic acid excretion after intravenous ascorbic acid administration.

    PubMed

    Robitaille, Line; Mamer, Orval A; Miller, Wilson H; Levine, Mark; Assouline, Sarit; Melnychuk, David; Rousseau, Caroline; Hoffer, L John

    2009-02-01

    Ascorbic acid is frequently administered intravenously by alternative health practitioners and, occasionally, by mainstream physicians. Intravenous administration can greatly increase the amount of ascorbic acid that reaches the circulation, potentially increasing the risk of oxalate crystallization in the urinary space. To investigate this possibility, we developed gas chromatography mass spectrometry methodology and sampling and storage procedures for oxalic acid analysis without interference from ascorbic acid and measured urinary oxalic acid excretion in people administered intravenous ascorbic acid in doses ranging from 0.2 to 1.5 g/kg body weight. In vitro oxidation of ascorbic acid to oxalic acid did not occur when urine samples were brought immediately to pH less than 2 and stored at -30 degrees C within 6 hours. Even very high ascorbic acid concentrations did not interfere with the analysis when oxalic acid extraction was carried out at pH 1. As measured during and over the 6 hours after ascorbic acid infusions, urinary oxalic acid excretion increased with increasing doses, reaching approximately 80 mg at a dose of approximately 100 g. We conclude that, when studied using correct procedures for sample handling, storage, and analysis, less than 0.5% of a very large intravenous dose of ascorbic acid is recovered as urinary oxalic acid in people with normal renal function.

  2. Foreign body aspiration pneumonia in an intravenous drug user

    PubMed Central

    Bhaskar, Balu; Andelkovic, Vladimir

    2012-01-01

    Heroin use is associated with several well described respiratory complications, including noncardiogenic pulmonary edema, aspiration pneumonitis, acute respiratory distress syndrome,pneumonia, lung abscess, septic pulmonary emboli, and atelectasis. We describe an interesting case of a young female patient, an intravenous heroin user who presented with progressive dyspnea, hypoxia, and left lung consolidation. PMID:22412782

  3. Self-injection of intravenous carbolic acid and multiorgan failure

    PubMed Central

    Ghosh, Supradip

    2014-01-01

    Intravenous self-injection of phenol resulting in multi-organ failure is reported. The case is discussed, because of the unique nature of exposure to phenol and rapid involvement of multiple organ systems including the central nervous,pulmonary, renal and hematological systems. PMID:24550614

  4. Hyperphenylalaninaemia and outcome in intravenously fed preterm neonates.

    PubMed

    Lucas, A; Baker, B A; Morley, R M

    1993-05-01

    Hyperphenylalaninaemia is likely to have occurred in many infants fed the intravenous amino acid solution Vamin 9. In this study of 336 preterm infants plasma phenylalanine was measured weekly during their hospital stay. Reference data on plasma phenylalanine were prepared for 243 infants who did not receive Vamin. Only 1% of these infants had a peak plasma phenylalanine concentration greater than 150 mumol/l (maximum 202 mumol/l) compared with 23% in 93 infants fed Vamin 9, seven of whom had concentrations > 300 mumol/l (maximum 704 mumol/l). High concentrations only occurred when the total energy to protein energy ratio in the intravenous solutions decreased to less than 8.5:1 and always occurred with a ratio less than 6.5:1, implying that hyperphenylalaninaemia may be minimised with an intravenous energy intake of greater than 34 kcal (142 kJ)/g protein. Nevertheless, follow up at 18 months post-term showed that increased plasma phenylalanine in this instance was not associated with any impairment of the Bayley mental development index (or subscales including fine motor, cognitive, or language development), the psychomotor development index, or the social maturity quotient. Thus, despite theoretical concern, an adverse outcome after hyperphenylalaninaemia induced by intravenous feeding has not been observed.

  5. Hyperphenylalaninaemia and outcome in intravenously fed preterm neonates.

    PubMed Central

    Lucas, A; Baker, B A; Morley, R M

    1993-01-01

    Hyperphenylalaninaemia is likely to have occurred in many infants fed the intravenous amino acid solution Vamin 9. In this study of 336 preterm infants plasma phenylalanine was measured weekly during their hospital stay. Reference data on plasma phenylalanine were prepared for 243 infants who did not receive Vamin. Only 1% of these infants had a peak plasma phenylalanine concentration greater than 150 mumol/l (maximum 202 mumol/l) compared with 23% in 93 infants fed Vamin 9, seven of whom had concentrations > 300 mumol/l (maximum 704 mumol/l). High concentrations only occurred when the total energy to protein energy ratio in the intravenous solutions decreased to less than 8.5:1 and always occurred with a ratio less than 6.5:1, implying that hyperphenylalaninaemia may be minimised with an intravenous energy intake of greater than 34 kcal (142 kJ)/g protein. Nevertheless, follow up at 18 months post-term showed that increased plasma phenylalanine in this instance was not associated with any impairment of the Bayley mental development index (or subscales including fine motor, cognitive, or language development), the psychomotor development index, or the social maturity quotient. Thus, despite theoretical concern, an adverse outcome after hyperphenylalaninaemia induced by intravenous feeding has not been observed. PMID:8323359

  6. The use of a small programmable calculator in intravenous feeding.

    PubMed

    Goggin, M J

    1979-01-01

    This paper describes a method using a programmable calculator to determine intravenous nutritional requirements of severely ill patients. A description of the method and calculations used is given. The advantages of this system are shown to lie in its easy availability to all hospital departments.

  7. Intravenous hemostats: challenges in translation to patients

    NASA Astrophysics Data System (ADS)

    Lashof-Sullivan, Margaret; Shoffstall, Andrew; Lavik, Erin

    2013-10-01

    must be resolved before these types of particles can be translated for human use.

  8. Intravenous non-opioid analgesia for peri- and postoperative pain management: a scientific review of intravenous acetaminophen and ibuprofen

    PubMed Central

    Koh, Wonuk; Nguyen, Kimngan Pham

    2015-01-01

    Pain is a predictable consequence following operations, but the management of postoperative pain is another challenge for anesthesiologists and inappropriately controlled pain may lead to unwanted outcomes in the postoperative period. Opioids are indeed still at the mainstream of postoperative pain control, but solely using only opioids for postoperative pain management may be connected with risks of complications and adverse effects. As a consequence, the concept of multimodal analgesia has been proposed and is recommended whenever possible. Acetaminophen is one of the most commonly used analgesic and antipyretic drug for its good tolerance and high safety profiles. The introduction of intravenous form of acetaminophen has led to a wider flexibility of its use during peri- and postoperative periods, allowing the early initiation of multimodal analgesia. Many studies have revealed the efficacy, safety and opioid sparing effects of intravenous acetaminophen. Intravenous ibuprofen has also shown to be well tolerated and demonstrated to have significant opioid sparing effects during the postoperative period. However, the number of randomized controlled trials confirming the efficacy and safety is small and should be used in caution in certain group of patients. Intravenous acetaminophen and ibuprofen are important options for multimodal postoperative analgesia, improving pain and patient satisfaction. PMID:25664148

  9. Phase I study of intermittent intravenous bromodeoxyuridine (BUdR) with conventional fractionated irradiation

    SciTech Connect

    Kinsella, T.J.; Russo, A.; Mitchell, J.B.; Rowland, J.; Jenkins, J.; Schwade, J.; Myers, C.E.; Collins, J.M.; Speyer, J.; Kornblith, M.D.

    1984-01-01

    A Phase I trial of intravenous bromodeoxyuridine (BUdR) and conventional fractionated radiation therapy was performed in 14 patients with glioblastoma multiforme and 7 patients with other poorly radioresponsive tumors. The BUdR was given as a constant intravenous infusion for 12 hr/day for up to 14 days. Local toxicity (within the radiation field) was minor, with 7 of the 21 patients requiring a brief treatment break for moist skin desquamation. There was no significant CNS toxicity noted clinically nor by autopsy examination. Additionally, no significant enhancement of radiation injury was noted to bowel or liver. Dose-dependent systemic toxicity occurred in bone marrow and skin. Moderate myelosuppression, especially thrombocytopenia, was found following a 14 day cycle of BUdR at and above 650 mg/m/sup 2//12 hr infusion. Approximately one-third of patients developed a maculo-papular erythematous rash to the scalp, neck and upper chest. Pharmacology studies revealed steady-state arterial plasma levels of 2 x 10/sup -6/M/1 during the 12 hr infusion of 650 to 700 mg/m/sup 2/. Radiosensitization was measured by a change in the D/sub 0/ of radiation survival curves of human bone marrow CFUc prior to and following the 14 day infusion in 4 patients. A trend of increasing radiosensitization was noted in most patients as the infusion rate of BUdR was increased from 500 to 870 mg/m/sup 2//12 hr. It is concluded that the maximum tolerable dose of BUdR is 650 to 700 mg/m/sup 2//12 hrs when given as a 2 week intermittent intravenous infusion. Local toxicity is acceptable. The major systemic toxicities are myelosuppression and a maculopapular skin rash.

  10. Drug Audit of Intravenous Anaesthetic Agents in Tertiary Care Hospital

    PubMed Central

    Dabhade, Sangeeta Sanjay; Ghongane, Balasaheb Baburao

    2015-01-01

    Introduction Drug cost is essential component of anaesthesia pharmacoeconomics. Recently pharmacoeconomics has emerged to measure, compare and evaluate cost of drug therapy to health system and decide which strategies produce best outcomes for resources allocated. The present study was planned to find utilization of intravenous anaesthetic agents in a tertiary care hospital and to find the pharmacoeconomics related to utilized and un-utilized drug data. Materials and Methods Prospective observational study was conducted for 3 months and 200 cases were recorded undergoing surgical procedures under general anaesthesia only. Intravenous drugs were considered excluding inhalational anaesthetics. Data for drug utilized and un-utilized was collected. Cost estimation was done. Results Thiopentone sodium was frequently used intravenous inducing anaesthetic agent in 75% of patients. On average 6.5 drugs were prescribed per patient as pre-anaesthetic and intravenous inducing anaesthetic medications. 100% of drugs were prescribed by generic name, 92.30% were from National Essential Drug List. Amongst intravenous anaesthetic agents maximum wastage was associated with propofol of about 36.59% and in pre-anaesthetics, wastage was maximum for atropine 79% followed by glycopyrrolate 45.95%, pentazocine 45.95%. The cost of wasted drugs for study duration was 29.82% (Rs. 10,276.25) of the total cost of drugs was loaded (Rs.34458.84). Of this, the cost of wastage of vecuronium was maximum being 16.82% (Rs.1728) of the total cost wastage, followed by rocuronium 15.38% (Rs.1580.80), glycopyrrolate 15.22% (Rs.1564), and neostigmine 10.95% (Rs.1125.12). The cost of wasted drug per case was maximum for rocuronium being Rs.158.08 and least for ketamine Rs. 1.18. Conclusion There is need to formulate indicators for intravenous anaesthetic agents utilization. The most commonly prescribed drug glycopyrrolate is still not in National Essential Drug List. The judicious use of these drugs and

  11. Intravenous infusion of H2-saline suppresses oxidative stress and elevates antioxidant potential in Thoroughbred horses after racing exercise.

    PubMed

    Yamazaki, Masahiko; Kusano, Kanichi; Ishibashi, Toru; Kiuchi, Masataka; Koyama, Katsuhiro

    2015-10-23

    Upon intensive, exhaustive exercise, exercise-induced reactive oxygen species may exceed the antioxidant defence threshold, consequently resulting in muscular damage or late-onset chronic inflammation. Recently, the therapeutic antioxidant and anti-inflammatory effects of molecular hydrogen (H2) for human rheumatoid arthritis have been demonstrated. However, it is also important to clarify the effects of administrating H2 in large animals other than humans, as H2 is thought to reach the target organ by passive diffusion upon delivery from the blood flow, indicating that the distance from the administration point to the target is critical. However, data on the effects of H2 on oxidative stress in real-life exhaustive exercise in large animals are currently lacking. We here investigated 13 Thoroughbred horses administered intravenous 2-L saline with or without 0.6-ppm H2 (placebo, N = 6; H2, N = 7) before participating in a high-intensity simulation race. Intravenous H2-saline significantly suppressed oxidative stress immediately, 3 h, and 24 h after the race, although the antioxidant capability was not affected throughout the study. The serum creatine kinase, lactate, and uric acid levels were increased in both groups. Taken together, these results indicate that intravenous H2-saline can significantly and specifically suppress oxidative stress induced after exhaustive racing in Thoroughbred horses.

  12. Intravenous infusion of H2-saline suppresses oxidative stress and elevates antioxidant potential in Thoroughbred horses after racing exercise

    PubMed Central

    Yamazaki, Masahiko; Kusano, Kanichi; Ishibashi, Toru; Kiuchi, Masataka; Koyama, Katsuhiro

    2015-01-01

    Upon intensive, exhaustive exercise, exercise-induced reactive oxygen species may exceed the antioxidant defence threshold, consequently resulting in muscular damage or late-onset chronic inflammation. Recently, the therapeutic antioxidant and anti-inflammatory effects of molecular hydrogen (H2) for human rheumatoid arthritis have been demonstrated. However, it is also important to clarify the effects of administrating H2 in large animals other than humans, as H2 is thought to reach the target organ by passive diffusion upon delivery from the blood flow, indicating that the distance from the administration point to the target is critical. However, data on the effects of H2 on oxidative stress in real-life exhaustive exercise in large animals are currently lacking. We here investigated 13 Thoroughbred horses administered intravenous 2-L saline with or without 0.6-ppm H2 (placebo, N = 6; H2, N = 7) before participating in a high-intensity simulation race. Intravenous H2-saline significantly suppressed oxidative stress immediately, 3 h, and 24 h after the race, although the antioxidant capability was not affected throughout the study. The serum creatine kinase, lactate, and uric acid levels were increased in both groups. Taken together, these results indicate that intravenous H2-saline can significantly and specifically suppress oxidative stress induced after exhaustive racing in Thoroughbred horses. PMID:26493164

  13. Brain blood flow measured with intravenous H/sub 2/ /sup 15/O. II. Implementation and validation

    SciTech Connect

    Raichle, M.E.; Martin, W.R.W.; Herscovitch, P.; Mintun, M.A.; Markham, J.

    1983-09-01

    The well-known tissue autoradiographic technique for the measurement of regional cerebral blood flow (CBF), originally proposed by Kety and his colleagues has been adapted for the measurement of CBF in human subjects using positron emission tomography (PET) and intravenously administered oxygen-15-labeled water. This report describes the steps necessary for the implementation of this PET/autoradiographic technique. In order to establish the accuracy of the method, we measured CBF with intravenously administered oxygen-15-labeled water and PET in anesthetized adult baboons and compared the results with blood flow measured by a standard tracer technique that uses residue detection of a bolus of oxygen-15-labeled water injected into the internal carotid artery. The correlation between CBF measured with PET and the true CBF for the same cerebral hemisphere was excellent.

  14. Management and prevention of complications of subcutaneous intravenous infusion port.

    PubMed

    Jan, Hsiang-Chun; Chou, Shao-Jiun; Chen, Tzu-Hung; Lee, Chuin-I; Chen, Tze-Kai; Lou, Mary Ann

    2012-03-01

    Subcutaneous intravenous infusion port (SIIP) has become an increasingly and widely adopted technique in the management of oncology patients. This route has been used not only for chemotherapy but also for parenteral nutrition provision, blood transfusion, medication administration, blood sample collection, hemodialysis, and so on. This system provides a safe vascular access with low complication rate which helps preventing patients from vascular infection and catheter associated thrombosis. In this study, we reviewed 1247 cases of breast cancer patients that had subcutaneous intravenous infusion port implanted for chemotherapy in our general surgery department from 1990 to 2008. The result indicates that complication decreases as our technique and experience mature. We hereby share our accrued experience and improved technique, hoping to be of help to young surgeons.

  15. Candida lusitaniae arthritis in an intravenous drug user.

    PubMed

    Jeragh, A; Ahmad, S; Naseem, J; Khan, Z U

    2007-09-01

    A case of arthritis of the right knee caused by Candida lusitaniae in a 29-year-old intravenous drug abuser is described. The diagnosis was based on the isolation of C. lusitaniae from synovial fluid and was supported by the presence of C. lusitaniae-specific DNA and high levels of (1-3)-beta-d-glucan (122 pg ml-1) in the same specimen. While the isolate was susceptible to amphotericin B and fluconazole in vitro, treatment with amphotericin B was not very effective. The patient achieved complete cure with fluconazole therapy only after undergoing synovectomy. To the best of our knowledge, this is the first report of arthritis caused by C. lusitaniae in an intravenous drug user.

  16. Scurvy in an alcoholic patient treated with intravenous vitamins.

    PubMed

    Ong, John; Randhawa, Rabinder

    2014-04-11

    Vitamin C deficiency is rare in developed countries but there is an increased prevalence in chronic alcohol abusers. In the UK, it is common practice to treat patients with chronic alcoholism who are admitted to hospital with intravenous vitamins B1, B2, B3, B6 and C for 2-3 days, followed by oral thiamine and vitamin B-compound tablets. This is a case of a 57-year-old man with a history of chronic alcoholism and chronic obstructive lung disease who was admitted to the intensive care unit for pneumonia requiring ventilatory support. He was given high doses of intravenous vitamins B1, B2, B3, B6 and C for 3 days then oral thiamine and vitamin B compound tablets but developed scurvy 4 days later. He was restarted on oral vitamin C supplementation and showed signs of improvement within 3 days of treatment.

  17. Dropped head with positive intravenous edrophonium, progressing to myasthenia gravis.

    PubMed

    Sawa, Nobuhiro; Kataoka, Hiroshi; Eura, Nobuyuki; Ueno, Satoshi

    2013-01-31

    'Dropped head syndrome' (DHS) may be associated with a variety of neurological diseases. The absence of neurological clues to the underlying cause of DHS can make management particularly challenging. We review six patients who presented with only DHS, responded to intravenous edrophonium and turned out to have myasthenia gravis (MG) including similar patients who were previously documented. Six patients presented with neck weakness and three had bulbar symptoms. Acetylcholine receptor (AchR) was positive in four patients. One patient had thymoma. The interval from the onset of DH to the presentation of typical MG features was shorter in patients who tested positive for anti-Ach antibody (1-2 months) than in patients who tested negative for anti-AchR antibody (13 months, 4 years). Our results suggest that patients with DHS responding to intravenous edrophonium might turn out to have MG and such patients might respond to a combination of anticholinesterase agents and steroids.

  18. Titration of vaccinia virus by intravenous injection of chick embryos

    PubMed Central

    Kaplan, C.

    1960-01-01

    The final test of a smallpox vaccine is its capacity to prevent the disease from developing in inoculated individuals. This capacity, however, cannot be measured directly, so that other methods of assessing the efficacy of vaccine have had to be developed. A laboratory method—pock counting on the chorio-allantoic membrane of chick embryos—has recently been shown to provide a reasonably reliable estimate of the number of infective units in a given vaccine. In this paper, the author compares this pock-counting method with another method—titration by intravenous injection of chick embryos. He concludes that, although the reproducibility of titrations by intravenous injection compares very favourably with that obtained by chorio-allantoic inoculation, the former method would not be advantageous for the assay of vaccines, since it is very time-consuming and since differences in virulence might obscure comparisons between the efficacy of vaccines. PMID:14404376

  19. Candida glabrata olecranon bursitis treated with bursectomy and intravenous caspofungin.

    PubMed

    Skedros, John G; Keenan, Kendra E; Trachtenberg, Joel D

    2013-01-01

    Orthopedic surgeons are becoming more involved in the care of patients with septic arthritis and bursitis caused by yeast species. This case report involves a middle-aged immunocompromised female who developed a Candida glabrata septic olecranon bursitis that developed after she received a corticosteroid injection in the olecranon bursa for presumed aseptic bursitis. Candida (Torulopsis) glabrata is the second most frequently isolated Candida species from the bloodstream in the United States. Increased use of fluconazole and other azole antifungal agents as a prophylactic treatment for recurrent Candida albicans infections in immunocompromised individuals is one reason why there appears to be increased resistance of C. glabrata and other nonalbicans Candida (NAC) species to fluconazole. In this patient, this infection was treated with surgery (bursectomy) and intravenous caspofungin, an echinocandin. This rare infectious etiology coupled with this intravenous antifungal treatment makes this case novel among cases of olecranon bursitis caused by yeasts.

  20. Intravenous medication administration in intensive care: opportunities for technological solutions.

    PubMed

    Moss, Jacqueline; Berner, Eta; Bothe, Olaf; Rymarchuk, Irina

    2008-11-06

    Medication administration errors have been shown to be frequent and serious. Error is particularly prevalent in highly technical specialties such as critical care. The purpose of this study was to describe the characteristics of intravenous medication administration in five intensive care units. These data were used within the context of a larger study to design information system decision support in these settings. Nurses were observed during the course of their work and their intravenous medication administration process, order source, references used, calculation method, number of medications prepared simultaneously, and any interruptions occurring during the preparation and delivery phases of the administration event were recorded. In addition, chart reviews of medication administration records were completed and nurses were asked to complete an anonymous drop-box questionnaire regarding their experiences with medication administration error. The results of this study are discussed in terms of potential informatics solutions for reducing medication administration error.

  1. Symptomatic sinus bradycardia: A rare adverse effect of intravenous ondansetron

    PubMed Central

    Moazzam, Md Shahnawaz; Nasreen, Farah; Bano, Shahjahan; Amir, Syed Hussain

    2011-01-01

    Ondansetron is a serotonin receptor antagonist which has been used frequently to reduce the incidence of post-operative nausea and vomiting in laparoscopic surgery. It has become very popular drug for the prevention of post-operative nausea and vomiting due to its superiority in-terms of efficacy as well as lack of side effects and drug interactions. Although cardiovascular adverse effects of this drug are rare, we found a case of symptomatic sinus bradycardia in a 43-year-old female patient, going for laparoscopic cholecystectomy, who developed the same after she was given intravenous ondansetron in operation theater during premedication. Hence, we report this case, as the rare possibility of encountering bradycardia effect after intravenous administration of ondansetron should be born in mind. PMID:21655029

  2. Successful treatment of refractory Trichomonas vaginalis infection using intravenous metronidazole.

    PubMed

    Hawkins, Isobel; Carne, Christopher; Sonnex, Christopher; Carmichael, Andrew

    2015-08-01

    Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in a vulvo-vaginitis and altered vaginal discharge in symptomatic women. Since its introduction in the 1960 s, metronidazole has been the first-line drug for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or reinfection, although metronidazole resistance has previously been documented. Sensitivity testing is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. This case looks at a patient with refractory disease over an 18-month period, where intravenous infusion of metronidazole resulted in cure after multiple previous therapy failures. There is limited evidence to endorse the use of intravenous metronidazole, and this case report provides further support for its efficacy.

  3. Patterns of lifetime drug use among intravenous drug users.

    PubMed

    Dinwiddie, S H; Reich, T; Cloninger, C R

    1992-01-01

    To obtain a clearer description of the natural history of intravenous drug use (IVDU), 92 intravenous drug users (IVDUs), not selected through treatment or contact with the legal system, were identified. Concerning lifetime use, central nervous system (CNS) stimulants were the most common class of drug to be injected (by 72.8% of IVDUs), followed by opiates (by 50.0% of IVDUs). Mean age of onset of IVDU in this sample was 18.5 years, following initiation of alcohol use by an average of 4.6 years and cannabis use by an average of 2.1 years. Any history of IVDU in this sample indicated substantial lifetime use of illicit drugs and early onset of psychoactive substance use.

  4. Evaluation of an intravenous catheter for use in the horse.

    PubMed

    Gulick, B A; Meagher, D M

    1981-02-01

    A commercially available polyvinyl chloride intravenous catheter was studied in 9 horses for 3 to 10 days to evaluate the catheter's suitability for use in the horse, to develop a new insertion technique, and to establish a protocol for catheter care. Seven of the animals were clinically normal horses receiving parenteral nutrition; one was a horse with hypocalcemia receiving frequent intravenous injections of calcium gluconate, and one was a clinically normal horse receiving no infusions. The catheter dressings were changed every 48 hours, and an aspirate from the catheter and the catheter tip was cultured at the time of catheter removal. One catheter became infected following a break in the protocol. It was concluded that the polyvinyl catheter is suitable for use in the horse and that the proposed protocol for catheter insertion and maintenance may reduce the likelihood of complications such as catheter sepsis, thrombophlebitis, and embolism.

  5. Venipuncture and intravenous infusion access during zero-gravity flight

    NASA Technical Reports Server (NTRS)

    Krupa, Debra T.; Gosbee, John; Billica, Roger; Bechtle, Perry; Creager, Gerald J.; Boyce, Joey B.

    1991-01-01

    The purpose of this experiment is to establish the difficulty associated with securing an intravenous (IV) catheter in place in microgravity flight and the techniques applicable in training the Crew Medical Officer (CMO) for Space Station Freedom, as well as aiding in the selection of appropriate hardware and supplies for the Health Maintenance Facility (HMF). The objectives are the following: (1) to determine the difficulties associated with venipuncture in a microgravity environment; (2) to evaluate the various methods of securing an IV catheter and attached tubing for infusion with regard to the unique environment; (3) to evaluate the various materials available for securing an intravenous catheter in place; and (4) to evaluate the fluid therapy administration system when functioning in a complete system. The inflight test procedures and other aspects of the KC-135 parabolic flight test to simulate microgravity are presented.

  6. Monoclonal antibody-targeted PEGylated liposome-ICG encapsulating doxorubicin as a potential theranostic agent.

    PubMed

    Lozano, Neus; Al-Ahmady, Zahraa S; Beziere, Nicolas S; Ntziachristos, Vasilis; Kostarelos, Kostas

    2015-03-30

    Indocyanine green (ICG) is an FDA-approved, strongly photo-absorbent/fluorescent probe that has been incorporated into a clinically-relevant PEGylated liposome as a flexible optoacoustic contrast agent platform. This study describes the engineering of targeted PEGylated liposome-ICG using the anti-MUC-1 "humanized" monoclonal antibody (MoAb) hCTM01 as a tumour-specific theranostic system. We aimed to visualise non-invasively the tumour accumulation of these MoAb-targeted liposomes over time in tumour-bearing mice using multispectral optoacoustic tomography (MSOT). Preferential accumulation of targeted PEGylated liposome-ICG was studied after intravenous administration in comparison to non-targeted PEGylated liposome-ICG using both fast growing (4T1) and slow growing (HT-29) MUC-1 positive tumour models. Monitoring liposomal ICG in the tumour showed that both targeted and non-targeted liposome-ICG formulations preferentially accumulated into the tumour models studied. Rapid accumulation was observed for targeted liposomes at early time points mainly in the periphery of the tumour volume suggesting binding to available MUC-1 receptors. In contrast, non-targeted PEGylated liposomes showed accumulation at the centre of the tumour at later time points. In an attempt to take this a step further, we successfully encapsulated the anticancer drug, doxorubicin (DOX) into both targeted and non-targeted PEGylated liposome-ICG. The engineering of DOX-loaded targeted ICG liposome systems present a novel platform for combined tumour-specific therapy and diagnosis. This can open new possibilities in the design of advanced image-guided cancer therapeutics.

  7. Preparation of intravenous cholesterol tracer using current good manufacturing practices1[S

    PubMed Central

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Swaney, William P.; Ostlund, Richard E.

    2015-01-01

    Studies of human reverse cholesterol transport require intravenous infusion of cholesterol tracers. Because insoluble lipids may pose risk and because it is desirable to have consistent doses of defined composition available over many months, we investigated the manufacture of cholesterol tracer under current good manufacturing practice (CGMP) conditions appropriate for phase 1 investigation. Cholesterol tracer was prepared by sterile admixture of unlabeled cholesterol or cholesterol-d7 in ethanol with 20% Intralipid®. The resulting material was filtered through a 1.2 micron particulate filter, stored at 4°C, and tested at time 0, 1.5, 3, 6, and 9 months for sterility, pyrogenicity, autoxidation, and particle size and aggregation. The limiting factor for stability was a rise in thiobarbituric acid-reacting substances of 9.6-fold over 9 months (P < 0.01). The emulsion was stable with the Z-average intensity-weighted mean droplet diameter remaining at 60 nm over 23 months. The zeta potential (a measure of negative surface charge protecting from aggregation) was unchanged at −36.2. Rapid cholesterol pool size was 25.3 ± 1.3 g. Intravenous cholesterol tracer was stable at 4°C for 9 months postproduction. CGMP manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies. PMID:26416797

  8. Pharmacokinetics of intravenous and oral tramadol in the bald eagle (Haliaeetus leucocephalus).

    PubMed

    Souza, Marcy J; Martin-Jimenez, Tomas; Jones, Michael P; Cox, Sherry K

    2009-12-01

    Analgesia is becoming increasingly important in veterinary medicine, and little research has been performed that examined pain control in avian species. Tramadol is a relatively new drug that provides analgesia by opioid (mu), serotonin, and norepinephrine pathways, with minimal adverse effects. To determine the pharmacokinetics of tramadol and its major metabolite O-desmethyltramadol (M1) in eagles, 6 bald eagles (Haliaeetus leucocephalus) were each dosed with tramadol administered intravenously (4 mg/kg) and orally (11 mg/kg) in a crossover study. Blood was collected at various time points between 0 and 600 minutes and then analyzed with high-performance liquid chromatography to determine levels of tramadol and M1, the predominate active metabolite. The terminal half-life of tramadol after intravenous dosing was 2.46 hours. The maximum plasma concentration, time of maximum plasma concentration, and terminal half life for tramadol after oral dosing were 2156.7 ng/ml, 3.75 hours, and 3.14 hours, respec vely. In addition, the oral bioavailability was 97.9%. Although plasma concentrations of ramadol and M1 associated with analgesia in any avian species is unknown, based on the obtained data and known therapeutic levels in humans, a dosage of 5 mg/kg PO q12h is recommended for bald eagles. Pharmacodynamic studies are needed to better determine plasma levels of tramadol and M1 associated with analgesia in birds.

  9. Intravenous coronary angiography utilizing K-emission and bremsstrahlung X-rays produced by electron bombardment

    SciTech Connect

    1992-12-31

    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with synchrotron radiation at SSRL and NSLS have shown that such an intravenous angiography procedure would be possible with an intense source of monochromatic X-rays. Because of the high cost of an electron synchrotron, theoretical analysis and experiments using inanimate phantoms has been undertaken to demonstrate the feasibility of using the spectrum produced by two appropriately chosen anode materials when bombarded with electrons in the 100--500 keV energy range for angiography. By using the X-rays emitted at 120{degree} to the incident electron direction, about 20--30% of the X-ray intensity would be due to K-emission lines. Calculations using the TIGERP Monte Carlo Code, have shown that high quality angiograms of human coronary arteries should be possible with a contrast agent containing ytterbium, if an electron beam pulses of 16 kJ were used for each anode target. The experimental program supported in part by the DOE has consisted of these theoretical calculations and experiments at the Dynamitron Electron Accelerator Facility at BNL.

  10. Early effect of a single intravenous injection of ethanol on hepatic sinusoidal endothelial fenestrae in rabbits

    PubMed Central

    Jacobs, Frank; Wisse, Eddie; De Geest, Bart

    2009-01-01

    Background It has been postulated that ethanol affects hepatic sinusoidal and perisinusoidal cells. In the current experimental study, we investigated the early effect of a single intravenous dose of ethanol on the diameter of liver sinusoidal endothelial fenestrae in New Zealand White rabbits. The diameter of fenestrae in these rabbits is similar to the diameter found in humans with healthy livers. The effect of ethanol on the size of fenestrae was studied using transmission electron microscopy, because plastic embedding provides true measures for the diameter of fenestrae. Results After intravenous administration of a single dose of 0.75 g/kg, ethanol concentration peaked at 1.1 ± 0.10 g/l at ten minutes after injection. Compared to control rabbits (103 ± 1.1 nm; n = 8), the average diameter of fenestrae in ethanol-injected rabbits determined at 10 minutes after injection was significantly (p < 0.01) smaller (96 ± 2.2 nm; n = 5). Detailed analysis of distribution histograms of the diameters of fenestrae showed that the effect of ethanol was highly homogeneous. Conclusion A decrease of the diameter of fenestrae 10 minutes after ethanol administration is likely the earliest morphological alteration induced by ethanol in the liver and underscores the potential role of liver sinusoidal endothelial cells in alcoholic liver injury. PMID:19594919

  11. Effects of Intravenous Nicotine on Prepulse Inhibition in Smokers and Nonsmokers: Relationship with Familial Smoking

    PubMed Central

    Drobes, David J.; MacQueen, David A.; Blank, Melissa D.; Saladin, Michael E.; Malcolm, Robert J.

    2013-01-01

    Rationale The reinforcing properties of nicotine may be, in part, derived from its ability to enhance certain forms of cognitive processing. Several animal and human studies have shown that nicotine increases prepulse inhibition (PPI) of the startle reflex. However, it remains unclear whether these effects are related to smoking susceptibility. Objectives The current study examined the effects of intravenously delivered nicotine on PPI in smokers and nonsmokers, as well as its association with a quantitative index of familial smoking. Methods The sample consisted of 30 non-smokers and 16 smokers, who completed an initial assessment, followed on a separate day by a laboratory assessment of PPI prior to and following each of two intravenous nicotine infusions. Separate doses were used in smoker and non-smoker samples. Results Analyses indicated that both nicotine infusions acutely enhanced PPI among non-smokers, and this enhancement was positively related to the degree of smoking among first and second-degree relatives. Smokers also displayed PPI enhancement after receiving the first infusion, but this effect was unrelated to familial smoking. Conclusions These data suggest that the PPI paradigm may have utility as an endophenotype for cognitive processes which contribute to smoking risk. PMID:23624809

  12. Ultrasound Guidance as a Rescue Technique for Peripheral Intravenous Cannulation

    DTIC Science & Technology

    2006-09-14

    painful, time consuming, and may result in arterial puncture, nerve damage, and paresthes ias.5 Other routes such as central venous or venous cut down...peripherally inserted central lines-PICCS), femoral catheterizations during cardiopulmonary resuscitation, and peripheral IV catheters in difficult...techniques for gaining venous access. What to do when peripheral intravenous catheterization is not possible. J Crit 11/n. 1993;8:435-442. 2. Nee PA

  13. [Administration of intravenous sedation with midazolam by dentists is unsafe].

    PubMed

    Broers, D L M; Plat, J; de Jongh, A; Zuidgeest, T G M; Blom, H C C M; Kraaijenhagen, A E; Pieterse, C M; Bildt, M M

    2015-03-01

    In the December issue of the Nederlands Tijdschrift voor Tandheelkunde (Dutch Journal of Dentistry) in 2014, an article was devoted to the use of light sedation with midazolam by dentists. A number of dentists who are active in the area of Special Dentistry (anxiety management, care of the disabled) and a anesthesiologist offer a response to the article and argue that the administration of intravenous sedation with midazolam by dentists is unsafe.

  14. Gestation Time-Dependent Pharmacokinetics of Intravenous (+)-Methamphetamine in Rats

    PubMed Central

    White, Sarah; Laurenzana, Elizabeth; Hendrickson, Howard; Gentry, W. Brooks

    2011-01-01

    We tested the hypothesis that differences in (+)-methamphetamine (METH) disposition during late rat pregnancy could lead to increased vulnerability to acute METH effects. The disposition of a single 1 mg/kg i.v. METH dose was studied during early (gestation day 7, GD7) and late (GD21) gestation. Results showed gestation time-dependent pharmacokinetics, characterized by a significantly higher area under the METH serum concentration versus time curve and a lower clearance on GD21 (p < 0.05; total, renal, and nonrenal clearance). The terminal elimination half-life (t1/2λz) of METH and (+)-amphetamine (AMP; a pharmacologically active metabolite of METH) were not different on GD7, but by GD21, AMP t1/2λz was 37% longer than METH t1/2λz (p < 0.05). To identify the mechanism for AMP metabolite changes, intravenous AMP pharmacokinetics on GD21 were compared with AMP metabolite pharmacokinetics after intravenous METH. The intravenous AMP t1/2λz was significantly shorter than metabolite AMP t1/2λz (p < 0.05), which suggested AMP metabolite formation (not elimination) was the rate-limiting process. To understand the medical consequence of METH use during late-stage pregnancy, timed-pregnant rats received an intravenous dose of saline or METH (1, 3, or 5.6 mg/kg) on GD21, 0 to 2 days antepartum. Although one rat died and another had stillbirths at term after the 5.6-mg/kg dose, the pharmacokinetic values for all of the other animals were not significantly different. In conclusion, late-gestational clearance reductions lengthen METH exposure time, possibly increasing susceptibility to adverse effects, including death. PMID:21632964

  15. Distribution of creatinine following intravenous and oral administration to rats.

    PubMed

    Watanabe, J; Hirate, J; Iwamoto, K; Ozeki, S

    1981-05-01

    To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

  16. Gestation time-dependent pharmacokinetics of intravenous (+)-methamphetamine in rats.

    PubMed

    White, Sarah; Laurenzana, Elizabeth; Hendrickson, Howard; Gentry, W Brooks; Owens, S Michael

    2011-09-01

    We tested the hypothesis that differences in (+)-methamphetamine (METH) disposition during late rat pregnancy could lead to increased vulnerability to acute METH effects. The disposition of a single 1 mg/kg i.v. METH dose was studied during early (gestation day 7, GD7) and late (GD21) gestation. Results showed gestation time-dependent pharmacokinetics, characterized by a significantly higher area under the METH serum concentration versus time curve and a lower clearance on GD21 (p < 0.05; total, renal, and nonrenal clearance). The terminal elimination half-life (t(1/2λz)) of METH and (+)-amphetamine (AMP; a pharmacologically active metabolite of METH) were not different on GD7, but by GD21, AMP t(1/2λz) was 37% longer than METH t(1/2λz) (p < 0.05). To identify the mechanism for AMP metabolite changes, intravenous AMP pharmacokinetics on GD21 were compared with AMP metabolite pharmacokinetics after intravenous METH. The intravenous AMP t(1/2λz) was significantly shorter than metabolite AMP t(1/2λz) (p < 0.05), which suggested AMP metabolite formation (not elimination) was the rate-limiting process. To understand the medical consequence of METH use during late-stage pregnancy, timed-pregnant rats received an intravenous dose of saline or METH (1, 3, or 5.6 mg/kg) on GD21, 0 to 2 days antepartum. Although one rat died and another had stillbirths at term after the 5.6-mg/kg dose, the pharmacokinetic values for all of the other animals were not significantly different. In conclusion, late-gestational clearance reductions lengthen METH exposure time, possibly increasing susceptibility to adverse effects, including death.

  17. Neuroprotective Effects of Intravenous Anesthetics: A New Critical Perspective

    PubMed Central

    Bilotta, Federico; Stazi, Elisabetta; Zlotnik, Alexander; Gruenbaum, Shaun E.; Rosa, Giovanni

    2015-01-01

    Perioperative cerebral damage can result in various clinical sequela ranging from minor neurocognitive deficits to catastrophic neurological morbidity with permanent impairment and death. The goal of neuroprotective treatments is to reduce the clinical effects of cerebral damage through two major mechanisms: increased tolerance of neurological tissue to ischemia and changes in intra-cellular responses to energy supply deprivation. In this review, we present the clinical evidence of intravenous anesthetics on perioperative neuroprotection, and we also provide a critical perspective for future studies. The neuroprotective efficacy of the intravenous anesthetics thiopental, propofol and etomidate is unproven. Lidocaine may be neuroprotective in non-diabetic patients who have undergoing cardiac surgery with cardiopulmonary bypass (CBP) or with a 48-hour infusion, but conclusive data are lacking. There are several limitations of clinical studies that evaluate postoperative cognitive dysfunction (POCD), including difficulties in identifying patients at high-risk and a lack of consensus for defining the “gold-standard” neuropsychological testing. Although a battery of neurocognitive tests remains the primary method for diagnosing POCD, recent evidence suggests a role for novel biomarkers and neuroimaging to preemptively identify patients more susceptible to cognitive decline in the perioperative period. Current evidence, while inconclusive, suggest that intravenous anesthetics may be both neuroprotective and neurotoxic in the perioperative period. A critical analysis on data recorded from randomized control trials (RCTs) is essential in identifying patients who may benefit or be harmed by a particular anesthetic. RCTs will also contribute to defining methodologies for future studies on the neuroprotective effects of intravenous anesthetics. PMID:24669972

  18. Classification of chronic orofacial pain using an intravenous diagnostic test.

    PubMed

    Tjakkes, G-H E; De Bont, L G M; Van Wijhe, M; Stegenga, B

    2009-07-01

    The aim of this study was to evaluate the ability of a preliminary intravenous diagnostic test to classify chronic orofacial pain patients into different subgroups. Patients with chronic orofacial pain conditions that could not be unambiguously diagnosed. A retrospective evaluation of series of conducted pharmacodiagnostic tests, consisting of the consecutive intravenous administration of drugs. Visual analogue scale scores were retrieved from all patients, based on which they were classified into different responder groups. In total, 46 pain profiles were analysed. Of these, 16 patients (35%) could be classified into one or more pain categories, while 30 patients (65%) could not be classified into any pain category. The pain duration or medication use did not influence the classification. Based on the results of this retrospective study, it seems that classification into subgroups is possible after intravenous testing in a minority of clinically unclassifiable patients. In patients where there is a substantial need for additional diagnostic information, these results may be of value. Recommendations are made for further research, which should include validation in patients with known pain mechanisms.

  19. Disposition of 2-mercaptobenzimidazole in rats dosed orally or intravenously

    SciTech Connect

    El Dareer, S.M.; Kalin, J.R.; Tillery, K.F.; Hill, D.L.

    1984-01-01

    The disposition of (/sup 14/C)-labeled 2-mercaptobenzimidazole (MBI) in male Fischer-344 rats dosed orally (49 or 0.5 mg/kg) or intravenously (0.5 mg/kg) was determined. Absorption of the oral dose was evident, since, in 72 h, most of the radioactivity administered by either route appeared in the urine. Smaller amounts appeared in the feces. In 4 h, 12% of the radioactivity from an intravenous dose of 0.5 mg/kg was excreted in the bile of rats with biliary cannulas. For rats dosed intravenously, the half-life for disappearance of unchanged MBI from plasma was 125 min. In contrast, the terminal half-life for loss of radioactivity from blood was 83 h. The concentration of total radioactivity was higher in liver and kidney tissue than in blood. One of the major urinary metabolites was identified as benzimidazole, and a minor component was tentatively identified as unchanged MBI. Neither of these could be detected in bile. 8 references, 6 figures, 1 table.

  20. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration

    PubMed Central

    Jeon, Dae-Hong; Kim, Yire; Kim, Min Jeong; Cho, Hyun Seop; Bae, Eun Jin; Chang, Se-Ho; Park, Dong Jun

    2016-01-01

    Abstract Background: Proton pump inhibitors are usually safe, although serious adverse effects can occur. We report the first case of rhabdomyolysis associated with single-dose intravenous esomeprozole administration. Methods: A 45-year-old Korean male visited our emergency room because of persistent lower chest discomfort that started 10 hours before. He had been diagnosed with diabetes and coronary heart disease, but discontinued oral hypoglycemic agents 1 month earlier. He continued to take medications for coronary heart disease. There was no abnormality on an electrocardiogram or in cardiac enzymes. Initial laboratory findings did not show abnormalities for muscle enzymes. Esomeprozole 40 mg was administrated intravenously for the control of his ambiguous chest discomfort. Then, 12 hours later, he complained of abrupt severe right buttock pain. An area of tender muscle swelling 8 cm in diameter was seen on his right buttock area. Creatine kinase and lactate dehydrogenase were elevated to 40,538 and 1326 U/L, respectively. A bone scan using 20 mCi of 99mTc-hydroxymethylene diphosphonate was compatible with rhabdomyolysis. Results: His muscular symptoms, signs, and laboratory findings improved markedly with conservative management, including hydration and urine alkalinization. He is being followed in the outpatient department with no evidence of recurrence. Conclusion: We should keep in mind that single-dose intravenous administration of esomeprazole can induce rhabdomyolysis. PMID:27442680

  1. Single-dose pharmacokinetics of intravenous sulbactam in pediatric patients.

    PubMed

    Schaad, U B; Guenin, K; Straehl, P

    1986-01-01

    The pharmacokinetics of intravenously administered sulbactam were studied in 17 pediatric patients two to 14 years of age. Single doses of 12.5 or 25 mg/kg were infused over 3 min, and in previously healthy children, mean peak plasma concentrations 5 min after dosing were 71 and 163 micrograms/ml, respectively. Noncompartmental and compartmental calculations resulted in similar pharmacokinetic parameters. Linear pharmacokinetics were found in the concentration range studied. The mean terminal-phase half-life was 1.75 hr, the mean total plasma clearance was 180 ml/min per 1.73 m2, and the mean apparent volume of distribution was 340 ml/kg. Approximately 70%-80% of an intravenous dose was excreted unchanged in the urine. In children with cystic fibrosis, both total plasma clearance and apparent volume of distribution were significantly increased. The data support the intravenous administration of 12.5-25 mg of sulbactam/kg every 6 to 8 hr for assessing the adequacy of this drug as an adjunct to beta-lactam therapy for various bacterial infections in children.

  2. [National multicenter survey: the use of intravenous antimicrobial agents].

    PubMed

    Gutiérrez Zufiaurre, M N; García-Rodríguez, J A

    2006-12-01

    Infectious diseases are currently one of the major health problems worldwide. As a consequence, both nosocomial and community-acquired infections are responsible for a significant increase in workload and health costs for hospitals, particularly in Intensive Care Units (ICU), Internal Medicine and Surgery. The use of intravenous antimicrobial agents is common in hospitalized patients. In order to determine the use of antimicrobial agents and the most frequent procedures used for their administration in Spanish hospitals, a national multicenter survey was undertaken among ICU, Internal Medicine and Surgery health staff from 63 hospitals, in which data were collected on central and peripheral catheter manipulation and intravenous administration. Results showed that, in Spain, both catheter manipulation (insertion, maintenance and removal) and administration of antimicrobial agents are performed by the nursing staff following established protocols, particularly for central catheters. Moreover, the ICUs had the highest rates of catheter-bearing patients, as well as patients undergoing antimicrobial treatment, sometimes in combination. The use of intravenous antimicrobial agents in Spanish hospitals results in an increased workload for the nursing staff and higher health costs, not to mention the risk involved with the use of vascular catheters.

  3. Oral, subcutaneous, and intravenous pharmacokinetics of ondansetron in healthy cats.

    PubMed

    Quimby, J M; Lake, R C; Hansen, R J; Lunghofer, P J; Gustafson, D L

    2014-08-01

    Ondansetron is a 5-HT3 receptor antagonist that is an effective anti-emetic in cats. The purpose of this study was to evaluate the pharmacokinetics of ondansetron in healthy cats. Six cats with normal complete blood count, serum biochemistry, and urinalysis received 2 mg oral (mean 0.43 mg/kg), subcutaneous (mean 0.4 mg/kg), and intravenous (mean 0.4 mg/kg) ondansetron in a cross-over manner with a 5-day wash out. Serum was collected prior to, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18, and 24 h after administration of ondansetron. Ondansetron concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Repeated measures anova was used to compare parameters between administration routes. Bioavailability of ondansetron was 32% (oral) and 75% (subcutaneous). Calculated elimination half-life of ondansetron was 1.84 ± 0.58 h (intravenous), 1.18 ± 0.27 h (oral) and 3.17 ± 0.53 h (subcutaneous). The calculated elimination half-life of subcutaneous ondansetron was significantly longer (P < 0.05) than oral or intravenous administration. Subcutaneous administration of ondansetron to healthy cats is more bioavailable and results in a more prolonged exposure than oral administration. This information will aid management of emesis in feline patients.

  4. Intravenous atropine treatment in infantile hypertrophic pyloric stenosis

    PubMed Central

    Kawahara, H; Imura, K; Nishikawa, M; Yagi, M; Kubota, A

    2002-01-01

    Aims: To assess the efficacy of a new regimen of intravenous atropine treatment for infantile hypertrophic pyloric stenosis (IHPS) with special reference to regression of pyloric hypertrophy. Methods: Atropine was given intravenously at a dose of 0.01 mg/kg six times a day before feeding in 19 patients with IHPS diagnosed from radiographic and ultrasonographic findings. When vomiting ceased and the infants were able to ingest 150 ml/kg/day formula after stepwise increases in feeding volume, they were given 0.02 mg/kg atropine six times a day orally and the dose was decreased stepwise. Results: Of the 19 infants, 17 (89%) ceased projectile vomiting after treatment with intravenous (median seven days) and subsequent oral (median 44 days) atropine administration. The remaining two infants required surgery. No significant complications were encountered. Ultrasonography showed a significant (p < 0.05) decrease in pyloric muscle thickness, but no significant shortening of the pyloric canal after completion of the atropine treatment. The patients exhibited failure to thrive at presentation, but were thriving at 6 months of age (p < 0.01). Conclusions: This atropine therapy resulted in satisfactory clinical recovery. Pyloric muscle thickness was significantly reduced. PMID:12089130

  5. Persistent staphylococcal bacteremia in an intravenous drug abuser.

    PubMed

    Barg, N L; Supena, R B; Fekety, R

    1986-02-01

    A patient with methicillin-resistant Staphylococcus aureus bacteremia received vancomycin (MIC = 0.8 microgram/ml, MBC = 15 micrograms/ml) and heparin simultaneously through the same intravenous line to treat a septic deep venous thrombosis. Bacteremia persisted for 7 days. Bacteremia terminated when the simultaneous infusion of heparin and vancomycin through the same line was stopped. This suggested that an interaction between vancomycin and heparin may have occurred, which resulted in a reduction in vancomycin activity. To test for such an interaction, mixtures of heparin and vancomycin in various concentrations were made and tested for antimicrobial activity against the organisms in the patient. A precipitate formed at the concentrations achieved in the intravenous lines, and when the vancomycin concentrations were measured by bioassay, a 50 to 60% reduction in activity was noted. In contrast, when these solutions were prepared and mixed at microgram concentrations, a precipitate was no longer observed, and antimicrobial activity was not reduced. Heparin appeared to interact unfavorably with vancomycin at the concentrations in the intravenous lines when these drugs were administered simultaneously to patients. This may be the cause of poor therapeutic responses to vancomycin in some patients, especially those infected with tolerant organisms.

  6. Continuous intravenous epoprostenol for chronic thromboembolic pulmonary hypertension.

    PubMed

    Bresser, P; Fedullo, P F; Auger, W R; Channick, R N; Robbins, I M; Kerr, K M; Jamieson, S W; Rubin, L J

    2004-04-01

    Pathophysiological findings in chronic thromboembolic pulmonary hypertension (CTEPH) have suggested that a secondary small vessel arteriopathy may contribute to the haemodynamic impairment observed in these patients. It was hypothesised that this element of the elevated vascular resistance may be responsive to continuous intravenous epoprostenol therapy. Retrospectively, the clinical and haemodynamic responses to continuous intravenous epoprostenol were evaluated in nine CTEPH patients who subsequently underwent pulmonary thromboendarterectomy (PTE). Cardiopulmonary haemodynamics were determined prior to the initiation of epoprostenol, while on epoprostenol, prior to PTE, and after PTE. Six patients, treated for 2-26 months prior to PTE, experienced either clinical stability or improvement that was associated with a mean reduction in pulmonary vascular resistance (PVR) of 28% (median 33%, range 0-46%). Three patients, treated for 3-9 months, experienced clinical deterioration during epoprostenol administration, with a significant increase in PVR in two patients. Subsequent PTE resulted in a highly significant improvement of cardiac index, mean pulmonary artery pressure and total pulmonary resistance. To conclude, selected patients with chronic thromboembolic pulmonary hypertension may benefit clinically and haemodynamically from continuous intravenous epoprostenol treatment prior to pulmonary thromboendarterectomy. Factors predictive of a beneficial response, and whether this intervention influences either morbidity or mortality associated with pulmonary thromboendarterectomy, remain to be established.

  7. Backscattering measuring system for optimization of intravenous laser irradiation dose

    NASA Astrophysics Data System (ADS)

    Rusina, Tatyana V.; Popov, V. D.; Melnik, Ivan S.; Dets, Sergiy M.

    1996-11-01

    Intravenous laser blood irradiation as an effective method of biostimulation and physiotherapy becomes a more popular procedure. Optimal irradiation conditions for each patient are needed to be established individually. A fiber optics feedback system combined with conventional intravenous laser irradiation system was developed to control of irradiation process. The system consists of He-Ne laser, fiber optics probe and signal analyzer. Intravenous blood irradiation was performed in 7 healthy volunteers and 19 patients with different diseases. Measurements in vivo were related to in vitro blood irradiation which was performed in the same conditions with force-circulated venous blood. Comparison of temporal variations of backscattered light during all irradiation procedures has shown a strong discrepancy on optical properties of blood in patients with various health disorders since second procedure. The best cure effect was achieved when intensity of backscattered light was constant during at least five minutes. As a result, the optical irradiation does was considered to be equal 20 minutes' exposure of 3 mW He-Ne laser light at the end of fourth procedure.

  8. Attenuation of Hemodynamic Response to Skull Pin Head Holder Insertion: Intravenous Clonidine versus Intravenous Lignocaine Infusion

    PubMed Central

    Nanjundaswamy, Nethra H.; Marulasiddappa, Vinay

    2017-01-01

    Background: Insertion of skull pin induces a significant increase in heart rate (HR), blood pressure (BP) and intracranial pressure. Alpha 2 agonist clonidine and intravenous (i.v.) lignocaine are effective in attenuating stress response. Local infiltration of pin site and scalp block with lignocaine are commonly used techniques for prevention of hemodynamic response to skull pin insertion. We compared the effectiveness of i.v. clonidine infusion and i.v. lignocaine infusion in suppressing the hemodynamic response to skull pin head holder insertion. Designs: Randomized double blind study conducted with sample size - sixty patients, divided into two groups: Group C (n = 30) - clonidine i.v. dose 2 μg/kg; Group L (n = 30) - lignocaine i.v. dose 1.5 mg/kg. Materials and Methods: All patients posted for elective craniotomy belonging to American Society of Anesthesiologists (ASA) 1 and 2, age group 18–70 were included in the study. ASA 3, 4; difficult airway; hypertensives; allergy to study drugs; ischemic heart disease; and arteriovenous malformations were excluded. Study drugs were administered 10 min prior to induction in 10 ml syringes with infusion pump over 10 min. Standard anesthesia protocol followed. HR, noninvasive BP, mean arterial pressure (MAP), and IBP were recorded at baseline (BL), after study drug (AD), 1 min after intubation (AI), 1 min prior to pin insertion -pre pin (PP), and 5 min after pin insertion (AP). Analysis: Descriptive and inferential statistical analysis – Student's t- and Chi-square/Fisher exact test were used (SAS 9.2, SPSS 15.0) P value described as *moderately significant (P value: 0.01 < P ≤ 0.05) **strongly significant (P value: P ≤ 0.01). Results: Groups were matched with respect to age (P = 0.7), gender distribution (P = 0.6), and weight (P = 0.67) There was no difference in BL HR in two groups. Significant difference in HR was noted after intubation P < 0.031 and pin insertion P < 0.001 stages with lower HR in Group C (76

  9. Intravenous medication safety and smart infusion systems: lessons learned and future opportunities.

    PubMed

    Keohane, Carol A; Hayes, Judy; Saniuk, Catherine; Rothschild, Jeffrey M; Bates, David W

    2005-01-01

    The Institute of Medicine report To Err Is Human: Building a Safe Health System greatly increased national awareness of the need to improve patient safety in general and medication safety in particular. Infusion-related errors are associated with the greatest risk of harm, and "smart" (computerized) infusion systems are currently available that can avert high-risk errors and provide previously unavailable data for continuous quality improvement (CQI) efforts. As healthcare organizations consider how to invest scarce dollars, infusion nurses have a key role to play in assessing need, evaluating technology, and selecting and implementing specific products. This article reviews the need to improve intravenous medication safety. It describes smart infusion systems and the results they have achieved. Finally, it details the lessons learned and the opportunities identified through the use of smart infusion technology at Brigham and Women's Hospital in Boston, Massachusetts.

  10. Intravenous Foscarnet With Topical Cidofovir for Chronic Refractory Genital Herpes in a Patient With AIDS.

    PubMed

    Usoro, Agnes; Batts, Alfreda; Sarria, Juan C

    2015-01-01

    Few case reports have documented the use of topical cidofovir for refractory genital herpes simplex virus (HSV) ulcers in human immunodeficiency virus (HIV) infected patients. This drug formulation lacks a standardized concentration or even a procedural outline as to how it should be compounded. We aim to discuss the utilization of topical cidofovir in addition to presenting a procedural means of compounding it for treatment of refractory genital HSV ulcers. Our patient completed 21 days of intravenous foscarnet and 13 days of topical cidofovir with clinical improvement in the penile and scrotal ulcers. Genital herpes is a concern in patients with HIV because it generally manifests as a persistent infection. Physicians should be aware that when patients fail to respond to the conventional treatment regimens for genital HSV in a timely manner, other options are available, such as topical cidofovir as an adjuvant to systemic antivirals.

  11. Efficacy of Intravenous Infusion of Acetaminophen for Intrapartum Analgesia

    PubMed Central

    Zutshi, Vijay; Rani, Kumari Usha; Patel, Madhumita

    2016-01-01

    Introduction The intensity of pain experienced by women in labour, has been found to affect the progress of labour, foetal well-being and maternal psychology. Adverse effects associated with commonly used opioids for providing intrapartum analgesia have created a need for an alternative non-opioid drug. Aim To evaluate the efficacy of an intravenous infusion of 1000 mg of acetaminophen as an intrapartum analgesic. Materials and Methods The present prospective single-centre, single blind, placebo-controlled randomized interventional study was conducted in Department of Obstetrics and Gynaecology in Vardhaman Mahavir Medical College & Safdarjung Hospital over a period of six months from September 2014 to March 2015. After receiving the ethical clearance and written informed consent. The first 200 consecutive parturients fulfilling the inclusion criteria were recruited into the study. Women were then randomised to receive either intravenous 1000 mg (100ml) of acetaminophen (Group A, n=100) or 100 ml normal saline (Group B, n=100). Primary outcome assessed was effectiveness of acetaminophen to provide an adequate amount of analgesia, as measured by a change in Visual Analogue Scale (VAS) pain intensity score at various times after drug administration. Secondary outcomes measured were duration of labour, need for additional rescue analgesia and presence of adverse maternal or foetal effect. Results There was pain reduction at 1 and 2 hours in both groups (p<0.001). However, it was more significant in the acetaminophen group, especially at 1 hour. Duration of labour was shortened in both the groups, without any maternal and foetal adverse effects. Conclusion Intravenous acetaminophen is an efficacious non-opioid drug for relieving labour pain without any significant maternal and foetal adverse effects. PMID:27656511

  12. Intravenous dipyridamole thallium-201 SPECT imaging methodology, applications, and interpretations

    SciTech Connect

    Rockett, J.F.; Magill, H.L.; Loveless, V.S.; Murray, G.L. )

    1990-10-01

    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.

  13. Intravenous methylphenidate abuse. Prototype for prescription drug abuse.

    PubMed

    Parran, T V; Jasinski, D R

    1991-04-01

    Data are presented from a case series of 22 patients who abused methylphenidate hydrochloride (Ritalin-SR). The abuse pattern and symptoms of toxicity were similar to that seen with cocaine hydrochloride and amphetamine sulfate addiction; yet, the morbidity and mortality seen in this case series were greater than usual for a group of patients involved in intravenous drug abuse. We describe the characteristics of the methylphenidate abuse syndrome in terms of the pharmacology of methylphenidate, the constituents of the Ritalin-SR preparation, and the disease of chemical dependence. We propose solutions to the problem of methylphenidate abuse.

  14. [Intravenous methyl iodide poisoning--detoxification using hemoperfusion].

    PubMed

    Robertz-Vaupel, G M; Bierl, R; von Unruh, G

    1991-02-01

    A 19-year-old patient intending to commit suicide gave himself an intravenous injection of about 14 g methyliodide. The patient was admitted to our hospital in a state of somnolence and agitation followed by a cerebral convulsion and severe hypotension. The serum concentration of methyl iodide was measured by mass spectroscopy. In addition to an antidote therapy with acetylcysteine, haemoperfusion was performed followed by a remarkable decrease of the methyliodide concentration. The patient survived this severe intoxication and was discharged from the hospital after a week.

  15. Toxicity with intravenous injection of naphtha in man

    SciTech Connect

    Vaziri, N.D.; Smith, P.J.; Wilson, A.

    1980-01-01

    Intravenous injection of charcoal lighter fluid (naphtha) in a suicidal attempt led to development of severe hemorrhagic pneumonitis in a 40-year-old individual. Presenting symptoms consisted of pleuritic chest pain, epigastric discomfort, and dyspnea; they appeared within 2 hours after injection. Development of roentgenographic changes lagged behind the clinical symptoms by several hours. Fever and leukocytosis were present despite the absence of demonstrable superimposed bacterial infection. The pathology seemed exclusively confined to the pulmonary system with no clinical or laboratory evidence of extrapulmonary involvement. Repeated clinical, radiographic, and pulmonary function evaluations over an 18-month follow-up period have shown complete resolution of pulmonary lesions without residual abnormalities.

  16. Acute toxicity of nickel nanoparticles in rats after intravenous injection

    PubMed Central

    Magaye, Ruth R; Yue, Xia; Zou, Baobo; Shi, Hongbo; Yu, Hongsheng; Liu, Kui; Lin, Xialu; Xu, Jin; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

    2014-01-01

    This study was carried out to add scientific data in regard to the use of metallic nanoparticles in nanomedicine. The acute toxicity of nickel (Ni) nanoparticles (50 nm), intravenously injected through the dorsal penile vein of Sprague Dawley rats was evaluated in this study. Fourteen days after injection, Ni nanoparticles induced liver and spleen injury, lung inflammation, and caused cardiac toxicity. These results indicate that precautionary measures should be taken with regard to the use of Ni nanoparticles or Ni compounds in nanomedicine. PMID:24648736

  17. Pharmacokinetics as applied to total intravenous anaesthesia. Practical implications.

    PubMed

    Schüttler, J; Schwilden, H; Stoekel, H

    1983-07-01

    In six patients undergoing gynaecological surgery computer assisted total intravenous anaesthesia (CATIA) was performed using etomidate and alfentanil. Constant plasma levels of etomidate (0.3 microgram/ml) from the very beginning onwards were achieved using the so called B.E.T. infusion scheme. Alfentanil plasma concentrations of 0.45 microgram/ml were maintained by the same infusion scheme beginning with skin incision until 20 minutes prior to the end of surgery. The proposed concept of CATIA provided an adequate analgesic and hypnotic effect during anaesthesia for abdominal surgery with a recovery period of short duration.

  18. The immediate effects of intravenous specific nutrients on EEG sleep.

    PubMed

    Lacey, J H; Stanley, P; Hartmann, M; Koval, J; Crisp, A H

    1978-03-01

    This study examined the immediate influence of intravenous amino acids and glucose on sleep as measured by all-night EEG recording. The study on 9 normal female subjects was of a latin-square design. Slow wave sleep (SWS) was increased by both solutions whilst dream sleep (REM) was decreased by amino acids and increased by glucose. Total sleep time was not affected. Subjective feelings as to restlessness, quality and depth of sleep under the impact of the various solutions were gathered. The work further elucidates the effect of nutrition on sleep and supports certain theories as to the function of the main sleep component.

  19. Cholescintigraphy in acute cholecystitis: use of intravenous morphine

    SciTech Connect

    Choy, D.; Shi, E.C.; McLean, R.G.; Hoschl, R.; Murray, I.P.C.; Ham, J.M.

    1984-04-01

    Conventional cholescintigraphy (60 patients) and a modified protocol (59 patients) were compared in 74 females and 45 males with acute cholecystitis. In the modified protocol, intravenous morphine was administered whenever the gallbladder was not seen 40 minutes after injection of Tc-99m-pyroxylidene-glutamate. Accuracy was 98% with morphine, compared with 88% for the conventional protocol; specificity improved from 83% to 100% with no loss of sensitivity. Low doses of morphine are well tolerated and can result in a highly accurate diagnosis of acute cholecystitis without the need for delayed imaging.

  20. Intravenous Use of Cephradine and Cefazolin Against Serious Infections

    PubMed Central

    Caloza, Dionisio L.; Semar, Richard W.; Bernfeld, Gerald E.

    1979-01-01

    The relative efficacy and safety of cephradine and cefazolin were compared in 180 patients with a variety of serious infections caused by susceptible organisms. The patients were randomly assigned to one of two groups of 90 patients each. Most patients received 2 to 4 g per day, administered by intravenous injection in four equally divided doses, for a minimum of 4 days. Based on the clinical and microbiological results, the two cephalosporins were found to be comparable in therapeutic effectiveness. Toxicity was not a problem with either drug. PMID:426499

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

    NASA Astrophysics Data System (ADS)

    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.

  2. [Acute water intoxication as complication of intravenous urography].

    PubMed

    López Del Val, T; Del Olmo, D; Diago, J; Alcazar, V; Hernández, E; Vázquez, C

    2001-05-01

    Physiologically, two complementary mechanisms regulate plasma osmolality: antduretic hormone ADH) and thirst. ADH release s supressed, thirst s inhbted and renal water loss occurs when plasma osmolality below a threshold level. The rise in plasma osmolalty causes ADH release, stimulation of thirst and water intake. Acute water intoxication is exceptional in patients without a chronic psychiatric disease. Herein, we describe a case of acute water intoxication in a previously healthy patient, after making an intravenous urography. The excessive water intake and the impossibility of renal water loss because of streee-induced ADH release originated t. Only nine cases have been previously described; almost they all were women preparing for diagnostic procedures.

  3. [Acute psychiatric symptoms during methylphenidate intravenous injections: A case report].

    PubMed

    Vérité, Fabrice; Micallef, Joëlle

    2016-11-24

    We report the case of a 32-year-old man who developed acute psychiatric disorders after repeated intravenous injections of methylphenidate. The behavioural disorders with extreme psychomotor restlessness and delirious syndrome have resolved within 24hours. The available data highlight the fact that the prescriptions of methylphenidate, an amphetamine-like substance, are constantly increasing in Europe and Northern America. The potential of abuse and addiction to this drug, which is growingly misused, is now clearly established. The medical professionals should be cautious and attentive to the risk of misuse of this drug.

  4. [Exfoliative dermatitis as a side effect of intravenous immunoglobulin treatment].

    PubMed

    Markvardsen, Lars Høj; Jakobsen, Johannes

    2011-10-24

    Three patients with immune-mediated polyneuropathies developed rash, eczema, whole body scaling, vesicles in hands and loss of hair a few days after infusion of large doses of intravenous immunoglobulin (IVIG). The condition was diagnosed as exfoliative dermatitis. Two out of three patients were afterwards treated with low doses of IVIG slowly increased over a year given under the protection of oral steroids. Our findings indicate that exfoliative dermatitis can be provoked by IVIG treatment, and that the treatment can be reinstalled by slowly increasing the IVIG dose under steroid cover.

  5. [Intravenous drop of calcium gluconate for phosphorus burns].

    PubMed

    Hu, A J

    1993-07-01

    20 patients with phosphor burn (TBSA 2%-75%) were cured by i.v. drop of calcium gluconate combined with other therapies including eschar conservation. Our experimental data showed that dogs with burn by spreading 85% phosphoric acid and napalm locally increased the level of plasma phosphorus and pathological damages to the heart, lung, kidney and etc were similar to those previously reported phosphorus burns. Intravenous drop of calcium gluconate after phosphate burn reduced the level of plasma phosphorus to normal rapidly and lessened the visceral damages. We consider that i.v. drop of calcium gluconate can accelerate the elimination of phosphorus, and prevent phosphorus poisoning after phosphorus burns.

  6. Fluoropolymer-Based Emulsions for the Intravenous Delivery of Sevoflurane

    PubMed Central

    Fast, Jonathan P.; Perkins, Mark G.; Pearce, Robert A.; Waters, Ralph M.; Mecozzi, Sandro

    2009-01-01

    Background The intravenous delivery of halogenated volatile anesthetics has been previously achieved using phospholipid-stabilized emulsions, e.g. Intralipid. However, fluorinated volatile anesthetics, such as sevoflurane, are partially fluorophilic and do not mix well with classic non-fluorinated lipids. This effect limits the maximum amount of sevoflurane that can be stably emulsified in Intralipid to 3.5% v/v. This is a significant limitation to the potential clinical use of Intralipid-based emulsions. Methods The authors prepared a 20% v/v sevoflurane emulsion using a novel fluorinated surfactant and tested its effectiveness and therapeutic index by administering it to male Sprague-Dawley rats via intravenous injection into the jugular vein. The median effective dose to induce anesthesia (ED50), median lethal dose (LD50), and therapeutic index (LD50 / ED50) were determined. Anesthesia was measured by loss of the forepaw righting reflex. Results The ED50 and LD50 values were found to be 0.41 and 1.05 mL emulsion / kg body weight, respectively. These lead to a therapeutic index of 2.6, which compares favorably to previously determined values of emulsified isoflurane, as well as values for propofol and thiopental. Conclusions A novel semi-fluorinated surfactant was able to considerably increase the maximum amount of stably emulsified sevoflurane compared to Intralipid. These formulations can be used to rapidly induce anesthesia with bolus dosing from which recovery is smooth and rapid. PMID:18813044

  7. [Intravenous amiodarone in the therapy of paroxysmal supraventricular tachycardias].

    PubMed

    Storelli, A; Andriulo, C; Chisena, A; De Giorgi, M; De Giorgio, N A; Gallone, V; Guadalupi, M; Lupis, O; Nadovezza, S; Tarentini, A

    1985-03-01

    The Authors evaluated the effectiveness and the tolerance of intravenous Amiodarone in 50 cases of recent onset paroxysmal supraventricular tachyarrhythmias. Fifty consecutive patients, aged 17 to 84 (mean 52 years), presenting with paroxysmal supraventricular tachycardia (PSVT, 33 cases) or atrial flutter (11 cases) or atrial fibrillation (6 cases), were given 300 mg of Amiodarone intravenously within 2 min, followed in 4 patients by 150 mg after 15 min. All patients were monitored for 1 hour; ECG and blood pressure were recorded at fixed times. Within 15 min sinus rhythm was restored in 88% of PSVT, in 27% of atrial flutter and in 17% of atrial fibrillation cases; the other cases of atrial flutter and fibrillation always showed a 48-81% reduction of the average heart rate within 15 min. We have evidenced neither significant modifications of blood pressure and ECG parameters (P-Q, QRS and Q-T duration) nor particular side effects, except for 2 cases in which brief hot flushes were reported. The Authors believe Amiodarone to be an effective and well tolerated drug for the above mentioned arrhythmias, particularly promptly acting in PSVT cases, in whom sinus rhythm was restored within 15 min in 88% and within 1 hour in 100% of the cases.

  8. Intravenous pamidronate in the treatment of severe idiopathic infantile hypercalcemia.

    PubMed

    Skalova, Sylva; Cerna, Lucie; Bayer, Milan; Kutilek, Stepan; Konrad, Martin; Schlingmann, Karl-Peter

    2013-03-01

    Idiopathic infantile hypercalcemia (IIH) is a rare disorder caused by CYP24A1 loss-of-function mutation, resulting in impaired degradation of 1,25-dihydroxyvitamin D3. Pamidronate, an intravenously administered bisphosphonate, which is a potent inhibitor of bone resorption, has been reported only once for treatment IIH. We present a case of a previously healthy 5-month-old boy with IIH, where calcemia peaked to 5 mmol/L. Treatment with methylprednisone and furosemide had only minor effects; therefore, 2 intravenous infusions of pamidronate (0.6 mg/kg per dose) corrected the serum calcium level to 2.95 mmol/L. Furthermore, CYP24A1 homozygous mutation p.R396W (c.1186c>t) was identified in this patient, confirming the clinical diagnosis of IIH. In conclusion, IIH has a favorable outcome once properly detected and appropriately treated. Pamidronate has a beneficial effect in those patients with IIH where glucocorticoids and furosemide fail to meet the expectations.  

  9. Comparing Intravenous Insertion Instructional Methods with Haptic Simulators

    PubMed Central

    Malecha, Ann

    2017-01-01

    Objective. The objective of this review was to compare traditional intravenous (IV) insertion instructional methods with the use of haptic IV simulators. Design. An integrative research design was used to analyze the current literature. Data Sources. A search was conducted using key words intravenous (IV) insertion or cannulation or venipuncture and simulation from 2000 to 2015 in the English language. The databases included Academic Search Complete, CINAHL Complete, Education Resource Information Center, and Medline. Review Methods. Whittemore and Knafl's (2005) strategies were used to critique the articles for themes and similarities. Results. Comparisons of outcomes between traditional IV instructional methods and the use of haptic IV simulators continue to show various results. Positive results indicate that the use of the haptic IV simulator decreases both band constriction and total procedure time. While students are satisfied with practicing on the haptic simulators, they still desire faculty involvement. Conclusion. Combining the haptic IV simulator with practical experience on the IV arm may be the best practice for learning IV insertion. Research employing active learning strategies while using a haptic IV simulator during the learning process may reduce cost and faculty time. PMID:28250987

  10. Comparing Intravenous Insertion Instructional Methods with Haptic Simulators.

    PubMed

    McWilliams, Lenora A; Malecha, Ann

    2017-01-01

    Objective. The objective of this review was to compare traditional intravenous (IV) insertion instructional methods with the use of haptic IV simulators. Design. An integrative research design was used to analyze the current literature. Data Sources. A search was conducted using key words intravenous (IV) insertion or cannulation or venipuncture and simulation from 2000 to 2015 in the English language. The databases included Academic Search Complete, CINAHL Complete, Education Resource Information Center, and Medline. Review Methods. Whittemore and Knafl's (2005) strategies were used to critique the articles for themes and similarities. Results. Comparisons of outcomes between traditional IV instructional methods and the use of haptic IV simulators continue to show various results. Positive results indicate that the use of the haptic IV simulator decreases both band constriction and total procedure time. While students are satisfied with practicing on the haptic simulators, they still desire faculty involvement. Conclusion. Combining the haptic IV simulator with practical experience on the IV arm may be the best practice for learning IV insertion. Research employing active learning strategies while using a haptic IV simulator during the learning process may reduce cost and faculty time.

  11. Individual predictors of the subjective effects of intravenous cocaine.

    PubMed

    Grasing, Kenneth; Mathur, Deepan; Newton, Thomas F; Desouza, Cherilyn

    2013-08-15

    The subjective and reinforcing effects of addictive substances can vary greatly between individuals. This study compared the relative contributions of baseline drug use, craving, stressful life events, and social factors in determining the subjective effects of cocaine in individual participants. Twelve veterans meeting criteria for cocaine dependence were evaluated in a laboratory setting. Self-report of the subjective effects of intravenous cocaine was recorded following single- and double-blind, placebo-controlled injections. Increased positive subjective effects of cocaine, including drug-induced 'good' effects and the value of intravenous injections, were most strongly correlated with greater family and social dysfunction measured through the Addiction Severity Index (ASI). Social dysfunction was the strongest predictor of cocaine-induced euphoria, accounting for approximately one-half of its variability. Participants who were dissatisfied with their current marital status reported almost no 'bad' effects of cocaine but instead reported increased drug-induced 'high', euphoria, and injection value. Although further research is required to determine the generalizability of this association, our findings are parallel to recent preclinical results showing that social interaction can attenuate psychostimulant reward. Effects of substance abuse treatment that rely on improved social function may be mediated through changes in the brain's reinforcement system that modify the rewarding effects of cocaine.

  12. Intravenous versus topical tranexamic acid in primary total hip replacement

    PubMed Central

    Zhang, Pei; Liang, Yuan; Chen, Pengtao; Fang, Yongchao; He, Jinshan; Wang, Jingcheng

    2016-01-01

    Abstract Background: As the prevalence of total hip arthroplasty (THA) is increasing, it is usually associated with considerable blood loss. Tranexamic acid (TXA) has been reported to reduce perioperative blood loss in hip joint arthroplasty. But the best route of TXA administration continues to be controversial. So, we conducted a meta-analysis that integrated all data from the 7 included trials to compare the effectiveness and safety of topical and intravenous TXA administration in primary THA. The endpoints assessed in this meta-analysis include the comparisons of total blood loss, postoperative hemoglobin decline, transfusion rates, the incidence rate of deep vein thrombosis (DVT), pulmonary embolisms (PE), and wound infection. Methods: Literature searches of PubMed, EMBASE, the Cochrane Library, the Chinese Biomedical Literature database, the CNKI database, and Wan Fang Data were performed up to August 30, 2016. Randomized controlled trials (RCTs) were included in our meta-analysis if they compared the efficiency and safety of intravenous versus topical administration of TXA in patients who underwent primary THA. The endpoints included the comparisons of total blood loss, postoperative hemoglobin decline, transfusion rates, the incidence rate of DVT, PE, and wound infection. A meta-analysis was performed following the guidelines of the Cochrane Reviewer's Handbook and the PRISMA statement. The pooling of data was carried out by using RevMan 5.3, Denmark. Results: Seven RCTs involving 964 patients met the inclusion criteria. Our meta-analysis indicated that there were no significant differences in the 2 groups in terms of total blood loss ([mean difference (MD) = −14.74, 95% confidence interval (CI): −89.21 to 59.74, P = 0.7], transfusion rates [RD = −0.02, 95% CI: −0.05 to 0.02, P = 0.39]; no significant differences were found regarding the incidence of adverse effects such as deep venous thrombosis [DVT] [RD = 0.00, 95% CI: −0

  13. Safety, Tolerability, and Pharmacokinetics of Intravenous Nemonoxacin in Healthy Chinese Volunteers

    PubMed Central

    Cao, Guo-ying; Zhang, Ying-yuan; Guo, Bei-ning; Yu, Ji-cheng; Wu, Xiao-jie; Chen, Yuan-cheng; Wu, Ju-Fang; Shi, Yao-guo

    2014-01-01

    Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent broad-spectrum activity against Gram-positive, Gram-negative, and atypical pathogens, including vancomycin-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant MRSA, quinolone-resistant Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, and erythromycin-resistant S. pneumoniae. This first-in-human study was aimed at assessing the safety, tolerability, and pharmacokinetic properties of intravenous nemonoxacin in healthy Chinese volunteers. The study comprised a randomized, double-blind, placebo-controlled, dose escalating safety and tolerability study in 92 subjects and a randomized, single-dose, open-label, 3-period Latin-square crossover pharmacokinetic study in 12 subjects. The study revealed that nemonoxacin infusion was well tolerated up to the maximum dose of 1,250 mg, and the acceptable infusion rates ranged from 0.42 to 5.56 mg/min. Drug-related adverse events (AEs) were mild, transient, and confined to local irritation at the injection site. The pharmacokinetic study revealed that after the administration of 250, 500, and 750 mg of intravenous nemonoxacin, the maximum plasma drug concentration (Cmax) values were 4.826 μg/ml, 7.152 μg/ml, and 11.029 μg/ml, respectively. The corresponding values for the area under the concentration-time curve from 0 to 72 hours (AUC0–72 h) were 17.05 μg · h/ml, 39.30 μg · h/ml, and 61.98 μg · h/ml. The mean elimination half-life (t1/2) was 11 h, and the mean cumulative drug excretion rate within 72 h ranged from 64.93% to 77.17%. Volunteers treated with 250 to 750 mg nemonoxacin exhibited a linear dose-response relationship between the AUC0–72 h and AUC0–∞. These findings provide further support for the safety, tolerability, and pharmacokinetic properties of intravenous nemonoxacin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01944774.) PMID:25092690

  14. Use of an intravenous microdose of 14C-labeled drug and accelerator mass spectrometry to measure absolute oral bioavailability in dogs; cross-comparison of assay methods by accelerator mass spectrometry and liquid chromatography-tandem mass spectrometry.

    PubMed

    Miyaji, Yoshihiro; Ishizuka, Tomoko; Kawai, Kenji; Hamabe, Yoshimi; Miyaoka, Teiji; Oh-hara, Toshinari; Ikeda, Toshihiko; Kurihara, Atsushi

    2009-01-01

    A technique utilizing simultaneous intravenous microdosing of (14)C-labeled drug with oral dosing of non-labeled drug for measurement of absolute bioavailability was evaluated using R-142086 in male dogs. Plasma concentrations of R-142086 were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and those of (14)C-R-142086 were measured by accelerator mass spectrometry (AMS). The absence of metabolites in the plasma and urine was confirmed by a single radioactive peak of the parent compound in the chromatogram after intravenous microdosing of (14)C-R-142086 (1.5 microg/kg). Although plasma concentrations of R-142086 determined by LC-MS/MS were approximately 20% higher than those of (14)C-R-142086 as determined by AMS, there was excellent correlation (r=0.994) between both concentrations after intravenous dosing of (14)C-R-142086 (0.3 mg/kg). The oral bioavailability of R-142086 at 1 mg/kg obtained by simultaneous intravenous microdosing of (14)C-R-142086 was 16.1%, this being slightly higher than the value (12.5%) obtained by separate intravenous dosing of R-142086 (0.3 mg/kg). In conclusion, on utilizing simultaneous intravenous microdosing of (14)C-labeled drug in conjunction with AMS analysis, absolute bioavailability could be approximately measured in dogs, but without total accuracy. Bioavailability in humans may possibly be approximately measured at an earlier stage and at a lower cost.

  15. Long-term outcome of lung transplantation in previous intravenous drug users with talc lung granulomatosis.

    PubMed

    Weinkauf, J G; Puttagunta, L; Nador, R; Jackson, K; LaBranche, K; Kapasi, A; Mullen, J; Modry, D L; Stewart, K C; Thakrar, M; Doucette, K; Lien, D C

    2013-01-01

    Talc lung granulomatosis results from the intravenous use of medication intended for oral use. Talc (magnesium silicate) acts as filler in some oral medications; when injected intravenously, it deposits in the lungs leading to airflow obstruction and impaired gas exchange. Allocation of donor lungs to previous intravenous drug users is controversial. After a careful selection process, 19 patients with talc lung granulomatosis have received lung allografts in our program. Long-term survival for these patients is excellent and our results suggest the previous use of intravenous drugs should not necessarily preclude lung transplantation.

  16. Intravenous azithromycin as salvage therapy in a patient with Legionnaire's disease

    PubMed Central

    Dorrell, L; Fulton, B; Ong, E L C

    1994-01-01

    A patient with proven Legionnaire's disease is described whose clinical condition improved with intravenous azithromycin after failure to respond to treatment with erythromycin and rifampicin. Images PMID:8016806

  17. Titration of intravenous synthetic oxytocin post vaginal birth following induction or augmentation.

    PubMed

    Lewis, Lucy; Hauck, Yvonne L; Pemberton, Alissa; Crichton, Caroline; Conwell, Marion

    2016-10-01

    Evidence exists for titration of intravenous oxytocin during induction and augmentation, whereas no evidence was identified for titration of intravenous oxytocin following vaginal birth, where management excluded oxytocin for postpartum haemorrhage (PPH). This retrospective cohort study explored this issue through patient case notes and computerised perinatal data. Analysis included 335 women comparing induction (n = 226, 67%) to augmentation (n = 109, 33%). The two groups differed in terms of: parity; oxytocin dosage; length of time on intravenous oxytocin; and the length of first and second stage labour. They had similar rates of PPH and titration of intravenous oxytocin following birth was rarely recorded.

  18. A review of intravenous minocycline for treatment of multidrug-resistant Acinetobacter infections.

    PubMed

    Ritchie, David J; Garavaglia-Wilson, Alexandria

    2014-12-01

    Options for treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections are extremely limited. Minocycline intravenous is active against many MDR strains of Acinetobacter, and Clinical and Laboratory Standards Institute breakpoints exist to guide interpretation of minocycline susceptibility results with Acinetobacter. In addition, minocycline intravenous holds a US Food and Drug Administration indication for treatment of infections caused by Acinetobacter. There is an accumulating amount of literature reporting successful use of minocycline intravenous for treatment of serious MDR Acinetobacter infections, particularly for nosocomial pneumonia. These results, coupled with the generally favorable tolerability of minocycline intravenous, support its use as a viable therapeutic option for treatment of MDR Acinetobacter infections.

  19. Evaluation of the serotonin receptor blocker methiothepin in broilers injected intravenously with lipopolysaccharide and microparticles.

    PubMed

    Chapman, M E; Wideman, R F

    2006-12-01

    There has been considerable interest in the role of serotonin (5-hydroxytryptamine, 5-HT) in the pathogenesis of pulmonary hypertension due to episodes of primary pulmonary hypertension in humans linked to serotoninergic appetite-suppressant drugs. In this study, we investigated the effect of 5-HT on the development of pulmonary hypertension induced by injecting bacterial lipopolysaccharide (LPS; endotoxin) and cellulose microparticles intravenously, using the nonselective 5-HT(1/2)receptor, antagonist methiothepin. In Experiment 1, broilers selected for ascites susceptibility or resistance under conditions of hypobaric hypoxia were treated with methiothepin or saline, followed by injection of LPS, while recording pulmonary arterial pressure (PAP). In Experiment 2 ascites-susceptible broilers were treated with methiothepin or saline, followed by injection of cellulose microparticles, while recording PAP. In Experiment 3, an i.v. microparticle injection dose shown to cause 50% mortality was injected into ascites-susceptible and ascites-resistant broilers after methiothepin or saline treatment. Injecting methiothepin reduced PAP below baseline values in ascites-susceptible and ascites-resistant broilers, suggesting a role for 5-HT in maintaining the basal tone of the pulmonary vasculature in broilers. Injecting microparticles into the wing vein had no affect on the PAP in the broilers treated with methiothepin, suggesting that 5-HT is an important mediator in the pulmonary hypertensive response of broilers to microparticles. Furthermore, injecting an 50% lethal dose of microparticles into ascites-susceptible and ascites-resistant broilers pretreated with methiothepin resulted in reduced mortality. Serotonin appears to play a less prominent role in the pulmonary hypertensive response of broilers to intravenously injected LPS, indicating that other mediators within the innate response to inflammatory stimuli may also be involved. These results are consistent with our

  20. Evidence for opponent-process actions of intravenous cocaine and cocaethylene.

    PubMed

    Knackstedt, Lori A; Samimi, Max M; Ettenberg, Aaron

    2002-07-01

    The affective response to cocaine (COC) has been suggested to follow a time-course and pattern that adheres to the prediction of opponent-process models of drug actions. While the initial impact of the drug is positive, within a few minutes that effect wanes and is replaced by an aversive state characterized by anxiety and drug craving. We have demonstrated this phenomenon in animals by showing that rats prefer distinctive environments associated with the immediate effects of intravenous COC (1.0 mg/kg) but avoid environments associated with the state present 15-min postinjection. Human addicts have reported taking ethanol with their COC as a means of attenuating the negative aftereffects of COC administration. The combination of ethanol and COC results in the production of cocaethylene (CE), a metabolite of COC having psychostimulant properties. The current study was devised to assess whether the immediate and delayed affective responses to CE might account for the self-medication strategy of COC addicts pretreating themselves with ethanol. Rats developed conditioned place preferences for environments paired with the immediate effects of a 1.44-mg/kg intravenous dose of CE (equimolar to a 1.0-mg/kg dose of COC). While no aversive effects were observed at 0, 5, or 15 min postinjection, reliable place avoidance was detected for an environment paired with the internal state present 30-min post-CE. These data are consistent with the view that the development of CE may account for efficacy of ethanol to delay and weaken the aversive aftereffects of COC.

  1. An HPLC-UV method for determining plasma dimethylacetamide concentrations in patients receiving intravenous busulfan.

    PubMed

    Cendana, Mildred; Lee, Samiuela; Upadhyay, Parth J; Byrne, Jennifer A; Shaw, Peter J; Earl, John; Nath, Christa E

    2016-12-07

    Dimethylacetamide (DMA) is a solvent used in the preparation of intravenous busulfan, an alkylating agent used in blood or marrow transplantation. DMA may contribute to hepatic toxicity, so it is important to monitor its clearance. The aim of this study was to develop an HPLC-UV assay for measurement of DMA in human plasma. After precipitation of plasma proteins with acetonitrile followed by dilution (1:4) with water, the extract was injected onto the HPLC and detected at 195 nm. Separation was performed using a Cogent-HPS 5 μm C18 column (250 × 4.6 mm) preceded by a Brownlee 7 μm RP18 , pre-column (1.5 cm × 3.2 mm). The mobile phase was 25 mm sodium phosphate buffer (pH 3), containing 2.5% (v/v) acetonitrile and 0.0005% (v/v) sodium-octyl-sulfonate. Using a flow rate of 1 mL/min, the retention times of DMA and the internal standard (IS), 2-chloroacetamide, were 9.5 and 3.5 min, respectively. Peak area ratio (DMA:IS) was a linear function of concentration from 1 to 1000 μg/mL. There was excellent intraday precision (<5% for 5-700 μg/mL DMA), accuracy (<3% deviation from the true concentration) and recovery (74-98%). The limits of detection and quantification were 1 and 5 μg/mL, respectively. In eight children who received intravenous busulfan, DMA concentrations ranged from 110 to 438 μg/mL.

  2. Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

    PubMed

    Roswell, Robert O; Greet, Brian; Shah, Sunny; Bernard, Samuel; Milin, Alexandra; Lobach, Iryna; Guo, Yu; Radford, Martha J; Berger, Jeffrey S

    2016-08-01

    Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.

  3. Intravenous cannulation of hens for long-term infusion.

    PubMed

    Hamilton, R M

    1978-12-01

    Intravenous cannulation was performed on the brachial vein of the hen. The cannulation system consisted of a jacket that fitted around the body of the hen. An external sheath passed through the top of the cage, over a small pulley and was counter-weighted with lead. A subcutaneous polyethylene sheath was extended from the wing near the site of cannulation to the mid-point of the back between the wings and into the external sheath. Once the polyethylene cannula was inserted into and attached to the brachial vein, the free end was passed through the subcutaneous sheath, into and through the external sheath, and attached to a syringe or pump. No special post-cannulation care was necessary. The hens were housed in wire cages and received feed and water ad libitum. Twenty-four hens were continuously or intermittently infused for up to 73 days after cannulation.

  4. Comparison of intravenous acetylsalicylic acid and dipyrone in postoperative pain

    PubMed Central

    Blendinger, I.; Eberlein, H. J.

    1980-01-01

    1 In 17 gynaecological patients with postoperative pain the analgesic efficacy of intravenous lysine salicylate 1.8 g (corresponding to acetylsalicyclic acid (ASA) 1.0 g) and dipyrone 1.0 g were compared in a double-blind randomized study. 2 In the ASA group, mean pain relief and pain intensity difference scores reached a maximum 30 min after drug administration and remained at this level for the next 90 minutes. 3 In the dipyrone group, these scores reached their peak 60 min after drug administration and seemed to fall off during the next hour. 4 The mean pain relief and intensity difference scores were greater following aspirin than dipyrone. However, firm conclusions cannot be drawn from the results of this small study. PMID:7437274

  5. Fat emulsion for intravenous administration: clinical experience with intralipid 10%.

    PubMed Central

    Hansen, L M; Hardie, B S; Hidalgo, J

    1976-01-01

    A 10% soybean oil emulsion (Intralipid 10%), used extensively in Europe for intravenous alimentation, has now been clinically evaluated in the United States. Controlled studies have shown that the soybean oil emulsion can be substituted for glucose to supply one-third to two-thirds of the total calories, and can be administered peripherally without significant vein irritation. Essential fatty acid deficiencies, frequently encountered in patients dependent on parenteral alimentation with fat-free solutions, are prevented and corrected by use of this preparation. Data on long-term tolerance to Intralipid 10% infusions are presented for 292 patients treated for more than 6,000 patient days. The soybean oil emulsion was usually well tolerated. Side effects were reported in two of 133 adults and 12 of 159 pediatric patients. PMID:820291

  6. The Utilization of Long Nylon Catheters for Prolonged Intravenous Infusions

    PubMed Central

    Roy, Ronald B.; Wilkinson, R. H.; Bayliss, C. E.

    1967-01-01

    A study of 300 patients receiving intravenous therapy showed that 90 had associated phlebitis. Because of this high rate of complications, the use of long plastic catheters, with the tip located in a large central vessel, was investigated. One hundred and one catheters were inserted into the basilic vein through a cut-down. The patients were divided into four groups: infusions lasting one to seven days, eight to 14 days, 15 to 28 days and 29 days or longer. The most common complication was obstruction of the catheter with clotted blood. In four patients the catheters had to be removed because of phlebitis; two were pulled out by the patients themselves. Infection was not observed. Two factors probably contributed to the successful infusions: the composition of the plastic catheters (nylon) and the location of the tip in a large central vessel. ImagesFig. 1Fig. 2Fig. 3 PMID:6017172

  7. Quality of intravenous infusion fluids manufactured in Kenya.

    PubMed

    Aluoch-Orwa, J A; Ondari, C O; Kibwage, I O; Hoogmartens, J

    1995-12-01

    The incidence and nature of microbial contamination of intravenous fluids prepared by four manufacturing establishments in Kenya was evaluated using the European Pharmacopoeia membrane filtration method for sterility testing. The percentage failures were 28.6% for source D, 18.8% for source A, 12.5% for source B and 10.5% for source C. The major contaminant was aspergillus which was isolated from samples from three sources. Candida and Staphylococcus accounted for the contamination of samples from two sources. Failure rates due to the chemical composition of the products was 66.7% for Source A, 60.0% for D, 41.7% for C and 13.3% for B. The experience of the manufacturing sites appeared to correlate with the quality of the products, with the older manufacturing establishments showing lower percentage failures.

  8. Clinical perspectives of intravenous ketamine anaesthesia in peafowl (Pavo cristatus).

    PubMed

    Athar, M; Shakoor, A; Muhammad, G; Sarwar, M N; Chaudhry, N I

    1996-01-01

    A total of 29 peafowl (Pavo cristatus), rectified surgically for infraorbital abscesses (n = 22), lacerated wounds (n = 4), and fractures of tibia (n = 2) and radius (n = 1), were anaesthetized by the intravenous administration of ketamine hydrochloride (Inj. Calypsol, Gedeon Richter, Hungary) in a dose of 15 20 mg/kg body weight. Divided doses (10 mg + 5 mg + 5 mg) were used with an interval of 1-2 min. No premedication was undertaken in any of the birds. Anaesthesia lasted for about 15 min and the birds gained their feet completely after 30 min to 3 hours. The respiration rate was markedly depressed (8-10/min) and the respiratory pattern was deep abdominal. Only a slight increase was observed in the heart rate. Analgesia was incomplete and muscle relaxation was not satisfactory. Mild salivation was also noticed in some of the birds (n = 3). Recovery, although not smooth, was uneventful.

  9. Modelling Framework and Assistive Device for Peripheral Intravenous Injections

    NASA Astrophysics Data System (ADS)

    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.

  10. Assessment of the pharmacodynamics of intranasal, intravenous and oral scopolamine

    NASA Technical Reports Server (NTRS)

    Tietze, Karen J.

    1990-01-01

    Space motion sickness is an important issue in the space medical sciences program. One of the objectives of the ongoing clinical experimental protocol Pharmacokinetics of Intranasal Scopolamine in Normal Subjects is to evaluate the pharmacodynamics of scopolamine using salivary flow rate and pH profiles and cognitive performance tests as pharmacodynamic parameters. Normal volunteers collected saliva and performed the NTI Multiresource Performance Battery tests at designed time intervals to establish control saliva flow rates, salivary pH profiles, and the characteristics of the learning curve for the performance program under normal conditions. In the clinical part of the study, saliva samples and performance test scores are collected from healthy nonsmoking subjects after receiving a single 0.4 mg dose of either intranasal, intravenous, or oral scopolamine.

  11. Sonographically guided placement of intravenous catheters in minipigs.

    PubMed

    Pinkernelle, Jens; Raschzok, Nathanael; Teichgräber, Ulf K M

    2009-07-01

    Many procedures in minipigs require establishment of reliable deep venous access with a large-bore catheter. In animal experiments, such catheters are typically implanted surgically. In clinical settings, however, ultrasound imaging is routinely used to facilitate safe, minimally invasive puncture of deep vessels. The authors describe a technique for using ultrasound guidance to puncture and cannulate the minipig femoral vein. They carried out the procedure in six minipigs for the purpose of injecting contrast agents for subsequent imaging scans. The procedure was ultimately successful in all pigs, took 10 min on average and resulted in no physiological complications. In one minipig, however, a 10-cm-long catheter became dislodged from the femoral vein; use of a longer (25-cm-long) catheter was optimal for establishing reliable intravenous access.

  12. Biodistribution of quantum dots in the kidney after intravenous injection.

    PubMed

    Pollinger, K; Hennig, R; Bauer, S; Breunig, M; Tessmar, J; Buschauer, A; Witzgall, R; Goepferich, A

    2014-05-01

    The biodistribution of nanoparticles is a major subject of current nanomedical research. To date, however, the exact investigation of nanoparticle fate in the microenvironment of a main excretory organ, the kidney has largely been neglected. In this study, the biodistribution of polyethylene glycol-coated quantum dots (Qdots) with special focus on their interaction with the kidney is investigated. Upon intravenous injection, nanoparticles showed effective blood circulation in mice and significant renal accumulation after two hours. Histological analysis of the kidney revealed that Qdots were strongly associated to the intraglomerular mesangial cells. This preferential deposition of nanoparticles in the kidney mesangium is highly promising, since it could be of utmost value for site-specific treatment of severe kidney diseases like diabetic nephropathy in the future.

  13. [Hypokalemic effect of salbutamol administered intravenously in the preoperative period].

    PubMed

    Fábregas, N; Taurá, P; Castillo, J; Tomás, A; Planella, V L; Naldá, M A

    1989-01-01

    In 8 healthy patients (ASA I-II) there was analyzed the effect of salbutamol over serum levels of potassium, glucose, insulin, AMPc and GMPc. Also were determined the arterial blood pressure and heart rate. The drug was administered intravenously, as bronchodilator, during the preoperative period. There was a significant decrease in kaliemia (p less than 0.001 immediately after receiving the salbutamol infusion and p less than 0.05 at 60 min). Their plasma potassium levels dropped from 4.03 +/- 25 to 3.45 +/- 0.16 mEq.l-1. The plasma levels of glucose and insulin increased with a significance of p less than 0.001 post salbutamol perfusion. There were no changes in the plasmatic AMPc and GMPc. Heart rate increased from 67 +/- 10.8 to 80.5 +/- 13.7 (p less than 0.01) post perfusion, returning afterwards to their basal values. Arterial blood pressure was unmodified.

  14. The use of intravenous cannulae and the occurrence of thrombophlebitis.

    PubMed

    van den Broek, P J; de Herder-Swinkels, J M; Moffie, B G; van den Berg, W H; Hermans, J

    1989-01-01

    The occurrence of thrombophlebitis in a coronary care unit was studied in relation to the use of short plastic intravenous cannulae. The incidence of thrombophlebitis was 51% in cases where cannulae were used for continuous infusion of glucose 5% and 13% for cannulae which were locked after the injection of heparin. Only one case of infectious thrombophlebitis was seen. The other cases of thrombophlebitis had a chemical or mechanical aetiology. Replacement of glucose 5% by a NaCl 0.9% solution for continuous infusion reduced the incidence of thrombophlebitis to 33%. Heparin-locked cannulae, to provide rapid access to the patient's circulation, proved to be a safe alternative to continuous infusion.

  15. Intravenous immunoglobulin in neurological disease: a specialist review

    PubMed Central

    Wiles, C; Brown, P; Chapel, H; Guerrini, R; Hughes, R; Martin, T; McCrone, P; Newsom-Davis, J; Palace, J; Rees, J; Rose, M; Scolding, N; Webster, A

    2002-01-01

    Treatment of neurological disorders with intravenous immunoglobulin (IVIg) is an increasing feature of our practice for an expanding range of indications. For some there is evidence of benefit from randomised controlled trials, whereas for others evidence is anecdotal. The relative rarity of some of the disorders means that good randomised control trials will be difficult to deliver. Meanwhile, the treatment is costly and pressure to "do something" in often distressing disorders considerable. This review follows a 1 day meeting of the authors in November 2000 and examines current evidence for the use of IVIg in neurological conditions and comments on mechanisms of action, delivery, safety and tolerability, and health economic issues. Evidence of efficacy has been classified into levels for healthcare interventions (tables 1 and 2). PMID:11909900

  16. [Readaptation after total intravenous anesthesia in one-day surgery].

    PubMed

    Buravtsev, V A; Medvinskiĭ, I D

    1997-01-01

    The authors analyze the stages of readaptation and recovery of clear consciousness in the immediate postoperative period in 200 patients administered one of the four variants of intravenous anesthesia in a one-day surgical hospital. The purpose of this work was to optimize the anesthetic care and the readaptation period. The stages of readaptation were assessed by psychophysiological testing. This process coursed most smoothly after propofol-phentanyl and hypnomidate-phentanyl anesthesia. Readaptation after sombrevin-phentanyl coursed reliably slower. The longest recovery was observed after calipsol-diazepam anesthesia, despite drug stimulation. This type of narcosis is irrational for one-day surgery, for it requires prolonged postoperative monitoring and thus makes the hospital stay longer.

  17. Intravenous nitroglycerin for rest angina. Potential pathophysiologic mechanisms of action.

    PubMed

    DePace, N L; Herling, I M; Kotler, M N; Hakki, A H; Spielman, S R; Segal, B L

    1982-10-01

    Twenty patients with refractory rest angina pectoris were treated with intravenously (IV) administered nitroglycerin (mean dosage, 72.4 micrograms/min; range, 15 to 226 micrograms/min). There was a considerable reduction or abolition in the number of ischemic episodes in 85% of patients without overall substantial changes in heart rate, mean arterial BP, pulmonary capillary wedge pressure (PCWP), and pulmonary arterial mean pressure. However, those patients with an initial PCWP of more than 12 mm Hg or a systolic pressure of more than 130 mm Hg had a substantial reduction in PCWP and systolic BP following IV nitroglycerin. We conclude that IV nitroglycerin may relieve rest angina by different pathophysiologic mechanisms. In some patients, IV nitroglycerin favorably altered the hemodynamic determinants of myocardial oxygen consumption. In others, however, no change in these determinants occurred, suggesting a direct effect on the coronary circulation.

  18. Quinine-induced thrombocytopenia following intravenous use of heroin

    SciTech Connect

    Christie, D.J.; Walker, R.H.; Kolins, M.D.; Wilner, F.M.; Aster, R.H.

    1983-06-01

    Profound thrombocytopenia developed in a 22-year-old man after intravenous use of heroin. A high-titer, quinine-dependent, platelet-specific antibody was detected in his serum using lysis of normal platelets labeled with chromium 51 and an electroimmunoassay for measurement of platelet-associated IgG. The antibody was specific for quinine and failed to react with platelets in the presence of quinidine hydrochloride or two structural analogues of heroin. Quinine, a common adulterant found in heroin, was detected in the patient's blood and urine. On the basis of these observations, the patient was judged to have quinine-induced immunologic thrombocytopenia. To our knowledge, this report is the first to confirm that quinine used as an adulterant can induce immunologic thrombocytopenia following an injection of heroin.

  19. Pulmonary 'mainline' granulomatosis: talcosis of intravenous methadone abuse.

    PubMed

    Paré, J A; Fraser, R G; Hogg, J C; Howlett, J G; Murphy, S B

    1979-05-01

    Seventeen intravenous abusers of methadone underwent clinical, roentgenologic and physiologic assessment. Two complained of dyspnea on exertion and two had cor pulmonale. Of 15 patients whose fundi were examined, nine had talc particles in their retinal vessels. The chest roentgenograms of seven showed a diffuse pin-point micronodular pattern and two of the seven also manifested volume loss, one with coalescence of opacities simulating progressive massive fibrosis. Twelve patients had some degree of pulmonary dysfunction, 10 with lowered steady state diffusing capacity and 11 with decreased flow rates (FEV1 and MMF). There was no hyperinflation, but two showed an increase in residual volume. Corticosteroid therapy was attempted on two and was ineffective. Necropsy on the one patient who died revealed severe pulmonary fibrosis and talc granulomas in lungs, liver, kidneys and lymph nodes.

  20. Intravenous tacrolimus and cyclosporine induced anaphylaxis: what is next?

    PubMed

    Kang, Sung-Yoon; Sohn, Kyoung-Hee; Lee, Jeong-Ok; Kim, Sae-Hoon; Cho, Sang-Heon; Chang, Yoon-Seok

    2015-07-01

    Tacrolimus and cyclosporine have been used in various formulations, but their hypersensitivity reactions are rare in practice. Castor oil derivatives are nonionic surfactants used in aqueous preparations of hydrophobic active pharmaceutical ingredients. Castor oil derivatives that can be used as additives to tacrolimus and cyclosporine may play a role in the development of hypersensitivity reactions, especially anaphylaxis. Various immunologic and nonimmunologic mechanisms have been implicated in hypersensitivity reactions induced by castor oil derivatives. Physicians should be aware that not only the drug itself, but also its additives or metabolites could induce hypersensitivity reactions. We report a case of anaphylaxis caused by vitamin K (phytonadine), serotonin antagonist (granisetron), intravenous tacrolimus, and cyclosporine. Interestingly, the patient tolerated oral cyclosporine, which did not contain Cremophor EL or polysorbate 80.

  1. Cangrelor: a novel intravenous antiplatelet agent with a questionable future.

    PubMed

    Waite, Laura H; Phan, Yvonne L; Spinler, Sarah A

    2014-10-01

    Current percutaneous coronary intervention (PCI) guidelines recommend the use of a P2Y12 inhibitor with aspirin and an injectable anticoagulant. However, available oral P2Y12 inhibitor therapy is limited by significant drug interactions, unclear oral absorption in selected clinical conditions, and delayed onset and offset of activity that may be cumbersome for patients requiring coronary artery bypass graft (CABG) surgery. Cangrelor, a novel intravenous P2Y12 inhibitor, offers potential advantages compared with currently available oral agents, particularly in regard to rapid onset and offset of platelet inhibition. The Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) trials compared cangrelor versus an oral loading dose of clopidogrel, given before or after PCI, in patients with both stable and acute coronary syndromes. The results were conflicting, but some evidence demonstrated a lower rate of stent thrombosis compared with clopidogrel and lower rates of a composite cardiovascular end point, with comparable bleeding rates. The BRIDGE study assessed cangrelor as a replacement for oral P2Y12 inhibitors in patients awaiting CABG surgery and demonstrated that cangrelor maintained platelet inhibition during the preoperative period and enabled a rapid return to baseline platelet function upon cessation of the infusion. A new drug application was submitted to the Food and Drug Administration (FDA) for use during PCI to prevent thrombotic events and as bridging therapy for patients awaiting surgery who require therapy with P2Y12 inhibitors. In February 2014, the FDA's Cardiovascular and Renal Drugs Advisory Committee recommended against approval due to concerns over an appropriate risk-benefit ratio for use during PCI and a lack of evidence supporting the bridging indication. On April 30, 2014, the FDA issued a Complete Response letter for the PCI and bridging indications, denying approval and requesting further data. The

  2. Intravenous iron in a primary-care clinic.

    PubMed

    Maslovsky, I

    2005-04-01

    The preferable route of iron delivery for most iron-deficient patients is oral. Parenteral iron therapy is used in patients who cannot tolerate oral iron or in cases in which oral iron is not sufficiently effective. The most frequent indications for parenteral iron therapy are unbearable gastrointestinal side effects induced by oral iron itself, worsening of inflammatory bowel disease symptoms, insufficient intestinal absorption, renal failure-caused anemia that is treated with erythropoietin, and unresolved ongoing bleeding, which would cause the acceptable oral doses of iron therapy to be exceeded. The serious adverse effects of iron dextran that was used in the past could explain the reluctance of medical personnel to prescribe this effective treatment. Patients with iron deficiency anemia were treated with intravenous iron in a primary care clinic. The iron gluconate was given in a dosage of 62.5 mg diluted in 150 mL of normal saline and was infused intravenously over 30 min, while iron sucrose was given in a dosage of 100 mg diluted in the same volume of normal saline and given at the same rate. In total, 724 infusions were administered to 57 patients. Iron sucrose was used in 628 infusions, and iron gluconate was used in the remaining 96. The frequency of the infusion treatments depended on the underlying disease and ranged from three times a week to once a month. Adverse effects were seldom observed and were minor in patients receiving iron gluconate, and were not registered at all in patients treated with iron sucrose. Two cases of flushing with paresthesias occurred. Slowing the infusion rate successfully eliminated these side effects. One case of hypotension was treated successfully with 500 cc of normal saline infusion. One case of dropout occurred, due to the patient's refusal to cooperate. No anaphylactic reactions were observed. Iron gluconate and iron sucrose are effective and safe for use in primary care clinics. The risk of adverse effects is low.

  3. Potential intravenous drug incompatibilities in a pediatric unit

    PubMed Central

    Leal, Karla Dalliane Batista; Leopoldino, Ramon Weyler Duarte; Martins, Rand Randall; Veríssimo, Lourena Mafra

    2016-01-01

    ABSTRACT Objective To investigate potential intravenous drug incompatibilities and related risk factors in a pediatric unit. Methods A cross-sectional analytical study conducted in the pediatric unit of a university hospital in Brazil. Data on prescriptions given to children aged 0-15 years from June to October 2014 were collected. Prescriptions that did not include intravenous drugs and prescriptions with incomplete dosage regimen or written in poor handwriting were excluded. Associations between variables and the risk of potential incompatibility were investigated using the Student’s t test and ANOVA; the level of significance was set at 5% (p<0.05). Relative risks were calculated for each drug involved in potential incompatibility with 95% confidence interval. Results A total of 222 children participated in the study; 132 (59.5%) children were male and 118 (53.2%) were aged between 0 and 2 years. The mean length of stay was 7.7±2.3 days. Dipyrone, penicillin G and ceftriaxona were the most commonly prescribed drugs. At least one potential incompatibility was detected in about 85% of children (1.2 incompatibility/patient ratio). Most incompatibilities detected fell into the non-tested (93.4%), precipitation (5.5%), turbidity (0.7%) or chemical decomposition (0.4%) categories. The number of drugs and prescription of diazepam, phenytoin, phenobarbital or metronidazole were risk factors for potential incompatibility. Conclusion Most pediatric prescriptions involved potential incompatibilities, with higher prevalence of non-tested incompatibilities. The number of drugs and prescription of diazepam, phenobarbital, phenytoin or metronidazole were risk factors for potential incompatibilities. PMID:27462891

  4. Intravenous pamidronate treatment of infants with severe osteogenesis imperfecta

    PubMed Central

    Åström, Eva; Jorulf, Håkan; Söderhäll, Stefan

    2007-01-01

    Objective Children with the severe forms of osteogenesis imperfecta have in several studies been treated with intravenous pamidronate, but there are only few reports of the effect of early treatment. Aim To evaluate the effect of treatment started in infancy. Methods In a prospective observational study, with a historic control group, intravenous disodium pamidronate (APD) was given as monthly infusions to 11 children with osteogenesis imperfecta aged 3–13 (median 3.6) months, who had severe osteogenesis imperfecta with congenital bowing of the femora and vertebral compression fractures. Results During treatment of children aged between 3 and 6 (median 4.5) years, dual‐energy x ray absorptiometry measurements of the lumbar spine showed a gradual increase in bone density. Bone metabolism parameters in serum (alkaline phosphatase, osteocalcin, procollagen 1 carboxy‐terminal peptide, collagen 1 teleopeptide) and in urine (deoxypyridinoline) indicated a decrease in bone turnover. An improvement of mobility was seen and at the latest recording, at the age of 3.3–6.5 (median 4.8) years, the children could all walk. Vertebral remodelling was seen, with increased vertebral height, and no child developed scoliosis, kyphosis or basilar impression. All children required femoral intramedullar rods for fractures, and five needed tibial rodding for extreme curvatures that prevented functional standing and walking. No adverse effects were seen on growth, fracture healing or blood chemistry. Conclusions APD is an efficient symptomatic treatment for infants with severe osteogenesis imperfecta, but additional orthopaedic surgery is often needed. Early treatment may prevent scoliosis and basilar impression. Long‐term follow‐up is important. PMID:17114205

  5. Intravenous Thrombolysis for Acute Ischemic Stroke: Review of 97 Patients

    PubMed Central

    Mehta, Anish; Mahale, Rohan; Buddaraju, Kiran; Majeed, Anas; Sharma, Suryanarayana; Javali, Mahendra; Acharya, Purushottam; Srinivasa, Rangasetty

    2017-01-01

    Background: Intravenous thrombolysis (IVT) has now become a standard treatment in eligible patients with acute ischemic stroke (AIS) who present within 4.5 h of symptom onset. Objective: To determine the usefulness of IVT and the subset of patients who will benefit from IVT in AIS within 4.5 h. Materials and Methods: Patients with AIS within 4.5 h of symptom onset who underwent IVT were studied prospectively. The study period was from October 2011 to October 2015. Results: A total of 97 patients were thrombolysed intravenously. The mean onset to needle time in all patients was 177.2 ± 62 min (range: 60–360). At 3 months follow-up, favorable outcome was seen in 65 patients (67.1%) and poor outcome including death in the remaining 32 patients (32.9%). Factors predicting favorable outcome was age <65 years (P = 0.02), the National Institute of Health Stroke Scale (NIHSS) <15 (P < 0.001), small vessel occlusion (P = 0.006), cardioembolism (P = 0.006), and random blood sugar (RBS) <250 mg/dl (P < 0.001). Factors predicting poor outcome was diabetes mellitus (P = 0.01), dyslipidemia (P = 0.01), NIHSS at admission >15 (P = 0.03), RBS >250 mg/dl (P = 0.01), Dense cerebral artery sign, age, glucose level on admission, onset-to-treatment time, NIHSS on admission score >5 (P = 0.03), and occlusion of large artery (P = 0.02). Conclusion: Milder baseline stroke severity, blood glucose <250 mg/dL, younger patients (<65 years), cardioembolic stroke, and small vessel occlusion benefit from recombinant tissue plasminogen activator. PMID:28149079

  6. Intravenous magnesium in experimental stent thrombosis in swine.

    PubMed

    Rukshin, V; Azarbal, B; Shah, P K; Tsang, V T; Shechter, M; Finkelstein, A; Cercek, B; Kaul, S

    2001-09-01

    We investigated the effects of magnesium on acute platelet-dependent stent thrombosis in an ex vivo porcine arteriovenous shunt model of high-shear blood flow. Control nitinol stents were expanded to 2 mm in diameter in a tubular perfusion chamber interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100 s(-1) for 20 minutes (n=156 perfusion runs in 10 swine). Animals were treated with intravenous heparin or MgSO(4) alone (2 g bolus over 20 minutes, followed by 2 g/h infusion) and combined heparin plus MgSO(4) in random fashion. Effects on thrombus weight (TW), platelet aggregation, bleeding time, activated clotting time, mean arterial blood pressure, and heart rate were quantified. Data points in the magnesium-treated animals were examined within 20 minutes after bolus (Mg-early) and >40 minutes after bolus (Mg-late). Stent TW (20+/-3 mg, pretreatment) was reduced by 42+/-21%, 47+/-19%, 48+/-16%, 67+/-12%, and 86+/-8% in the groups treated with Mg-early alone, Mg-late alone, heparin alone, heparin+Mg-early, and heparin+Mg-late, respectively (all P<0.001 versus pretreatment, P<0.001 for heparin+Mg-early and Mg-late versus heparin or magnesium alone, and P<0.05 for heparin+Mg-late versus heparin+Mg-early, ANOVA). Magnesium had no significant effect on platelet aggregation, activated clotting time, or bleeding time. There were no significant effects on heart rate or mean arterial blood pressure. The serum magnesium level was inversely correlated with TW (r=-0.70, P=0.002). In conclusion, treatment with intravenous MgSO(4) produced a time-dependent inhibition of acute stent thrombosis under high-shear flow conditions without any hemostatic or significant hemodynamic complications. Thus, magnesium may be an effective agent for preventing stent thrombosis.

  7. Large osteoclasts in pediatric osteogenesis imperfecta patients receiving intravenous pamidronate.

    PubMed

    Cheung, Moira S; Glorieux, Francis H; Rauch, Frank

    2009-04-01

    Intravenous pamidronate is widely used to treat children with moderate to severe osteogenesis imperfecta (OI). Changes in the appearance of osteoclasts have previously been noted in children receiving pamidronate and have been interpreted as signs of toxicity. In this study, we analyzed osteoclast parameters in paired iliac bone specimens before and after 2-4 yr of cyclical intravenous pamidronate therapy in 44 pediatric OI patients (age range: 1.4-17.5 yr; 21 girls). During pamidronate treatment, average osteoclast diameter and the mean number of nuclei present per osteoclast increased by 18% (p = 0.02) and 43% (p < 0.001), respectively. The number of samples containing large osteoclasts (LOcs, diameter > 50 mum) increased from 6 (14%) before treatment to 23 (52%) after pamidronate therapy (p < 0.001 by chi(2) test). Post-treatment samples containing LOcs had a greater core width (p = 0.04) and a higher cancellous bone volume per tissue volume (p < 0.001), because cancellous bone volume had increased more during pamidronate treatment (p < 0.001). Osteoclast number and surface were higher in samples with LOcs, but there was no difference in cancellous bone formation parameters. The presence of LOcs was independent of OI type, type of collagen type I mutation, lumbar spine BMD, and other clinical or biochemical measures. In conclusion, this study did not show any indication that LOcs during pamidronate treatment are indicative of toxicity. It seems more likely that the observed abnormalities in osteoclast morphology are part of the mechanism of action of this drug.

  8. Developmental toxicity of intravenously injected zinc oxide nanoparticles in rats.

    PubMed

    Lee, Jinsoo; Yu, Wook-Joon; Song, Jeongah; Sung, Changhyun; Jeong, Eun Ju; Han, Ji-Seok; Kim, Pilje; Jo, Eunhye; Eom, Ikchun; Kim, Hyun-Mi; Kwon, Jung-Taek; Choi, Kyunghee; Choi, Jonghye; Kim, Heyjin; Lee, Handule; Park, Juyoung; Jin, Seon Mi; Park, Kwangsik

    2016-12-01

    Recent toxicity studies of zinc oxide nanoparticles by oral administration showed relatively low toxicity, which may be resulted from low bioavailability. So, the intrinsic toxicity of zinc oxide nanoparticles needs to be evaluated in the target organs by intravenous injection for full systemic concentration of the administered dosage. Although the exposure chance of injection route is low compared to oral and/or inhalation route, it is important to see the toxicity with different exposure routes to get better risk management tool. In this study, the effects of zinc oxide nanoparticles on dams and fetuses were investigated in rats after intravenous injection (5, 10, and 20 mg/kg) from gestation day 6 to 20. Two of 20 dams in the 20 mg/kg treatment group died during the treatment period. Hematological examination and serum biochemistry showed dose-dependent toxicity in treated dams. Histopathological analysis of treated dams revealed multifocal mixed cell infiltration and thrombosis in lung, tubular dilation in kidneys, and extramedullary hemopoiesis in liver. Total dead fetuses (post-implantation loss) were increased and the body weight of fetus was decreased in the 20 mg/kg treatment group. Statistical differences in corpora lutea, resorption, placental weight, morphological alterations including external, visceral and skeletal malformations were not observed in treated groups. Based on the data, lowest observed adverse effect level of injection route was suggested to be 5 mg/kg in dams and no observed adverse effect level was suggested to be 10 mg/kg in fetal developmental toxicity.

  9. Final Report for Intravenous Fluid Generation (IVGEN) Spaceflight Experiment

    NASA Technical Reports Server (NTRS)

    McQuillen, John B.; McKay, Terri L.; Griffin, DeVon W.; Brown, Dan F.; Zoldak, John T.

    2011-01-01

    NASA designed and operated the Intravenous Fluid Generation (IVGEN) experiment onboard the International Space Station (ISS), Increment 23/24, during May 2010. This hardware was a demonstration experiment to generate intravenous (IV) fluid from ISS Water Processing Assembly (WPA) potable water using a water purification technique and pharmaceutical mixing system. The IVGEN experiment utilizes a deionizing resin bed to remove contaminants from feedstock water to a purity level that meets the standards of the United States Pharmacopeia (USP), the governing body for pharmaceuticals in the United States. The water was then introduced into an IV bag where the fluid was mixed with USP-grade crystalline salt to produce USP normal saline (NS). Inline conductivity sensors quantified the feedstock water quality, output water purity, and NS mixing uniformity. Six 1.5-L bags of purified water were produced. Two of these bags were mixed with sodium chloride to make 0.9 percent NS solution. These two bags were returned to Earth to test for compliance with USP requirements. On-orbit results indicated that all of the experimental success criteria were met with the exception of the salt concentration. Problems with a large air bubble in the first bag of purified water resulted in a slightly concentrated saline solution of 117 percent of the target value of 0.9 g/L. The second bag had an inadequate amount of salt premeasured into the mixing bag resulting in a slightly deficient salt concentration of 93.8 percent of the target value. The USP permits a range from 95 to 105 percent of the target value. The testing plans for improvements for an operational system are also presented.

  10. Analgesic effects of palonosetron in the intravenous propofol injection

    PubMed Central

    Ryu, Han-Bom

    2014-01-01

    Background Propofol is a good induction agent, but it has the disadvantage of causing pain on intravenous injection. The incidence of propofol-induced pain is approximately 70%. Palonosetron is a novel second-generation 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist. We presumed that palonosetron would be effective in reducing the occurrence of propofol-induced pain based on similar mechanisms to other 5-HT3 receptor antagonists. Methods Eighty patients were randomized to either Group N (0.9% sodium chloride [normal saline] 2 ml, n = 40) or Group P (palonosetron 0.075 mg, 2 ml, n = 40). Patients were intravenously given a 2 ml pretreatment solution, containing either palonosetron 0.075 mg or normal saline. Following pretreatment with 2 ml of palonosetron 0.075 mg or normal saline, we manually occluded venous drainage midarm with the help of an assistant. One minute later, we released the occlusion of venous drainage. This was followed by a 5-second propofol injection at 25% of the total calculated doses. Patients were then interviewed about whether or not they experienced propofol-induced pain. Results Overall, the incidence of propofol-induced pain was 60% in the normal saline group and 27.5% in the palonosetron group. No patients in the palonosetron group experienced severe pain. The incidence of propofol-induced pain was significantly lower in the palonosetron group compared to the normal saline group (P < 0.01). Conclusions Following pretreatment with palonosetron, 72.5% of patients experienced a decrease in the occurrence of propofol-induced pain. PMID:24624266

  11. Evaluation of intravenous hydroxylethyl starch, intravenous albumin 20%, and oral cabergoline for prevention of ovarian hyperstimulation syndrome in patients undergoing ovulation induction

    PubMed Central

    Ghahiri, Ataollah; Mogharehabed, Neda; Movahedi, Minoo; Hosseini, Naeimehossadat

    2015-01-01

    Background: The purpose of this study was to compare the three different strategies, intravenous (IV) hydroxylethyl starch (HES), IV human albumin (HA), and oral Cabergoline (Cb) in the prevention of ovarian hyperstimulation syndrome (OHSS). Materials and Methods: In this prospective randomized clinical trial, 91 women at high risk of developing OHSS were allocated into the three groups, group one received 2 vial (2 × 50 ml) IV HAs, in group two, 1000 ml of 6% HES was administered IV, both groups 30 min after oocyte retrieval within 4 h. Group three, 31 infertile patients received oral Cb 0.5 mg daily for 7 days after oocyte retrieval. Patients were visited 14 ± 1 days after in-vitro fertilization and if β-human chorionic gonadotropin level >10, transvaginal ultrasonography was performed 2 weeks later to confirm intrauterine pregnancy. Patients were followed up weekly for 3 months for signs of OHSS and were also informed about the signs of OHSS and asked to contact immediately if any symptoms of were detected. Results: None of the participants in group HES developed severe OHSS and only 3 patients (10%) developed mild to moderate OHSS. The incident of severe OHSS was significantly higher in albumin group compared to Cb and HES group (P = 0.033 and P < 0.001, respectively). Also, the probability of developing severe OHSS was higher in Cb group than group HES (P = 0.031). Conclusion: The findings from this study suggest that administration of 1000 ml of HES 6% has a higher prophylactic effect compared to administration of IV HA and oral Cb. PMID:26622260

  12. Predicting the Response to Intravenous Immunoglobulins in an Animal Model of Chronic Neuritis

    PubMed Central

    Pfaff, Johannes; Mathys, Christian; Mausberg, Anne K.; Bendszus, Martin; Pham, Mirko; Hartung, Hans-Peter; Kieseier, Bernd C.

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disabling autoimmune disorder of the peripheral nervous system (PNS). Intravenous immunoglobulins (IVIg) are effective in CIDP, but the treatment response varies greatly between individual patients. Understanding this interindividual variability and predicting the response to IVIg constitute major clinical challenges in CIDP. We previously established intercellular adhesion molecule (ICAM)-1 deficient non-obese diabetic (NOD) mice as a novel animal model of CIDP. Here, we demonstrate that similar to human CIDP patients, ICAM-1 deficient NOD mice respond to IVIg treatment by clinical and histological measures. Nerve magnetic resonance imaging and histology demonstrated that IVIg ameliorates abnormalities preferentially in distal parts of the sciatic nerve branches. The IVIg treatment response also featured great heterogeneity allowing us to identify IVIg responders and non-responders. An increased production of interleukin (IL)-17 positively predicted IVIg treatment responses. In human sural nerve biopsy sections, high numbers of IL-17 producing cells were associated with younger age and shorter disease duration. Thus, our novel animal model can be utilized to identify prognostic markers of treatment responses in chronic inflammatory neuropathies and we identify IL-17 production as one potential such prognostic marker. PMID:27711247

  13. Intravenous mesenchymal stem cells prevented rejection of allogeneic corneal transplants by aborting the early inflammatory response.

    PubMed

    Oh, Joo Youn; Lee, Ryang Hwa; Yu, Ji Min; Ko, Jung Hwa; Lee, Hyun Ju; Ko, Ah Young; Roddy, Gavin W; Prockop, Darwin J

    2012-11-01

    Mesenchymal stem/progenitor cells (MSCs) were reported to enhance the survival of cellular and organ transplants. However, their mode of action was not established. We here used a mouse model of corneal allotransplantation and demonstrated that peri-transplant intravenous (i.v.) infusion of human MSCs (hMSCs) decreased the early surgically induced inflammation and reduced the activation of antigen-presenting cells (APCs) in the cornea and draining lymph nodes (DLNs). Subsequently, immune rejection was decreased, and allograft survival was prolonged. Quantitative assays for human GAPDH revealed that <10 hMSCs out of 1 × 10(6) injected cells were recovered in the cornea 10 hours to 28 days after i.v. infusion. Most of hMSCs were trapped in lungs where they were activated to increase expression of the gene for a multifunctional anti-inflammatory protein tumor necrosis factor-α stimulated gene/protein 6 (TSG-6). i.v. hMSCs with a knockdown of TSG-6 did not suppress the early inflammation and failed to prolong the allograft survival. Also, i.v. infusion of recombinant TSG-6 reproduced the effects of hMSCs. Results suggest that hMSCs improve the survival of corneal allografts without engraftment and primarily by secreting TSG-6 that acts by aborting early inflammatory responses. The same mechanism may explain previous reports that MSCs decrease rejection of other organ transplants.

  14. Intravenous immunoglobulin-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients

    PubMed Central

    Sharma, Meenu; Schoindre, Yoland; Hegde, Pushpa; Saha, Chaitrali; Maddur, Mohan S.; Stephen-Victor, Emmanuel; Gilardin, Laurent; Lecerf, Maxime; Bruneval, Patrick; Mouthon, Luc; Benveniste, Olivier; Kaveri, Srini V.; Bayry, Jagadeesh

    2014-01-01

    Intravenous immunoglobulin (IVIg) is used in the therapy of various autoimmune and inflammatory diseases. Recent studies in experimental models propose that anti-inflammatory effects of IVIg are mainly mediated by α2,6-sialylated Fc fragments. These reports further suggest that α2,6-sialylated Fc fragments interact with DC-SIGN+ cells to release IL-33 that subsequently expands IL-4-producing basophils. However, translational insights on these observations are lacking. Here we show that IVIg therapy in rheumatic patients leads to significant raise in plasma IL-33. However, IL-33 was not contributed by human DC-SIGN+ dendritic cells and splenocytes. As IL-33 has been shown to expand basophils, we analyzed the proportion of circulating basophils in these patients following IVIg therapy. In contrast to mice data, IVIg therapy led to basophil expansion only in two patients who also showed increased plasma levels of IL-33. Importantly, the fold-changes in IL-33 and basophils were not correlated and we could hardly detect IL-4 in the plasma following IVIg therapy. Thus, our results indicate that IVIg-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients. Hence, IL-33 and basophil-mediated anti-inflammatory mechanism proposed for IVIg might not be pertinent in humans. PMID:25012067

  15. Incorporation of intravenously injected albumin, immunoglobulin G, and fibrinogen in guinea pig megakaryocyte granules.

    PubMed Central

    Handagama, P J; Shuman, M A; Bainton, D F

    1989-01-01

    In a previous study we provide evidence for a circuitous pathway by which circulating plasma proteins enter megakaryocyte granules by an endocytic mechanism and are returned to the circulation in platelets (1987. Proc. Natl. Acad. Sci. USA. 84:861-865). Horseradish peroxidase (40,000 mol wt) was injected into guinea pigs and its uptake into megakaryocyte organelles examined by electron microscopy and cytochemistry. In the present study we tested the ability of guinea pig megakaryocytes to take up intravenously injected albumin, IgG, and fibrinogen. We used two types of proteins to study the endocytic pathway: (a) heterologous human proteins, which were detected immunohistochemically using antibodies that do not crossreact with the native guinea pig counterparts; and (b) human and guinea pig proteins labeled with the small (250 mol wt), inert molecule, biotin, which were detected using an antibody against biotin. We detected all three of the injected proteins in bone marrow megakaryocytes in patterns identical to those of native counterparts. The injected protein consistently appeared in platelets 24 h later and was secreted in response to thrombin. We conclude that there are at least two mechanisms by which guinea pig megakaryocyte granules acquire proteins (a) endogenous synthesis, as demonstrated by others, and (b) endocytosis of plasma proteins synthesized by other types of cells. Images PMID:2738161

  16. Intravenous tPA Therapy Does Not Worsen Acute Intracerebral Hemorrhage in Mice

    PubMed Central

    Foerch, Christian; Rosidi, Nathanael L.; Schlunk, Frieder; Lauer, Arne; Cianchetti, Flor A.; Mandeville, Emiri; Arai, Ken; Yigitkanli, Kazim; Fan, Xiang; Wang, Xiaoying; van Leyen, Klaus; Steinmetz, Helmuth; Schaffer, Chris B.; Lo, Eng H.

    2013-01-01

    Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy. PMID:23408937

  17. Intravenous tPA therapy does not worsen acute intracerebral hemorrhage in mice.

    PubMed

    Foerch, Christian; Rosidi, Nathanael L; Schlunk, Frieder; Lauer, Arne; Cianchetti, Flor A; Mandeville, Emiri; Arai, Ken; Yigitkanli, Kazim; Fan, Xiang; Wang, Xiaoying; van Leyen, Klaus; Steinmetz, Helmuth; Schaffer, Chris B; Lo, Eng H

    2013-01-01

    Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy.

  18. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine.

    PubMed

    Seder, Robert A; Chang, Lee-Jah; Enama, Mary E; Zephir, Kathryn L; Sarwar, Uzma N; Gordon, Ingelise J; Holman, LaSonji A; James, Eric R; Billingsley, Peter F; Gunasekera, Anusha; Richman, Adam; Chakravarty, Sumana; Manoj, Anita; Velmurugan, Soundarapandian; Li, MingLin; Ruben, Adam J; Li, Tao; Eappen, Abraham G; Stafford, Richard E; Plummer, Sarah H; Hendel, Cynthia S; Novik, Laura; Costner, Pamela J M; Mendoza, Floreliz H; Saunders, Jamie G; Nason, Martha C; Richardson, Jason H; Murphy, Jittawadee; Davidson, Silas A; Richie, Thomas L; Sedegah, Martha; Sutamihardja, Awalludin; Fahle, Gary A; Lyke, Kirsten E; Laurens, Matthew B; Roederer, Mario; Tewari, Kavita; Epstein, Judith E; Sim, B Kim Lee; Ledgerwood, Julie E; Graham, Barney S; Hoffman, Stephen L

    2013-09-20

    Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine--composed of attenuated, aseptic, purified, cryopreserved PfSPZ--was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 10(5) PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.

  19. Intravenous Artesunate: The New Generation of Lifesaving Treatment for Severe Malaria in the Warfighter

    DTIC Science & Technology

    2006-11-01

    and oral antimalarials are given to kill any remaining parasites. Oral antimalarials typically used include quinine , mefloquine, sulphadoxine...pyrimethamine, or, more recently, oral artemisinins. Parenteral agents available for the worldwide treatment of severe malaria are primarily quinine ...intramuscular or intravenous) or quinidine (intravenous). Despite appropriate medical care and prior parenteral quinine treatment, mortality from

  20. Development of an Intravenous Therapy Module for Second Year Registered Nursing Students.

    ERIC Educational Resources Information Center

    Balint, Marilyn

    A study aimed at developing an intravenous therapy module for second-year registered nursing students is described in this practicum report. The report's five chapters define the underlying problem and purpose of the study; discuss the history of intravenous therapy and the significance of the module to the host institution; review the relevant…

  1. Efficacy of Intravenous and Endotracheal Epinephrine during Neonatal Cardiopulmonary Resuscitation in the Delivery Room.

    PubMed

    Halling, Cecilie; Sparks, John E; Christie, Lucy; Wyckoff, Myra H

    2017-03-10

    A retrospective examination is presented of intravenous vs a lower (0.03 mg/kg) and higher (0.05 mg/kg) dose of endotracheal epinephrine during delivery room cardiopulmonary resuscitation. Repeated dosing of intravenous and endotracheal epinephrine is needed frequently for successful resuscitation. Research regarding optimal dosing for both routes is needed critically.

  2. 45 CFR 96.126 - Capacity of treatment for intravenous substance abusers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.126 Capacity of treatment... programs that receive funding under the grant and that treat individuals for intravenous substance abuse to... 45 Public Welfare 1 2014-10-01 2014-10-01 false Capacity of treatment for intravenous...

  3. 45 CFR 96.126 - Capacity of treatment for intravenous substance abusers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.126 Capacity of treatment... programs that receive funding under the grant and that treat individuals for intravenous substance abuse to... 45 Public Welfare 1 2013-10-01 2013-10-01 false Capacity of treatment for intravenous...

  4. 45 CFR 96.126 - Capacity of treatment for intravenous substance abusers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.126 Capacity of treatment... programs that receive funding under the grant and that treat individuals for intravenous substance abuse to... 45 Public Welfare 1 2011-10-01 2011-10-01 false Capacity of treatment for intravenous...

  5. 45 CFR 96.126 - Capacity of treatment for intravenous substance abusers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ADMINISTRATION BLOCK GRANTS Substance Abuse Prevention and Treatment Block Grant § 96.126 Capacity of treatment... programs that receive funding under the grant and that treat individuals for intravenous substance abuse to... 45 Public Welfare 1 2012-10-01 2012-10-01 false Capacity of treatment for intravenous...

  6. Effect of naloxone on intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy

    PubMed Central

    Zheng, Jun; Han, Wen; Han, Xiao-Dong; Ma, Xiao-Yuan; Zhang, Pengbo

    2016-01-01

    Abstract This study aims to evaluate the effect of naloxone on intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy under total intravenous anesthesia. A total of 90 patients, who underwent intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy under total intravenous anesthesia, were included into this study. All patients were randomly divided into 3 groups (each group, n=30): naloxone group (naloxone+fentanyl), tropisetron group (tropisetron+fentanyl), and fentanyl group (fentanyl). Patients in each group were given a corresponding dose of naloxone. Postoperative analgesia effect and the incidence of side effects such as nausea and vomiting were observed. Small doses of naloxone or tropisetron combined with fentanyl used for intravenous patient-controlled analgesia can significantly reduce the incidence of nausea and vomiting. Six hours after surgery, visual analogue scale (VAS) scores were significantly lower in patients that underwent intravenous patient-controlled analgesia using low-dose naloxone combined with fentanyl compared with patients who received fentanyl alone; however, the postoperative analgesic effect of tropisetron was not observed. Compared with the combination of tropisetron and fentanyl, low-dose naloxone combined with fentanyl can obviously reduce the incidence of nausea and vomiting in patients who underwent intravenous patient-controlled analgesia after laparoscopic cholecystectomy, and enhance the analgesic effect of fentanyl 6 hours after surgery. Low-dose naloxone can reduce the incidence of nausea and vomiting in patients who underwent laparoscopic cholecystectomy under total intravenous anesthesia, and exhibits a certain synergic analgesic effect. PMID:27902584

  7. Effect of naloxone on intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy.

    PubMed

    Zheng, Jun; Han, Wen; Han, Xiao-Dong; Ma, Xiao-Yuan; Zhang, Pengbo

    2016-11-01

    This study aims to evaluate the effect of naloxone on intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy under total intravenous anesthesia.A total of 90 patients, who underwent intravenous fentanyl patient-controlled analgesia after laparoscopic cholecystectomy under total intravenous anesthesia, were included into this study. All patients were randomly divided into 3 groups (each group, n=30): naloxone group (naloxone+fentanyl), tropisetron group (tropisetron+fentanyl), and fentanyl group (fentanyl). Patients in each group were given a corresponding dose of naloxone. Postoperative analgesia effect and the incidence of side effects such as nausea and vomiting were observed.Small doses of naloxone or tropisetron combined with fentanyl used for intravenous patient-controlled analgesia can significantly reduce the incidence of nausea and vomiting. Six hours after surgery, visual analogue scale (VAS) scores were significantly lower in patients that underwent intravenous patient-controlled analgesia using low-dose naloxone combined with fentanyl compared with patients who received fentanyl alone; however, the postoperative analgesic effect of tropisetron was not observed. Compared with the combination of tropisetron and fentanyl, low-dose naloxone combined with fentanyl can obviously reduce the incidence of nausea and vomiting in patients who underwent intravenous patient-controlled analgesia after laparoscopic cholecystectomy, and enhance the analgesic effect of fentanyl 6 hours after surgery.Low-dose naloxone can reduce the incidence of nausea and vomiting in patients who underwent laparoscopic cholecystectomy under total intravenous anesthesia, and exhibits a certain synergic analgesic effect.

  8. A case of polymicrobial infective endocarditis involving Neisseria mucosa occurring in an intravenous drug abuser.

    PubMed

    Giles, M W; Andrew, J H; Tellus, M M

    1988-12-01

    The incidence of polymicrobial endocarditis has increased markedly in recent years, in association with the increasing level of abuse of intravenous drugs. Neisseria mucosa, an upper respiratory tract commensal, is a rare cause of infective endocarditis. We report the first case of polymicrobial infective endocarditis involving Neisseria mucosa occurring in an intravenous drug abuser.

  9. Total intravenous anaesthesia. A technique based on alphaxalone/alphadolone and pentazocine.

    PubMed

    Jago, R H; Restall, J

    1977-10-01

    Two hundred and eight patients were anaesthetised using incremental doses of intravenous alphaxalone/alphadolone (Althesin). Analgesia was provided by supplements of pentazocine, which also helped eliminate the excessive movements associated with pure Althesin anaesthesia. This is a total intravenous technique and consequently eliminates the problem of atmospheric pollution. It provides adequate anaesthesia for most minor surgical procedures.

  10. Evaluation of intravenous anthrax immune globulin for treatment of inhalation anthrax.

    PubMed

    Mytle, Nutan; Hopkins, Robert J; Malkevich, Nina V; Basu, Subhendu; Meister, Gabriel T; Sanford, Daniel C; Comer, Jason E; Van Zandt, Kristopher E; Al-Ibrahim, Mohamed; Kramer, William G; Howard, Cris; Daczkowski, Nancy; Chakrabarti, Ajoy C; Ionin, Boris; Nabors, Gary S; Skiadopoulos, Mario H

    2013-11-01

    Bacillus anthracis toxins can be neutralized by antibodies against protective antigen (PA), a component of anthrax toxins. Anthrivig (human anthrax immunoglobulin), also known as AIGIV, derived from plasma of humans immunized with BioThrax (anthrax vaccine adsorbed), is under development for the treatment of toxemia following exposure to anthrax spores. The pharmacokinetics (PK) of AIGIV was assessed in naive animals and healthy human volunteers, and the efficacy of AIGIV was assessed in animals exposed via inhalation to aerosolized B. anthracis spores. In the clinical study, safety, tolerability, and PK were evaluated in three dose cohorts (3.5, 7.1, and 14.2 mg/kg of body weight of anti-PA IgG) with 30 volunteers per cohort. The elimination half-life of AIGIV in rabbits, nonhuman primates (NHPs), and humans following intravenous infusion was estimated to be approximately 4, 12, and 24 days, respectively, and dose proportionality was observed. In a time-based treatment study, AIGIV protected 89 to 100% of animals when administered 12 h postexposure; however, a lower survival rate of 39% was observed when animals were treated 24 h postexposure, underscoring the need for early intervention. In a separate set of studies, animals were treated on an individual basis upon detection of a clinical sign or biomarker of disease, namely, a significant increase in body temperature (SIBT) in rabbits and presence of PA in the serum of NHPs. In these trigger-based intervention studies, AIGIV induced up to 75% survival in rabbits depending on the dose and severity of toxemia at the time of treatment. In NHPs, up to 33% survival was observed in AIGIV-treated animals. (The clinical study has been registered at ClinicalTrials.gov under registration no. NCT00845650.).

  11. Peripheral intravenous and central catheter algorithm: a proactive quality initiative.

    PubMed

    Wilder, Kerry A; Kuehn, Susan C; Moore, James E

    2014-12-01

    Peripheral intravenous (PIV) infiltrations causing tissue damage is a global issue surrounded by situations that make vascular access decisions difficult. The purpose of this quality improvement project was to develop an algorithm and assess its effectiveness in reducing PIV infiltrations in neonates. The targeted subjects were all infants in our neonatal intensive care unit (NICU) with a PIV catheter. We completed a retrospective chart review of the electronic medical record to collect 4th quarter 2012 baseline data. Following adoption of the algorithm, we also performed a daily manual count of all PIV catheters in the 1st and 2nd quarters 2013. Daily PIV days were defined as follows: 1 patient with a PIV catheter equals 1 PIV day. An infant with 2 PIV catheters in place was counted as 2 PIV days. Our rate of infiltration or tissue damage was determined by counting the number of events and dividing by the number of PIV days. The rate of infiltration or tissue damage was reported as the number of events per 100 PIV days. The number of infiltrations and PIV catheters was collected from the electronic medical record and also verified manually by daily assessment after adoption of the algorithm. To reduce the rate of PIV infiltrations leading to grade 4 infiltration and tissue damage by at least 30% in the NICU population. Incidence of PIV infiltrations/100 catheter days. The baseline rate for total infiltrations increased slightly from 5.4 to 5.68/100 PIV days (P = .397) for the NICU. We attributed this increase to heightened awareness and better reporting. Grade 4 infiltrations decreased from 2.8 to 0.83/100 PIV catheter days (P = .00021) after the algorithm was implemented. Tissue damage also decreased from 0.68 to 0.3/100 PIV days (P = .11). Statistical analysis used the Fisher exact test and reported as statistically significant at P < .05. Our findings suggest that utilization of our standardized decision pathway was instrumental in providing guidance for

  12. Pharmacokinetics of melamine in pigs following intravenous administration.

    PubMed

    Baynes, Ronald E; Smith, Geof; Mason, Sharon E; Barrett, Erica; Barlow, Beth M; Riviere, Jim E

    2008-03-01

    Melamine-contaminated pet food was recently added as a supplement to livestock feed. There is little or no information concerning the pharmacokinetics of melamine in livestock, and the aim of this study was to obtain pharmacokinetic parameters for this contaminant in pigs. Melamine was administered intravenously to five weanling pigs at a dose of 6.13 mg/kg and plasma samples were collected over 24 h, extracted for melamine, and then analyzed by HPLC-UV. The data was shown to best fit a one-compartment model with melamine's half-life of 4.04 (+/- 0.37) h, clearance of 0.11 (+/- 0.01) L/h/kg, and volume of distribution of 0.61 (+/- 0.04) L/kg. These data are comparable to the only mammalian study in rats and suggests that melamine is readily cleared by the kidney and there is unlikely to be significant tissue binding. Further tissue residue studies are required to assess the depletion kinetics of this contaminant in the pig which will determine whether residue levels in the kidney should be of public health concern if pigs were exposed to a similar dose.

  13. Safety of intravenous iron use in chronic kidney disease

    PubMed Central

    Kalra, Philip A.; Bhandari, Sunil

    2016-01-01

    Purpose of review Iron deficiency anaemia (IDA) is common and associated with fatigue, reduced quality of life and poorer clinical outcomes. Treatment with oral iron is often inadequate and international guidelines recommend intravenous (i.v.) iron as the preferred option for the treatment of IDA in certain clinical situations. In this review, we assess the safety of using i.v. iron with a particular focus on patients with chronic kidney disease. Recent findings Recent publications have raised safety concerns regarding the incidence of serious reactions accompanying i.v. infusion, as well as the subsequent risk of infections and cardiovascular events. Methodological flaws influence the interpretation of these data that lack evidence from the use of modern irons. The latter have been investigated in several randomized control trials. Summary There is a need for better understanding and definition of the nature of i.v. iron reactions, as many are nonserious infusion reactions rather than true anaphylaxis. Retrospective identification of anaphylaxis is difficult and we suggest the importance of reanalysing data using fatalities or standardized terms as outcome measures. With the exception of high molecular weight iron dextran, serious or life-threatening reactions are rare with the use of i.v. irons, and they can be used safely for the treatment of IDA. PMID:27557350

  14. The Production Processes and Biological Effects of Intravenous Immunoglobulin

    PubMed Central

    Barahona Afonso, Ana Filipa; João, Cristina Maria Pires

    2016-01-01

    Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it can stimulate certain sub-populations of T cells with effects on T cell proliferation, survival and function in situations of lymphopenia. These results present a novel and considerable impact of intravenous immunoglobulin (IVIg) treatment in situations of severe lymphopenia, a situation that can occur in cancer patients after chemo and radiotherapy treatments. In this review paper the established and experimental role of polyclonal immunoglobulin will be presented and discussed as well as the manufacturing processes involved in their production. PMID:27005671

  15. Pharmacokinetics of florfenicol after intravenous and intramuscular dosing in llamas.

    PubMed

    Pentecost, Rebecca L; Niehaus, Andrew J; Werle, Nick A; Lakritz, Jeffrey

    2013-10-01

    Florfenicol, is a broad spectrum antimicrobial agent with wide tissue distribution commonly used to treat camelids. To address the lack of drug disposition data for florfenicol in llamas, we evaluated the pharmacokinetics after 20mg/kg intravenous (i.v.) and intramuscular (i.m.) dosing. Serum concentrations were determined using a HPLC-UV assay and pharmacokinetic analysis was conducted using non-compartmental analysis. Following i.v. injection, systemic clearance and Vdss in llamas were 4.6 mL/min/kg and 737 mL/kg, respectively. Mean residence time after i.v. dosing was 3h. After i.m. injection, florfenicol was rapidly absorbed, with Cmax concentrations being 3.2 μg/mL at 0.5h, mean residence time was 15 h, mean absorption time was 12h and absolute bioavailability of florfenicol after i.m. injection was 63%. The prolonged absorption of florfenicol after i.m. administration suggests the apparent HL_λz reflects the absorption process rather than elimination of the drug. Florfenicol administration was not associated with adverse reactions after dosing by either route. Serum florfenicol concentrations remained >1.0 μg/mL for 12h after i.m. administration. For susceptible pathogens, once daily dosing of 20mg/kg body weight appears appropriate.

  16. Case report: acute renal failure after administering intravenous immunoglobulin.

    PubMed

    Graumann, Aaron; Zawada, Edward T

    2010-03-01

    We report the case of an 87-year-old white woman with myasthenia gravis who presented with nausea, shortness of breath, azotemia, and hyperkalemia shortly after completing a course of intravenous immunoglobulin (IVIG). She had been receiving monthly transfusions of IVIG, but this time had received daily infusions for 5 days rather than 1 day. She had received this same dose in the past without incident. Her history was significant for coronary artery disease, atrial fibrillation, deep venous thrombosis, pulmonary embolism, chronic steroid use, and recurrent urinary tract infection. On examination, she was slightly confused, mildly dehydrated, had a grade II systolic ejection murmur along the upper left sternal border, had bilateral and symmetric mild weakness of the upper and lower extremities, and exhibited mild edema of the lower extremities. Before transfer from the emergency room, she was found to have an elevated serum urea nitrogen and creatinine of 55 and 5.8 mg/dL (19.6 mmol/L and 512.7 micromol/L, respectively). Creatinine 8 days earlier was 0.9 mg/dL (79.6 micromol/L). The hospital course of the acute renal failure is presented with a review of the literature on cases of acute renal failure after IVIG.

  17. Intravenous and oral amiodarone for arrhythmias in children.

    PubMed Central

    Bucknall, C A; Keeton, B R; Curry, P V; Tynan, M J; Sutherland, G R; Holt, D W

    1986-01-01

    Oral amiodarone was administered to 30 children (aged one week to 14 years) for treatment of resistant or life threatening tachycardias. Five children received initial intravenous medication. The mean duration of oral treatment ranged from two weeks to 64 months (mean 23 months). Infants required a higher oral dose than older children when this was calculated on the basis of body weight but not when it was calculated on the basis of body surface area, indicating that the prescribed dose of amiodarone for infants should be calculated on the basis of body surface area. Although plasma concentrations of amiodarone were similar in infants and children, the plasma concentration of the metabolite desethylamiodarone was lower in infants. The arrhythmias were effectively controlled, by amiodarone alone in 19 and by amiodarone in combination with other drugs in nine children; amiodarone was ineffective in the remaining two children. Unwanted effects were common but were not significantly related to the dose, duration of treatment, or plasma concentration of amiodarone when group results were analysed. Grey facial skin pigmentation developed in two patients who received high cumulative doses of amiodarone and in whom plasma concentrations of amiodarone were high. Four children with biochemical hepatic dysfunction had high plasma concentrations of amiodarone and a further four children who experienced sleep disturbance had required high doses of amiodarone. Images Fig 1 Fig 2 PMID:3756044

  18. Infective endocarditis in an HIV-infected intravenous drug user.

    PubMed

    Mėlinytė, Karolina; Savickaitė, Jurgita; Rekienė, Daiva Emilija; Naudžiūnas, Albinas; Burkauskienė, Aušra; Jankauskienė, Laima

    2015-10-01

    Infective endocarditis is a common complication among injecting drug users. Disease risk among these patients is increased by the spread of HIV infection. In the following article, we discuss the exceptional clinical presentation of a 28-year-old patient who used intravenous drugs (heroin) for 10 years, had been infected with HIV for seven years and as a complication had developed Staphylococcus aureus infective endocarditis. The patient came to the hospital in serious condition, complaining of bodily pain, swelling of the legs and general weakness. During hospitalization, besides infective endocarditis, she was also diagnosed with anemia, toxic hepatitis, renal failure, ascites, sepsis, and pneumonia. A completely disrupted tricuspid valve, damaged aortic valve, and fibrosis of the mitral valve were detected. Echocardiographic and radiologic data showed that the patient's condition continued to deteriorate day by day, with significant progression of heart failure, ejection fraction decreasing from 45% to 10%, and development of myocarditis, hydrothorax and pericarditis. However, this progressive worsening of the patient's condition ceased when vancomycin was administered. To the authors' knowledge, this is the first such case described in the literature in which significant improvement was observed despite the patient's complex condition with associated complications.

  19. Formulation, stability and degradation kinetics of intravenous cinnarizine lipid emulsion.

    PubMed

    Shi, Shuai; Chen, Hao; Cui, Yue; Tang, Xing

    2009-05-21

    Cinnarizine was loaded in the lipid emulsion to develop an intravenous formulation with good physical and chemical stability. High-pressure homogenization was used to prepare the lipid emulsion. The factors influencing the stability of cinnarizine lipid emulsion, such as different drug loading methods, pH, temperature, sterilization methods and sterilization time were monitored by high-performance liquid chromatograph. The degradation of cinnarizine in aqueous solution and lipid emulsion both followed apparent first-order kinetics. A possible degradation mechanism was postulated by the bell-shaped pH-rate profile of cinnarizine. Localization of the drug in the interfacial lecithin layer significantly improved the chemical stability of cinnarizine and its stabilizing mechanism was thoroughly discussed and proved. The activation energy of cinnarizine in lipid emulsion was calculated to be 51.27 kJ/mol which was similar to that in aqueous solution. This indicates that the stabilizing effect of the drug carrier on cinnarizine was not an alteration of the degradation reaction. In addition, shelf-life of cinnarizine in lipid emulsion was estimated to be 1471.6 days at 4 degrees C, which is much longer compared with 19.8 days in aqueous solution. The final products were stable enough to resist a 121 degrees C rotating steam sterilization for 15 min.

  20. Premixed intravenous admixtures: a positive development for hospital pharmacy.

    PubMed

    Lee, H E

    1983-06-01

    The development of premixed intravenous admixtures is reviewed in a historical context, and its effects on hospital pharmacy practice are discussed. As pharmaceutical manufacturers introduce more i.v. medications in ready-to-use containers, the same complaints that were voiced by pharmacists about unit dose packaging and ready-to-dispense tablets and capsules are being aired. But premixed i.v. admixtures are a logical extension of the basic unit dose principle of providing a readily identifiable and ready-to-administer dose. The time and cost savings these products offer are needed in hospital pharmacies. Some of the disadvantages of these products--including storage and freezer space and multiplicity of administration systems--are overcome by proper planning and education of personnel. If fewer personnel are now needed to prepare i.v. admixtures, then those personnel should be used to improve patient care in other ways. The use of premixed i.v. admixtures is a positive technological advance in drug packaging. Its advantages outweight its disadvantages, and it will soon be become the universally accepted form of i.v. drug packaging.

  1. Mechanisms of action of intravenous immunoglobulin in inflammatory muscle disease.

    PubMed

    Quick, Adam; Tandan, Rup

    2011-06-01

    Intravenous immunoglobulin (IVIG) is a unique immune-modulating therapy that has a wide range of effects on the immune system at multiple levels. This allows it to be used successfully in a variety of immune-mediated, systemic, and neurological disorders, including the inflammatory myopathies. It is likely that the specific action of IVIG varies depending on the underlying pathogenesis of a given disease. In dermatomyositis (DM), IVIG has been shown to diminish the activity of complement and deposition of membrane attack complex on capillaries and muscle fibers, the expression of adhesion molecules, and cytokine production. IVIG also appears to modify gene expression in the muscle of DM patients. The mechanism by which IVIG affects muscle in polymyositis and inclusion body myositis has not been well-studied. However, it may work via suppression of T-cell activation (including cytotoxic T cells) and migration into muscle tissue and alterations in cytokine production. IVIG generally yields the greatest therapeutic benefit in DM and is often of marginal utility in inclusion body myositis. It is generally considered as second-line or adjunctive therapy in the inflammatory myopathies.

  2. Evaluation of two sterility testing methods for intravenous admixtures.

    PubMed

    Condella, F; Eichelberger, K; Foote, L C; Griffin, R E

    1980-06-01

    The Addi-Chek Quality Control System (Millipore Corporation) and Ivex-2 Filterset (Abbott Laboratories) were evaluated to determine their effectiveness, applicability, and cost as part of a pharmacy quality-control program. Each method was tested using 50 solutions, 25 of which had been contaminated by inoculation with one of five micro-organisms; the other 25 solutions were used as controls. Aseptic technique was used, and procedures were carried out in a laminar air flow hood. Contaminated solutions were blinded from the person performing the tests. Addi-Chek detected contamination in all the inoculated solutions and in three of the uninoculated solutions. The latter may have been a result of adventitious contamination during the testing procedure. Ivex-2 detected contamination in 24 of the 25 inoculated solutions; no other contamination was found. The effectiveness of the methods in detecting low-level microbial contamination appears comparable. Both methods have been shown to be useful in the pharmacy setting, but Ivex-2 could be used to test for contamination when used as an in-line filter at the patient level. Ivex-2 is less expensive and warrants further evaluation in monitoring for microbial contamination during preparation and administration of intravenous solutions.

  3. Microbiologic quality assurance for intravenous admixtures in a small hospital.

    PubMed

    Doss, H L; James, J D; Killough, D M; Snodgrass, G L

    1982-05-01

    A simple, inexpensive method for end-product testing of intravenous admixtures for microbial contamination was developed and tested by challenging the system with low levels of microbial contamination. The 16-step procedure for testing i.v. admixtures for microbial contamination used total-sample membrane filtration A 0.2-micrometers Nalgene filter unit was used; the entire contents of randomly selected admixtures were to be filtered and discarded under the procedure. Filters were incubated on sheep-blood agar plates for 48 hours at 35 degrees C. Low concentrations (Klebsiella pneumoniae and Pseudomonas aeruginosa were used to contaminate admixtures deliberately to challenge the system. Seventy-two solutions were contaminated with each microbe; 72 other solutions were inoculated with sterile 0.9% sodium chloride; and 72 uninoculated solutions served as controls. Filtration was performed on a laboratory bench to prevent contamination of the laminar-flow hood. In deliberately contaminated solutions, a mean of 82% of inoculated organisms was isolated by membrane filtration. Five instances of adventitious contamination were noted among the 288 samples; these occurred across all experimental groups. Cost per sample was $4-5. This system can be used by hospital pharmacists to produce documentation of quality assurance that will be acceptable in terms of cost, simplicity, and accuracy.

  4. Cefoxitin sodium compatibility with intravenous infusions and additives.

    PubMed

    O'Brien, M J; Portnoff, J B; Cohen, E M

    1979-01-01

    The compatibility and stability of cefoxitin sodium in solution with a series of frequently used intravenous infusion fluids and injectable additives were studied. Cefoxitin sodium's stability in various solutions was measured by ultraviolet spectrophotometry, iodometry, thin-layer chromatography, high-pressure liquid chromatography, ion-exchange chromatography and microbiological assay. Cefoxitin sodium was shown to maintain 90% of its initial concentration in aqueous solution for 40 hours at room temperature (25 C) and about 30 days at 5 C. The stability of cefoxitin sodium in common i.v. infusion fluids was independent of the concentrations (1 mg/ml to 400 mg/ml) and containers used, and was retained after 30 weeks storage at -20 C. Similar stability patterns were demonstrated for cefoxitin sodium in protein hydrolysate solutions and multivitamin formulations. Cefoxitin sodium was chemically and visually compatible with amikacin sulfate, gentamicin sulfate, kanamycin sulfate and tobramycin sulfate when admixed with normal saline or 5% dextrose in water injections. Cefoxitin sodium (397 mg/ml) in 0.5% lidocaine hydrochloride was stable after 26 weeks of storage at -20 C. Sodium cefoxitin is compatible with a wide variety of commonly used infusion solutions. Its stability is independent of concentration or pH within the ranges studied, and of types of common containers.

  5. IMMEDIATE DISCONTINUATION OF INTRAVENOUS FLUIDS AFTER COMMON SURGICAL PROCEDURES

    PubMed Central

    Al-Awad, Naif I.; Wosomu, Lade; Al Hassanin, Emad A.W.; Al-Mulhim, Abdulmohsen A.; Adu-Gyamfi, Yaw; Shawan, Saad M.; Abdulhadi, Maha S.

    2000-01-01

    Background: Intravenous (IV) fluids and nasogastric (MG) intubation can be discarded safely in some abdominal operations, but this practice seems rare in our community. Setting: A University teaching hospital in Eastern Saudi Arabia. Aims: To determine the feasibility of the practice in our setting and increase clinicians’ awareness of it and encourage its general adoption. Method: A prospective verification study in consecutive ASA Classes I and II adult patients scheduled for four commonly performed operations. End Points: The practice was considered successful if the patient accepted early oral fluids and did not require re-insertion of IV line. Results: The operations studied were appendicectomy (44), laparoscopic cholecystectomy (35), herniorrhaphy (19) and diagnostic laparoscopy (2). The patients’ mean age was 34.1 years (range 14 to 68); 60% were males. The overall success rate was 98%. Thus postoperative IV fluids proved to be unnecessary in these patients; cost savings were achieved and treating teams were freed to focus on other patients who truly required IV fluids. Conclusions: In our setting also, routine IV fluids are unnecessary and can be discarded safely after appendecectomy, cholecystectomy and herniorrhaphy in adults. PMID:23008615

  6. Portable Intravenous Fluid Production Device for Ground Use

    NASA Technical Reports Server (NTRS)

    Scarpa, Philip J.; Scheuer, Wolfgang K.

    2012-01-01

    There are several medical conditions that require intravenous (IV) fluids. Limitations of mass, volume, storage space, shelf-life, transportation, and local resources can restrict the availability of such important fluids. These limitations are expected in long-duration space exploration missions and in remote or austere environments on Earth. Current IV fluid production requires large factory-based processes. Easy, portable, on-site production of IV fluids can eliminate these limitations. Based on experience gained in developing a device for spaceflight, a ground-use device was developed. This design uses regular drinking water that is pumped through two filters to produce, in minutes, sterile, ultrapure water that meets the stringent quality standards of the United States Pharmacopeia for Water for Injection (Total Bacteria, Conductivity, Endotoxins, Total Organic Carbon). The device weighs 2.2 lb (1 kg) and is 10 in. long, 5 in. wide, and 3 in. high (.25, 13, and 7.5 cm, respectively) in its storage configuration. This handheld device produces one liter of medical-grade water in 21 minutes. Total production capacity for this innovation is expected to be in the hundreds of liters.

  7. Oxidative effect of several intravenous iron complexes in the rat.

    PubMed

    Bailie, George R; Schuler, Catherine; Leggett, Robert E; Li, Hsin; Li, Hsin-Dat; Patadia, Hiten; Levin, Robert

    2013-06-01

    The objective of this study was to compare the oxidative stress induced in rat internal organs by the administration of the following clinically used intravenous (IV) iron (Fe) containing compounds: iron sucrose (IS), iron dextran (ID), ferric carboxymaltose and ferumoxytol. Groups of six adult rats received 1 mg/kg of each compound weekly for 5 doses. Seven days following the last dose, animals were euthanized and tissue samples of heart, lung, liver, and kidney were obtained, washed in warmed saline and frozen under liquid nitrogen and stored at -80 °C for analysis for nitrotyrosine (NT) and dinitro phenyl (DNP) as markers of oxidative stress. All tissues showed a similar pattern of oxidative stress. All Fe products stimulated an increase in the tissue concentration of both NT and DNP. In general, DNP was stimulated significantly less than NT except for IS. DNP was stimulated to an equal degree except for ID where NT was significantly higher than the NT concentrations in all other Fe compounds. ID produced over 10-fold the concentration of NT than any other Fe. IV Fe compounds present a risk of oxidative stress to a variety of internal organs. However, we found that IS was the least damaging and ID was the worst.

  8. Intravenous Leiomyomatosis with Intracardiac Extension: Echocardiographic Study and Literature Review

    PubMed Central

    Li, Rongjuan; Shen, Yanguang; Sun, Yan; Zhang, Chuanchen; Yang, Jiao; Su, Ruijuan; Jiang, Bo

    2014-01-01

    Uterine leiomyomatosis is a common disease in women; however, intravenous leiomyomatosis with intracaval and intracardiac tumor extension is rare. We sought to analyze the clinical and echocardiographic features of intracardiac leiomyomatosis. From January 2003 through July 2012, 7 women (age range, 24–59 yr) underwent surgical resection of histopathologically diagnosed intracardiac leiomyomas at our hospital. Most of the patients had histories of hysterectomy or uterine leiomyoma. We retrospectively analyzed their preoperative echocardiograms. We found that the tumors had no stalks, did not adhere to the wall of the right side of the heart, were highly mobile, and moved back and forth in the right atrium near the tricuspid orifice. All tumors originated from the inferior vena cava and had borders well demarcated from that structure's wall. Most of the masses extended into the inferior vena cava and right atrium through the right internal and common iliac veins. Computed tomograms revealed pelvic tumors and contiguous filling defects in 6 patients. When echocardiograms reveal a right-sided cardiac mass that originates from the inferior vena cava, particularly in women who have a history of hysterectomy or uterine leiomyoma, intracardiac leiomyomatosis should be suspected. If the mass has no stalk and freely moves within the inferior vena cava and right-sided cardiac chambers without attachment to the endothelial surface or endocardium, intracardiac leiomyomatosis should be diagnosed. We discuss our findings and briefly review the relevant medical literature. PMID:25425982

  9. Mortality of intravenous drug users in Rome: a cohort study.

    PubMed Central

    Perucci, C A; Davoli, M; Rapiti, E; Abeni, D D; Forastiere, F

    1991-01-01

    A historical cohort study was carried out in Rome to examine overall and cause-specific mortality among intravenous drug users (IVDUs). A total of 4200 IVDUs (3411 men and 789 women) enrolled in methadone treatment centers between 1980 and 1988 were studied. There were 239 deaths during the follow-up period. The overall SMR was 10.10 in the entire cohort (95% confidence interval, 8.86-11.47), 9.30 in males and 18.07 in females. A large excess of mortality in both sexes was found for infectious, circulatory, respiratory, and digestive diseases as well as for violence, overdose, AIDS, and unknown or ill-defined causes. Tumors and suicide were excessive only in males. Deaths due to drug overdose, violence or trauma, and cirrhosis accounted for 63.6%, AIDS for 7.1%, endocarditis and other bacterial infections for 7.1%, and neoplasms for 3.8% of total mortality. These findings document serious health consequences of drug abuse in Italy. PMID:1656799

  10. Effect of intravenous nutrient infusions on food intake in rats.

    PubMed

    Walls, E K; Koopmans, H S

    1989-06-01

    To assess the effect of gut signals on food intake two types of nutrients were infused intravenously for 17.5 hours in 17 hour fed rats. In the first experiment a solution of 25% d-glucose and 4.25% amino acids (Travasol) was infused at levels of 26 and 52 kcal/day for two consecutive four-day periods. During infusion periods, food intake was reduced from saline baseline levels by 18.9 +/- 1.7 and 34.8 +/- 1.8 kcal/day, respectively. This represents an oral intake reduction of approximately 70% of the infused calories. In contrast, food intake was reduced 17.4 +/- 1.7 kcal/day below saline baseline levels when 40 kcal of Nutralipid were infused. The reduction in food intake was only 43% of the lipid calories infused. These results indicate that infusions of glucose and amino acids are more effective than infusion of fats in inhibiting daily food intake, that gut signals associated with absorption of fat provide important satiety signals and that removal of fat from the bloodstream has relatively little effect on daily food intake.

  11. Cerebral blood flow effects of acute intravenous heroin administration.

    PubMed

    Kosel, Markus; Noss, Roger S; Hämmig, Robert; Wielepp, Peter; Bundeli, Petra; Heidbreder, Rebeca; Kinser, Jane A; Brenneisen, Rudolf; Fisch, Hans-Ulrich; Kayser, Sarah; Schlaepfer, Thomas E

    2008-04-01

    We examined acute effects of intravenous diacetylmorphine (heroin) administration - which induces a characteristic biphasic response: A short rush-sensation associated with intense pleasurable feelings followed by a subjectively different period of euphoria on cerebral blood flow. This was assessed in nine male heroin dependent patients participating in a heroin maintenance program in a setting resembling everyday pattern of heroin abuse. 99mTc-HMPAO was administered 45 s (rush) and 15 min (euphoria) after administration of i.v. heroin and 45 s after administration of saline (placebo). Plasma concentration of diacetylmorphine and its metabolites were measured with high-pressure liquid chromatography (HPLC). Compared to the euphoria condition, rush was associated with blood flow increase in the left posterior cerebellar lobe, left anterior cingulate gyrus and right precuneus. Our results are in line with recent reports indicating that the cerebellum is an important component in functional brain systems subserving sensory and motor integration, learning, modulation of affect, motivation and social behaviour, which all play important roles in reinforcing properties of opioids.

  12. Treatment of Intravenous Leiomyomatosis with Cardiac Extension following Incomplete Resection

    PubMed Central

    Doyle, Mathew P.; Li, Annette; Villanueva, Claudia I.; Peeceeyen, Sheen C. S.; Cooper, Michael G.; Hanel, Kevin C.; Fermanis, Gary G.; Robertson, Greg

    2015-01-01

    Aim. Intravenous leiomyomatosis (IVL) with cardiac extension (CE) is a rare variant of benign uterine leiomyoma. Incomplete resection has a recurrence rate of over 30%. Different hormonal treatments have been described following incomplete resection; however no standard therapy currently exists. We review the literature for medical treatments options following incomplete resection of IVL with CE. Methods. Electronic databases were searched for all studies reporting IVL with CE. These studies were then searched for reports of patients with inoperable or incomplete resection and any further medical treatments. Our database was searched for patients with medical therapy following incomplete resection of IVL with CE and their results were included. Results. All studies were either case reports or case series. Five literature reviews confirm that surgery is the only treatment to achieve cure. The uses of progesterone, estrogen modulation, gonadotropin-releasing hormone antagonism, and aromatase inhibition have been described following incomplete resection. Currently no studies have reviewed the outcomes of these treatments. Conclusions. Complete surgical resection is the only means of cure for IVL with CE, while multiple hormonal therapies have been used with varying results following incomplete resection. Aromatase inhibitors are the only reported treatment to prevent tumor progression or recurrence in patients with incompletely resected IVL with CE. PMID:26783463

  13. Is combined topical with intravenous tranexamic acid superior than topical, intravenous tranexamic acid alone and control groups for blood loss controlling after total knee arthroplasty

    PubMed Central

    Lin, Chunmei; Qi, Yingmei; Jie, Li; Li, Hong-biao; Zhao, Xi-cheng; Qin, Lei; Jiang, Xin-qiang; Zhang, Zhen-hua; Ma, Liping

    2016-01-01

    Abstract Background: The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to evaluate the efficacy and safety of combined topical with intravenous tranexamic acid (TXA) versus topical, intravenous TXA alone or control for reducing blood loss after a total knee arthroplasty (TKA). Methods: In May 2016, a systematic computer-based search was conducted in the PubMed, Embase, Cochrane Library, Web of Science, and Chinese Wanfang database. This systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement criteria. Only patients prepared for primary TKA that administration combined topical with intravenous TXA with topical TXA, intravenous (IV) TXA, or control group for reducing blood loss were included. Eligible criteria were published RCTs about combined topical with intravenous TXA with topical alone or intravenous alone. The primary endpoint was the total blood loss and need for transfusion. The complications of deep venous thrombosis (DVT) were also compiled to assess the safety of combined topical TXA with intravenous TXA. Relative risks (RRs) with 95% CIs were estimated for dichotomous outcomes, and mean differences (MDs) with 95% CIs for continuous outcomes. The Cochrane risk of bias tool was used to appraise a risk of bias. Stata 12.0 software was used for meta-analysis. Results: Fifteen studies involving 1495 patients met the inclusion criteria. The pooled meta-analysis indicated that combined topical TXA with intravenous TXA can reduce the total blood loss compared with placebo with a mean of 458.66 mL and the difference is statistically significant (MD = −458.66, 95% CI: −655.40 to 261.91, P < 0.001). Compared with intravenous TXA, combined administrated TXA can decrease the total blood loss, and the difference is statistically significant (MD = −554.03, 95% CI: −1066.21 to −41.85, P = 0

  14. Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques.

    PubMed

    Freeman, Sara M; Samineni, Sridhar; Allen, Philip C; Stockinger, Diane; Bales, Karen L; Hwa, Granger G C; Roberts, Jeffrey A

    2016-04-01

    Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30 min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.

  15. Systems genetics of intravenous cocaine self-administration in the BXD recombinant inbred mouse panel

    PubMed Central

    Dickson, Price E.; Miller, Mellessa M.; Calton, Michele A.; Bubier, Jason A.; Cook, Melloni N.; Goldowitz, Daniel; Chesler, Elissa J.; Mittleman, Guy

    2015-01-01

    Rationale Cocaine addiction is a major public health problem with a substantial genetic basis for which the biological mechanisms remain largely unknown. Systems genetics is a powerful method for discovering novel mechanisms underlying complex traits, and intravenous drug self-administration (IVSA) is the gold standard for assessing volitional drug use in preclinical studies. We have integrated these approaches to identify novel genes and networks underling cocaine use in mice. Methods Mice from 39 BXD strains acquired cocaine IVSA (0.56 mg/kg/infusion). Mice from 29 BXD strains completed a full dose-response curve (0.032 – 1.8 mg/kg/infusion). Results We identified independent genetic correlations between cocaine IVSA and measures of environmental exploration and cocaine sensitization. We identified genome-wide significant QTL on chromosomes 7 and 11 associated with shifts in the dose-response curve and on chromosome 16 associated with sessions to acquire cocaine IVSA. Using publicly available gene expression data from the nucleus accumbens, midbrain, and prefrontal cortex of drug-naïve mice, we identified Aplp1 and Cyfip2 as positional candidates underlying the behavioral QTL on chromosomes 7 and 11, respectively. A genome-wide significant trans-eQTL linking Fam53b (a GWAS candidate for human cocaine dependence) on chromosome 7 to the cocaine IVSA behavioral QTL on chromosome 11 was identified in the midbrain; Fam53b and Cyfip2 were co-expressed genome-wide significantly in the midbrain. This finding indicates that cocaine IVSA studies using mice can identify genes involved in human cocaine use. Conclusions These data provide novel candidate genes underlying cocaine IVSA in mice, and suggest mechanisms driving human cocaine use. PMID:26581503

  16. Perineural versus intravenous dexamethasone as adjuncts to local anaesthetic brachial plexus block for shoulder surgery.

    PubMed

    Rosenfeld, D M; Ivancic, M G; Hattrup, S J; Renfree, K J; Watkins, A R; Hentz, J G; Gorlin, A W; Spiro, J A; Trentman, T L

    2016-04-01

    This randomised, double-blind, placebo-controlled study compared the effect of perineural with intravenous dexamethasone, both administered concomitantly with interscalene brachial plexus block for shoulder surgery. Patients received 8 mg dexamethasone mixed with ropivacaine in the block injection (n = 42), 8 mg dexamethasone intravenously at the time of the block (n = 37), or intravenous saline (n = 41) at the time of the block. Perineural and intravenous dexamethasone resulted in prolonged mean (SD) duration of block to 16.9 (5.2) h and 18.2 (6.4) h, respectively, compared with 13.8 (3.8) h for saline (p = 0.001). Mean (SD) opioid consumption (morphine equivalents) during the first 24 h after postanaesthesia recovery arrival was 12.2 (9.3) mg in the perineural dexamethasone, 17.1 (15.9) mg in the intravenous dexamethasone and 24.1 (14.3) mg in the saline groups (p = 0.001). Dexamethasone via either route reduced anti-emetic use (p = 0.046). There was no effect on patient satisfaction. These results suggest that both perineural and intravenous dexamethasone are useful adjuncts to ropivacaine interscalene block, with the intravenous route preferred as this avoids the possibility of neural toxicity of dexamethasone.

  17. Efficacy of intravenous nicorandil for fractional flow reserve assessment: study protocol for a crossover randomised trial

    PubMed Central

    Nishi, Takeshi; Kitahara, Hideki; Fujimoto, Yoshihide; Nakayama, Takashi; Sugimoto, Kazumasa; Hanaoka, Hideki; Kobayashi, Yoshio

    2016-01-01

    Introduction Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. Intravenous administration of nicorandil can be applicable for fractional flow reserve (FFR) measurement as a hyperaemic agent and a possible alternative to adenosine. However, the effectiveness of intravenous nicorandil infusion for FFR measurement is largely unclear. Methods and analysis This crossover randomised study is being performed to investigate the efficacy of intravenous administration of nicorandil for FFR measurement. Patients with an intermediate coronary artery stenosis who satisfy the eligibility criteria undergo FFR measurement with a consecutive randomised order of patient-blind infusions of continuous intravenous administration of adenosine and a single bolus intravenous administration of nicorandil. The primary end point of the study is the agreement between the FFR values obtained by the intravenous nicorandil and those obtained by the intravenous adenosine. Recruitment of this trial started in November 2015 and will end in March 2017, or until a total of 50 participants have been recruited. Ethics and dissemination The protocol was approved by the Institutional Review Board at Chiba University Hospital. Study findings will be published in peer-reviewed journals. Trial registration number UMIN000019309; Pre-results. PMID:27872119

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

    PubMed Central

    Pasalioglu, Kadriye Burcu; Kaya, Hatice

    2014-01-01

    Objective: 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. Methods: 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. Conclusion: 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. PMID:25097505

  19. Intravenous Administration of Endothelial Colony-Forming Cells Overexpressing Integrin β1 Augments Angiogenesis in Ischemic Legs.

    PubMed

    Goto, Kazuko; Takemura, Genzou; Takahashi, Tomoyuki; Okada, Hideshi; Kanamori, Hiromitsu; Kawamura, Itta; Watanabe, Takatomo; Morishita, Kentaro; Tsujimoto, Akiko; Miyazaki, Nagisa; Ushikoshi, Hiroaki; Kawasaki, Masanori; Mikami, Atsushi; Kosai, Ken-ichiro; Minatoguchi, Shinya

    2016-02-01

    When injected directly into ischemic tissue in patients with peripheral artery disease, the reparative capacity of endothelial progenitor cells (EPCs) appears to be limited by their poor survival. We, therefore, attempted to improve the survival of transplanted EPCs through intravenous injection and gene modification. We anticipated that overexpression of integrin β1 will enable injected EPCs to home to ischemic tissue, which abundantly express extracellular matrix proteins, the ligands for integrins. In addition, integrin β1 has an independent angiogenesis-stimulating function. Human endothelial colony-forming cells (ECFCs; late-outgrowth EPCs) were transduced using a lentiviral vector encoding integrin β1 (ITGB1) or enhanced green fluorescent protein (GFP). We then locally or systemically injected phosphate-buffered saline or the genetically modified ECFCs (GFP-ECFCs or ITGB1-ECFCs; 1 × 10(5) cells each) into NOD/Shi-scid, IL-2Rγnull mice whose right femoral arteries had been occluded 24 hours earlier. Upregulation of extracellular matrix proteins, including fibronectin, was apparent in the ischemic legs. Four weeks later, blood perfusion of the ischemic limb was significantly augmented only in the ITGB1-ECFC group. Scanning electron microscopy of vascular casts revealed increases in the perfused blood vessels in the ischemic legs of mice in the ITGB1-ECFC group and significant increases in the density of both capillaries and arterioles. Transplanted ECFC-derived vessels accounted for 28% ± 4.2% of the vessels in the ITGB1-ECFC group, with no cell fusion. Intravenous administration of ECFCs engineered to home to ischemic tissue appears to efficiently mediate therapeutic angiogenesis in a mouse model of peripheral artery disease. Significance: The intravenous administration of endothelial colony-forming cells (ECFCs) genetically modified to overexpress integrin β1 effectively stimulated angiogenesis in ischemic mouse hindlimbs. Transplanted ECFCs were

  20. Intravenous Administration of Endothelial Colony-Forming Cells Overexpressing Integrin β1 Augments Angiogenesis in Ischemic Legs

    PubMed Central

    Goto, Kazuko; Takahashi, Tomoyuki; Okada, Hideshi; Kanamori, Hiromitsu; Kawamura, Itta; Watanabe, Takatomo; Morishita, Kentaro; Tsujimoto, Akiko; Miyazaki, Nagisa; Ushikoshi, Hiroaki; Kawasaki, Masanori; Mikami, Atsushi; Kosai, Ken-ichiro; Minatoguchi, Shinya

    2016-01-01

    When injected directly into ischemic tissue in patients with peripheral artery disease, the reparative capacity of endothelial progenitor cells (EPCs) appears to be limited by their poor survival. We, therefore, attempted to improve the survival of transplanted EPCs through intravenous injection and gene modification. We anticipated that overexpression of integrin β1 will enable injected EPCs to home to ischemic tissue, which abundantly express extracellular matrix proteins, the ligands for integrins. In addition, integrin β1 has an independent angiogenesis-stimulating function. Human endothelial colony-forming cells (ECFCs; late-outgrowth EPCs) were transduced using a lentiviral vector encoding integrin β1 (ITGB1) or enhanced green fluorescent protein (GFP). We then locally or systemically injected phosphate-buffered saline or the genetically modified ECFCs (GFP-ECFCs or ITGB1-ECFCs; 1 × 105 cells each) into NOD/Shi-scid, IL-2Rγnull mice whose right femoral arteries had been occluded 24 hours earlier. Upregulation of extracellular matrix proteins, including fibronectin, was apparent in the ischemic legs. Four weeks later, blood perfusion of the ischemic limb was significantly augmented only in the ITGB1-ECFC group. Scanning electron microscopy of vascular casts revealed increases in the perfused blood vessels in the ischemic legs of mice in the ITGB1-ECFC group and significant increases in the density of both capillaries and arterioles. Transplanted ECFC-derived vessels accounted for 28% ± 4.2% of the vessels in the ITGB1-ECFC group, with no cell fusion. Intravenous administration of ECFCs engineered to home to ischemic tissue appears to efficiently mediate therapeutic angiogenesis in a mouse model of peripheral artery disease. Significance The intravenous administration of endothelial colony-forming cells (ECFCs) genetically modified to overexpress integrin β1 effectively stimulated angiogenesis in ischemic mouse hindlimbs. Transplanted ECFCs were observed

  1. [Proven and expected benefits of intravenous lidocaine administered during the perioperative period].

    PubMed

    Giudice, V; Lauwick, S; Kaba, A; Joris, J

    2012-02-01

    Local anesthetics which inhibit sodium channels are used for neural blockade during infiltration and locoregional anesthesia. Furthermore lidocaine given intravenously acts on other cellular systems and produces multiple properties, some of which are beneficial during the perioperative period. Indeed, intravenous lidocaine is analgesic, antihyperalgesic, antiinflammatory, and improves the recovery of bowel function after abdominal surgery. As a consequence, lidocaine has been added to postoperative analgesic strategies. This article reviews clinically relevant properties of intravenous lidocaine. Its future perspectives for the prevention of chronicisation of postoperative pain, facilitation of postoperative fast track programs, and prevention of tumoral recurrence are also discussed.

  2. Pressor response to intravenous tyramine is a marker of cardiac, but not vascular, adrenergic function

    NASA Technical Reports Server (NTRS)

    Meck, Janice V.; Martin, David S.; D'Aunno, Dominick S.; Waters, Wendy W.

    2003-01-01

    Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

  3. Pharmacokinetics of Compounded Intravenous and Oral Gabapentin in Hispaniolan Amazon Parrots ( Amazona ventralis ).

    PubMed

    Baine, Katherine; Jones, Michael P; Cox, Sherry; Martín-Jiménez, Tomás

    2015-09-01

    Neuropathic pain is a manifestation of chronic pain that arises with damage to the somatosensory system. Pharmacologic treatment recommendations for alleviation of neuropathic pain are often multimodal, and the few reports communicating treatment of suspected neuropathic pain in avian patients describe the use of gabapentin as part of the therapeutic regimen. To determine the pharmacokinetics of gabapentin in Hispaniolan Amazon parrots ( Amazona ventralis ), compounded gabapentin suspensions were administered at 30 mg/kg IV to 2 birds, 10 mg/kg PO to 3 birds, and 30 mg/kg PO to 3 birds. Blood samples were collected immediately before and at 9 different time points after drug administration. Plasma samples were analyzed for gabapentin concentration, and pharmacokinetic parameters were calculated with both a nonlinear mixed-effect approach and a noncompartmental analysis. The best compartmental, oral model was used to simulate the concentration-time profiles resulting from different dosing scenarios. Mild sedation was observed in both study birds after intravenous injection. Computer simulation of different dosing scenarios with the mean parameter estimates showed that 15 mg/kg every 8 hours would be a starting point for oral dosing in Hispaniolan Amazon parrots based on effective plasma concentrations reported for human patients; however, additional studies need to be performed to establish a therapeutic dose.

  4. Toxicity of repeated intravenous injection of gene therapeutics for X-CGD in mice.

    PubMed

    Lee, Y M; Choi, W H; Kim, Y B; Ha, C S; Song, C W; Lee, M; Joo, C W; Hong, Y; Ho, S H; Kim, S; Kim, J M; Koh, W S

    2008-05-01

    We made gene therapeutics for X-chronic granulomatous disease (CGD) by transducing murine bone marrow-derived stem cells with MT-gp91 retrovirus and evaluated possible toxicity in mice as a prerequisite for human clinical trials. Male C57BL/6 mice were injected intravenously with gene therapeutics for X-CGD twice at an interval of two weeks at 5 x 10(7) cells/kg and sacrificed 2 weeks after the last administration. Significant changes noted in gene therapeutics for X-CGD-treated animals were an increase in white blood cell counts and a slight decrease in albumin/globulin ratio. The red pulp hyperplasia in the spleen accompanied with an increase in organ weight was considered to result from the accumulation of gene therapeutics for X-CGD, bone marrow-derived stem cells, in the spleen. No anti-gp91 antibody was detected in the sera collected from the animals treated with gene therapeutics for X-CGD. No integration of gp91 DNA from retroviral vector was detected in chromosomal DNA of gonads in animals dosed with the test substance, indicating no potential of genomic integration. In conclusion, the repeated dose of gene therapeutics for X-CGD exerted no toxicity. The splenic red pulp hyperplasia and the increase observed in white blood cell counts and in spleen weights were considered as pharmacological changes induced by the treatment.

  5. [Treatment of immune thrombocytopenic purpura in Pediatrics. Therapeutic efficacy of a regional intravenous immunoglobulin G].

    PubMed

    Buteler, C; Colombo, H; Gabosi, G; Manfredi, M J; Montero, S; Pasquali, M A; Rougier, C; Sisti, A M

    2001-01-01

    Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by accelerated splenic removal of platelets opsonized with autoantibodies. Several different treatments have been tried in acute ITP patients, including intravenous immunoglobulin (IVIG) therapy. The aim of this paper was to assess the therapeutic efficacy, clinical tolerance and viral safety of Inmunoglobulina G Endovenosa-UNC, manufactured by Laboratorio de Hemoderivados, Cordoba National University, in the treatment of acute ITP patients. A prospective longitudinal study was carried out on 8 children, who were admitted to the Hospital de Niños de Córdoba, from July 1998 to June 1999. A dose of 1 g/Kg/day of Inmunoglobulina G Endovenosa-UNC was administered to those children whose platelet values remained < or = 20,000/mm3, 21 days after the first IVIG cycle. The observed results led us to conclude that Inmunoglobulina G Endovenosa-UNC is well tolerated and therapeutically effective in the treatment of acute ITP in children, with platelet values recovery, similar to those obtained with other IVIG. Moreover, it proved to be virally safe since the 8 patients were non reactive for viral markers of hepatitis B, hepatitis C and human immunodeficiency, 12 months after ending the treatment.

  6. Do immune complexes play a role in hemolytic sequelae of intravenous immune globulin?

    PubMed

    Zimring, James C

    2015-07-01

    Intravenous immune globulin (IVIG) was developed initially as an immunoglobulin replacement therapy for primary humoral immunodeficiency, but is now widely used in the treatment of autoinflammatory and autoimmune pathologies. In a small number of patients, hemolytic sequelae have been observed after IVIG administration. The lack of a simple one-to-one correlation between measurable hemagglutinins and hemolysis has led to complicated hypotheses involving coincident necessary variables (e.g., a two-hit hypothesis) and also to the positing of causal factors other than hemagglutinins. One such hypothesis is that immune complexes (ICs) contained within IVIG lead to hemolysis. IVIG-mediated hemolysis was addressed at a recent meeting sponsored by the Food and Drug Administration; the Plasma Protein Therapeutics Association; and the National Heart, Lung, and Blood Institute. The primary literature was reviewed at this meeting followed by detailed discussion. Participants concluded that there is both a theoretical basis by which ICs could contribute to hemolysis after IVIG administration and some published data in support of such a possibility. However, the reported data contain substantial caveats, and the existing evidence does not rise to a level sufficient to either confirm or reject a role for ICs. More detailed and focused human studies will be required to further assess the potential role of ICs in IVIG induced hemolysis. This paper summarizes the relevant literature and expands upon the conclusions of this workshop.

  7. Intravenous injection of a foamy virus vector to correct canine SCID-X1.

    PubMed

    Burtner, Christopher R; Beard, Brian C; Kennedy, Douglas R; Wohlfahrt, Martin E; Adair, Jennifer E; Trobridge, Grant D; Scharenberg, Andrew M; Torgerson, Troy R; Rawlings, David J; Felsburg, Peter J; Kiem, Hans-Peter

    2014-06-05

    Current approaches to hematopoietic stem cell (HSC) gene therapy involve the collection and ex vivo manipulation of HSCs, a process associated with loss of stem cell multipotency and engraftment potential. An alternative approach for correcting blood-related diseases is the direct intravenous administration of viral vectors, so-called in vivo gene therapy. In this study, we evaluated the safety and efficacy of in vivo gene therapy using a foamy virus vector for the correction of canine X-linked severe combined immunodeficiency (SCID-X1). In newborn SCID-X1 dogs, injection of a foamy virus vector expressing the human IL2RG gene resulted in an expansion of lymphocytes expressing the common γ chain and the development of CD3(+) T lymphocytes. CD3(+) cells expressed CD4 and CD8 coreceptors, underwent antigen receptor gene rearrangement, and demonstrated functional maturity in response to T-cell mitogens. Retroviral integration site analysis in 4 animals revealed a polyclonal pattern of integration in all dogs with evidence for dominant clones. These results demonstrate that a foamy virus vector can be administered with therapeutic benefit in the SCID-X1 dog, a clinically relevant preclinical model for in vivo gene therapy.

  8. [Pharmacokinetics of salvianolic acid A after single intravenous administration in Rhesus monkey].

    PubMed

    Song, Jun-ke; Zhang, Wen; Zhang, Wei-ku; Feng, Zhang-ying; Xie, Tao; Du, Guan-Hua

    2015-09-01

    Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.

  9. Does intravenous immune globulin have a role in HIV-infected patients?

    PubMed Central

    Yap, P L

    1994-01-01

    The main immunological abnormality in human immunodeficiency virus (HIV)-infected patients, and particularly those with the acquired immune deficiency syndrome (AIDS), is a deficiency in cellular immunity. However, symptomatic HIV-infected children also have evidence of deficiency of specific antibody synthesis, and intravenous immune globulin (IVIG) preparations in doses of 0.2-0.4 g/kg every 2-4 weeks have been shown to reduce the incidence of respiratory infections. IVIG therapy may also reduce the mortality and incidence of bacterial infections in adults but further studies are required. In addition, high-dose IVIG therapy (1-2 g/kg over 2-5 days) produces increased platelet counts in patients with idiopathic thrombocytopenic purpura (ITP) associated with HIV infection. Finally, IVIG therapy may have a role in HIV-infected patients suffering from severe parvovirus B19 or measles infection, or in patients suffering from autoimmune disorders where high-dose IVIG therapy has been shown to be efficacious. PMID:8033437

  10. Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan.

    PubMed

    Cappelli, Barbara; Chiesa, Robert; Evangelio, Costanza; Biffi, Alessandra; Roccia, Tito; Frugnoli, Ilaria; Biral, Erika; Noè, Anna; Fossati, Marco; Finizio, Valentina; Miniero, Roberto; Napolitano, Sara; Ferrua, Francesca; Soliman, Clara; Ciceri, Fabio; Roncarolo, Maria G; Marktel, Sarah

    2009-11-01

    Hepatic veno-occlusive disease (VOD) is a common complication of haematopoietic stem cell transplantation (HSCT), with reported incidences of 5-40% in children. Recently, defibrotide (DF) has been successfully used as prophylaxis and treatment of VOD. This study reports data on 63 human leucocyte antigen-matched HSCT performed in 57 children affected by beta thalassemia at very high risk for developing VOD (liver fibrosis, iron overload, hepatitis C virus infections, busulphan-based conditioning, methotraexate + ciclosporine). All patients received a busulphan-based conditioning regimen, either orally (four HSCT) or intravenously (59 HSCT). All patients received oral DF (40 mg/kg per day, final dose) as VOD prophylaxis from median day -9 to median day +29. In order to overcome the lack of oral paediatric formulations, a galenic formulation was administered. DF was well tolerated. Only one patient fulfilled Seattle Criteria for VOD diagnosis. This patient had discontinued DF 6 d prior to VOD onset, due to high risk of haemorrhage. We concluded that oral defibrotide prophylaxis and i.v. busulphan safely abated VOD incidence in high-risk patients who had undergone HSCT. A galenic preparation of oral DF also permits this treatment in low-weight patients. Costs of DF prophylaxis are acceptable considering the reduced incidence of VOD.

  11. Peramivir: A Novel Intravenous Neuraminidase Inhibitor for Treatment of Acute Influenza Infections

    PubMed Central

    Alame, Malak M.; Massaad, Elie; Zaraket, Hassan

    2016-01-01

    Peramivir is a novel cyclopentane neuraminidase inhibitor of influenza virus. It was approved by the Food and Drug Administration in December 2014 for treatment of acute uncomplicated influenza in patients 18 years and older. For several months prior to approval, the drug was made clinically available under Emergency Use authorization during the 2009 H1N1 influenza pandemic. Peramivir is highly effective against human influenza A and B isolates as well as emerging influenza virus strains with pandemic potential. Clinical trials demonstrated that the drug is well-tolerated in adult and pediatric populations. Adverse events are generally mild to moderate and similar in frequency to patients receiving placebo. Common side effects include gastrointestinal disorders and decreased neutrophil counts but are self-limiting. Peramivir is administered as a single-dose via the intravenous route providing a valuable therapeutic alternative for critically ill patients or those unable to tolerate other administration routes. Successful clinical trials and post-marketing data in pediatric populations in Japan support the safety and efficacy of peramivir in this population where administration of other antivirals might not be feasible. PMID:27065996

  12. Comparative Evaluation of Nephrotoxicity and Management by Macrophages of Intravenous Pharmaceutical Iron Formulations

    PubMed Central

    Connor, James R.; Zhang, Xuesheng; Nixon, Anne M.; Webb, Becky; Perno, Joseph R.

    2015-01-01

    Background There is a significant clinical need for effective treatment of iron deficiency. A number of compounds that can be administered intravenously have been developed. This study examines how the compounds are handled by macrophages and their relative potential to provoke oxidative stress. Methods Human kidney (HK-2) cells, rat peritoneal macrophages and renal cortical homogenates were exposed to pharmaceutical iron preparations. Analyses were performed for indices of oxidative stress and cell integrity. In addition, in macrophages, iron uptake and release and cytokine secretion was monitored. Results HK-2 cell viability was decreased by iron isomaltoside and ferumoxytol and all compounds induced lipid peroxidation. In the renal cortical homogenates, lipid peroxidation occurred at lowest concentrations with ferric carboxymaltose, iron dextran, iron sucrose and sodium ferric gluconate. In the macrophages, iron sucrose caused loss of cell viability. Iron uptake was highest for ferumoxytol and iron isomaltoside and lowest for iron sucrose and sodium ferric gluconate. Iron was released as secretion of ferritin or as ferrous iron via ferroportin. The latter was blocked by hepcidin. Exposure to ferric carboxymaltose and iron dextran resulted in release of tumor necrosis factor α. Conclusions Exposure to iron compounds increased cell stress but was tissue and dose dependent. There was a clear difference in the handling of iron from the different compounds by macrophages that suggests in vivo responses may differ. PMID:25973894

  13. Brain targeting effect of camptothecin-loaded solid lipid nanoparticles in rat after intravenous administration.

    PubMed

    Martins, Susana M; Sarmento, Bruno; Nunes, Cláudia; Lúcio, Marlene; Reis, Salette; Ferreira, Domingos C

    2013-11-01

    This study intended to investigate the ability of solid lipid nanoparticles (SLN) to deliver camptothecin into the brain parenchyma after crossing the blood-brain barrier. For that purpose, camptothecin-loaded SLN with mean size below 200 nm, low polydispersity index (<0.25), negative surface charge (-20 mV), and high camptothecin association efficiency (>94%) were produced. Synchrotron small and wide angle X-ray scattering (SAXS/WAXS) analysis indicates that SLN maintain their physical stability in contact with DMPC membrane, whereas SLN change the lamellar structure of DMPC into a cubic phase, which is associated with efficient release of the incorporated drugs. Cytotoxicity studies against glioma and macrophage human cell lines revealed that camptothecin-loaded SLN induced cell death with the lowest maximal inhibitory concentration (IC50) values, revealing higher antitumour activity of camptothecin-loaded SLN against gliomas. Furthermore, in vivo biodistribution studies of intravenous camptothecin-loaded SLN performed in rats proved the positive role of SLN on the brain targeting since significant higher brain accumulation of camptothecin was observed, compared to non-encapsulated drug. Pharmacokinetic studies further demonstrated lower deposition of camptothecin in peripheral organs, when encapsulated into SLN, with consequent decrease in potential side toxicological effects. These results confirmed the potential of camptothecin-loaded SLN for antitumour brain treatments.

  14. Second infection with a different hepatitis C virus genotype in a intravenous drug user during interferon therapy.

    PubMed

    Asselah, T; Vidaud, D; Doloy, A; Boyer, N; Martinot, M; Vidaud, M; Valla, D; Marcellin, P

    2003-06-01

    The prevalence of antibodies against hepatitis C virus (anti-HCV) among intravenous drug users (IVDU) has consistently been very high. Cross challenge studies in chimpanzees provide evidence that reinfection with different HCV strains may occur. In humans, reinfection with different HCV strains has been reported in multitransfused haemophiliacs and recently in IVDU but no case has been reported while on interferon (IFN) therapy. We report on a 22 year old woman who was treated with IFN alpha for HCV genotype 3a chronic infection. At six months, HCV RNA was undetectable by reverse transcription-polymerase chain reaction. In October 1997, while still on IFN, she developed an acute hepatitis after an intravenous drug injection and HCV genotype 1a infection was identified using genotyping and sequencing methods. IFN therapy was continued until August 1998, and in January 1999 HCV-RNA was not detectable. Our case indicates that the previous HCV infection might have prevented development of chronicity. An alternative explanation is that IFN, while not preventing acute hepatitis C, may prevent chronicity. The risk of multiple infection in IVDU underlines the need for preventive strategies.

  15. AT2R Gene Delivered by Condensed Polylysine Complexes Attenuates Lewis Lung Carcinoma after Intravenous Injection or Intratracheal Spray.

    PubMed

    Alhakamy, Nabil A; Ishiguro, Susumu; Uppalapati, Deepthi; Berkland, Cory J; Tamura, Masaaki

    2016-01-01

    Transfection efficiency and toxicity concerns remain a challenge for gene therapy. Cell-penetrating peptides (CPP) have been broadly investigated to improve the transfection of genetic material (e.g., pDNA and siRNA). Here, a synthetic CPP (polylysine, K9 peptide) was complexed with angiotensin II type 2 receptor (AT2R) plasmid DNA (pAT2R) and complexes were condensed using calcium chloride. The resulting complexes were small (∼150 nm) and showed high levels of gene expression in vitro and in vivo. This simple nonviral formulation approach showed negligible cytotoxicity in four different human cell lines (cervix, breast, kidney, and lung cell lines) and one mouse cell line (a lung cancer cell line). In addition, this K9-pDNA-Ca(2+) complex demonstrated cancer-targeted gene delivery when administered via intravenous injection or intratracheal spray. The transfection efficiency was evaluated in Lewis lung carcinoma (LLC) cell lines cultured in vitro and in orthotopic cancer grafts in syngeneic mice. Immunohistochemical analysis confirmed that the complex effectively delivered pAT2R to the cancer cells, where it was expressed mainly in cancer cells along with bronchial epithelial cells. A single administration of these complexes markedly attenuated lung cancer growth, offering preclinical proof-of-concept for a novel nonviral gene delivery method exhibiting effective lung tumor gene therapy via either intravenous or intratracheal administration.

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

    PubMed Central

    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

  17. Portable Intravenous Fluid Production Device For Ground Use Project

    NASA Technical Reports Server (NTRS)

    Oliva-Buisson, Yvette J.

    2014-01-01

    Several medical conditions require the administration of intravenous (IV) fluids,but limitations of mass, volume, shelf-life, transportation, and local resources can restrict the availability of these important fluids. Such limitations are expected in long-duration space exploration missions and in remote or austere places on Earth. This design uses regular drinking water that is pumped through two filters to produce, in minutes, sterile, ultrapure water that meets the stringent quality standards of the United States Pharmacopeia for Water for Injection (Total Bacteria, Conductivity, Endo - toxins, Total Organic Carbon). The device weighs 2.2 lb (1 kg) and is 10 in. long, 5 in. wide, and 3 in. high (˜25, 13, and 7.5 cm, respectively) in its storage configuration. This handheld device produces one liter of medical-grade water in 21 minutes. Total production capacity for this innovation is expected to be in the hundreds of liters. The device contains one battery powered electric mini-pump. Alternatively, a manually powered pump can be attached and used. Drinking water enters the device from a source water bag, flows through two filters, and final sterile production water exits into a sealed, medical-grade collection bag. The collection bag contains pre-placed crystalline salts to mix with product water to form isotonic intravenous medical solutions. Alternatively, a hypertonic salt solution can be injected into a filled bag. The filled collection bag is detached from the device and is ready for use or storage. This device currently contains one collection bag, but a manifold of several pre-attached bags or replacement of single collection bags under sterile needle technique is possible for the production of multiple liters. The entire system will be flushed, sealed, and radiation-sterilized. Operation of the device is easy and requires minimal training. Drinking water is placed into the collection bag. Inline stopcock flow valves at the source and collection bags

  18. Intravenous iron administration and hypophosphatemia in clinical practice.

    PubMed

    Hardy, S; Vandemergel, X

    2015-01-01

    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.

  19. Multiple Intravenous Infusions Phase 2a: Ontario Survey

    PubMed Central

    Fan, Mark; Koczmara, Christine; Masino, Caterina; Cassano-Piché, Andrea; Trbovich, Patricia; Easty, Anthony

    2014-01-01

    Background Research conducted in earlier phases of this study prospectively identified a number of concerns related to the safe administration of multiple intravenous (IV) infusions in Ontario hospitals. Objective To investigate the potential prevalence of practices or policies that may contribute to the patient safety risks identified in Phase 1b of this study. Data Sources and Review Methods Sixty-four survey responses were analyzed from clinical units where multiple IV infusions may occur (e.g., adult intensive care units). Survey questions were organized according to the topics identified in Phase 1b as potential contributors to patient harm (e.g., labelling practices, patient transfer practices, secondary infusion policies). Results Survey results indicated suboptimal practices and policies in some clinical units, and variability in a number of infusion practices. Key areas of concern included the following: use of primary IV tubing without back check valves when administering secondary infusions administration of secondary infusions with/as high-alert continuous IV medications potential confusion about how IV tubing should be labelled to reflect replacement date and time interruptions to IV therapy due to IV pump and/or tubing changes when patients are transferred between clinical units coadministration of continuous or intermittent infusions on central venous pressure monitoring ports variability in respondents’ awareness of the infusion pump's bolus capabilities Limitations Due to the limited sample size, survey responses may not be representative of infusion practices across Ontario. Answers to some questions indicated that the intent of the questions might have been misunderstood. Due to a design error, 1 question about bolus administration methods was not shown to as many respondents as appropriate. Conclusions The Ontario survey revealed variability in IV infusion practice across the province and potential opportunities to improve safety. PMID

  20. Multiorgan crystal deposition following intravenous oxalate infusion in rat

    SciTech Connect

    Blumenfrucht, M.J.; Cheeks, C.; Wedeen, R.P.

    1986-06-01

    Deposition of calcium oxalate is responsible for the pathologic manifestations of oxalosis and may contribute to multiorgan dysfunction in uremia and to the progression of renal damage after renal failure is established. We have developed a rat model of oxalosis using a single intravenous injection of sodium oxalate, 0.3 mmol./kg. body weight, in rats. Polarized light microscopy and section freeze-dry autoradiography were used to identify /sup 14/C-oxalate within the renal parenchyma and in extrarenal organs. /sup 14/C-oxalate crystals under three mu in length were identified within one min. of injection in proximal tubule lumens. Section freeze-dry autoradiography showed occasional minute crystals within glomeruli, heart, lung and liver at one hr. In contrast to concentrative cellular uptake demonstrated in rat renal cortical slices in vitro, intracellular accumulation of /sup 14/C-oxalate could not be detected in vivo. Within the first 24 hr., renal oxalate retention reached a maximum of 25 +/- 4 per cent of the injected dose/gm. kidney compared to a maximum of only 7 +/- 3 per cent/gm. kidney after intraperitoneal administration. Although less than one per cent dose/gm. kidney remained after one week, crystal fragments were scattered throughout the cortex and medulla, often surrounded by foci of interstitial nephritis. The retention of crystals in kidney and other body organs following i.v. oxalate provides a model of oxalosis which stimulates pathophysiologic events in a variety of clinical situations characterized by transiently or persistently elevated serum oxalate.

  1. Multiple Intravenous Infusions Phase 2b: Laboratory Study

    PubMed Central

    Pinkney, Sonia; Fan, Mark; Chan, Katherine; Koczmara, Christine; Colvin, Christopher; Sasangohar, Farzan; Masino, Caterina; Easty, Anthony; Trbovich, Patricia

    2014-01-01

    Background Administering multiple intravenous (IV) infusions to a single patient via infusion pump occurs routinely in health care, but there has been little empirical research examining the risks associated with this practice or ways to mitigate those risks. Objectives To identify the risks associated with multiple IV infusions and assess the impact of interventions on nurses’ ability to safely administer them. Data Sources and Review Methods Forty nurses completed infusion-related tasks in a simulated adult intensive care unit, with and without interventions (i.e., repeated-measures design). Results Errors were observed in completing common tasks associated with the administration of multiple IV infusions, including the following (all values from baseline, which was current practice): setting up and programming multiple primary continuous IV infusions (e.g., 11.7% programming errors) identifying IV infusions (e.g., 7.7% line-tracing errors) managing dead volume (e.g., 96.0% flush rate errors following IV syringe dose administration) setting up a secondary intermittent IV infusion (e.g., 11.3% secondary clamp errors) administering an IV pump bolus (e.g., 11.5% programming errors) Of 10 interventions tested, 6 (1 practice, 3 technology, and 2 educational) significantly decreased or even eliminated errors compared to baseline. Limitations The simulation of an adult intensive care unit at 1 hospital limited the ability to generalize results. The study results were representative of nurses who received training in the interventions but had little experience using them. The longitudinal effects of the interventions were not studied. Conclusions Administering and managing multiple IV infusions is a complex and risk-prone activity. However, when a patient requires multiple IV infusions, targeted interventions can reduce identified risks. A combination of standardized practice, technology improvements, and targeted education is required. PMID:26316919

  2. Stroke Code Improves Intravenous Thrombolysis Administration in Acute Ischemic Stroke

    PubMed Central

    Chen, Chih-Hao; Tang, Sung-Chun; Tsai, Li-Kai; Hsieh, Ming-Ju; Yeh, Shin-Joe; Huang, Kuang-Yu; Jeng, Jiann-Shing

    2014-01-01

    Background and Purpose 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. Methods 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. Results 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. Conclusion The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time. PMID:25111200

  3. Safety of oral and intravenous mycophenolate mofetil in healthy cats.

    PubMed

    Slovak, Jennifer E; Villarino, Nicolas F

    2017-02-01

    Objectives The aim of this study was to evaluate the safety and clinical effects of intravenous (IV) and oral mycophenolate mofetil (MMF) in healthy cats. Methods A total of 24 healthy adult cats weighing >3.5 kg were either administered IV MMF (over a 2 h infusion) or oral MMF. The dosages used were as follows: 5 mg/kg IV once (n = 2), 10 mg/kg q12h IV for 1 day (n = 1), 20 mg/kg q12h IV for 1 day (n = 6) and 10 mg/kg q12h IV for 3 days (n = 5). Blood was collected from each cat at intervals of up to 12 h from the last dose for analysis purposes. Oral MMF was given at 10 mg/kg q12h for 7 days (n = 3), 15 mg/kg q12h for 7 days (n = 3) and 15 mg/kg q8h for 7 days (n = 4). Results Side effects to MMF were minimal. There was no anorexia or vomiting noted in any of the cats during or after IV medication administration. Only 4/14 cats had diarrhea from 12-48 h after IV administration. There was hyporexia in 1/10 cats given oral MMF and no vomiting noted. In 5/10 cats given oral MMF, there was diarrhea between days 2 and 7 of the study. Conclusions and relevance Cats tolerate MMF at an IV dose of 10 mg/kg q12h for 3 days and an oral dose ⩽15 mg/kg q12h for up to 7 days. There seems to be a dose-dependent incidence of gastrointestinal side effects. MMF may be a useful alternative immunosuppressant to be considered for use in some cats.

  4. Phase I study of intravenous iododeoxyuridine as a clinical radiosensitizer

    SciTech Connect

    Kinsella, T.J.; Russo, A.; Mitchell, J.B.; Collins, J.M.; Rowland, J.; Wright, D.; Glatstein, E.

    1985-11-01

    Twenty-four patients with locally advanced (19 patients) or metastatic (5 patients) tumors were treated in a Phase I study combining constant intravenous infusions of iododeoxyuridine (IUdR) and hyperfractionated radiation therapy. IUdR was given as a constant infusion for 12 hours/day for two separate 14-day infusion periods in most patients. The dose of IUdR was escalated from 250 to 1200 mg/m2/12-hour infusion in this study. The initial tumor volume was treated to 45 Gy/1.5 Gy BID/3 weeks followed by a cone-down boost to 20-25 Gy/1.25 Gy BID/2 weeks after a planned 2-week break. THe IUdR infusion preceded the initial and cone-down irradiation by 1 week. Local acute toxicity (within the radiation volume) was uncommon and few patients required an alteration of the planned treatment schedule. Two patients developed late local toxicity with one patient showing clinical signs of radiation hepatitis and another patient developing a large bowel obstruction that required surgical bypass. Dose-limiting systemic toxicity was confined to the bone marrow with moderate to severe thrombocytopenia developing on Day 10-14 of infusions at 1200 mg/m2/12 hours. Mild stomatitis and partial alopecia occurred in some patients at this dose level. No systemic skin toxicity was seen. Pharmacology studies revealed steady-state arterial plasma levels of IUdR of 1 to 8 X 10(-6) M over the dose range used. In vivo IUdR incorporation into tumors was studied in three patients with high-grade sarcomas using an anti-IUdR monoclonal antibody and immunohistochemistry and demonstrated incorporation in up to 50-70% of tumor cells. The preliminary treatment results, particularly in patients with unresectable sarcomas, are encouraging.

  5. Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer

    SciTech Connect

    Kinsella, T.J.; Mitchell, J.B.; Russo, A.; Aiken, M.; Morstyn, G.; Hsu, S.M.; Rowland, J.; Glatstein, E.

    1984-10-01

    Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 x 10(-7) mol/L and 1 x 10(-6) mol/L during infusion of 650 and 1000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). The authors conclude that local and systemic toxicity of continuous infusion of BUdR at 1000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.

  6. Successful management of intractable cryptosporidial diarrhea with intravenous octreotide, a somatostatin analogue.

    PubMed

    Kreinik, G; Burstein, O; Landor, M; Bernstein, L; Weiss, L M; Wittner, M

    1991-06-01

    A 38-year-old man with AIDS and intractable large-volume diarrhea due to a cryptosporidial infection was successfully treated with intravenous octreotide, a somatostatin analogue. The volume of diarrhea, 10-12 liters with 8-13 movements per day, was reduced to three to four semi-formed to formed stools per day when the patient was treated with 400 micrograms intravenous octreotide daily. The patient's intravenous hyperalimentation was discontinued and he returned to oral feeding. He quickly regained his normal weight and has now resumed his normal activities. For those patients who cannot tolerate subcutaneous administration, intravenous octreotide therapy may not only be life-saving but may also markedly increase the quality of life. Roxithromycin, a macrolide antibiotic, was also administered to this patient with cryptosporidiosis but efficacy was not demonstrated.

  7. Nanocarriers and the delivered drug: effect interference due to intravenous administration.

    PubMed

    Vlasova, Maria A; Rytkönen, Jussi; Riikonen, Joakim; Tarasova, Olga S; Mönkäre, Juha; Kovalainen, Miia; Närvänen, Ale; Salonen, Jarno; Herzig, Karl-Heinz; Lehto, Vesa-Pekka; Järvinen, Kristiina

    2014-10-15

    Intravenously administered nanocarriers are widely studied to improve the delivery of various therapeutic agents. However, recent in vivo studies have demonstrated that intravenously administered nanocarriers that do not contain any drug may affect cardiovascular function. Here we provide an example where the drug and the nanocarrier both affect the same cardiovascular parameters following intravenous administration. The peptide ghrelin antagonist (GhA) increases arterial pressure, while thermally hydrocarbonized porous silicon nanoparticles (THCPSi) transiently decrease it, as assessed with radiotelemetry in conscious rats. As a result, intravenous administration of GhA-loaded THCPSi nanoparticles partially antagonized GhA activity: arterial pressure was not increased. When the cardiovascular effects of GhA were blocked with atenolol pretreatment, GhA-loaded nanoparticles reduced arterial pressure to similar extent as drug-free nanoparticles. These data indicate that the biological activity of a drug delivered within a nanocarrier may be obscured by the biological responses induced by the nanocarrier itself.

  8. Severe and prolonged hypophosphatemia after intravenous iron administration in a malnourished patient.

    PubMed

    Fierz, Y C; Kenmeni, R; Gonthier, A; Lier, F; Pralong, F; Coti Bertrand, P

    2014-04-01

    Malnutrition may result in a phosphate-deficient state owing to a chronically insufficient phosphate intake. Concomitant iron deficiency is common and often supplemented by the intravenous route. It is not widely recognized that some parenteral iron formulations can induce hypophosphatemia. Herein we report a case of a severe and symptomatic hypophosphatemia (0.18 mM, normal range 0.8-1.4 mM) associated with an inappropriately reduced tubular reabsorption of phosphate (33%, norm >95%) in a malnourished patient with anorexia/bulimia who received 2 × 500 mg iron carboxymaltose (FCM) intravenously. Despite intravenous and oral phosphate supplements, it required 2 months to achieve a normal serum phosphate level. Our case demonstrates that in a chronically malnourished and phosphate-deficient state intravenous FCM could potentially be dangerous. If this form of iron application cannot be avoided, phosphate supplementation before and after iron infusion as well as close monitoring of phosphate levels are needed.

  9. Soluble CD4 antigen reactivity in intravenous immunoglobulin preparations: is it specific?

    PubMed Central

    Perosa, F; Rizzi, R; Pulpito, V; Dammacco, F

    1995-01-01

    Soluble CD4 antigen (sCD4) was measured in seven commercially available intravenous immunoglobulin preparations (IVIg) by means of a double determinant immunoassay (DDIA), whereby two MoAbs recognizing two distinct and spatially distant epitopes on CD4 were used to capture and detect the antigen, respectively. Preincubation of six out of seven IVIg, which were found to be apparently positive for sCD4, with mouse- and bovine-derived serum or purified immunoglobulins completely neutralized DDIA reactivity for sCD4. The inhibition was specific since it was not or only partially observed when IVIg were mixed with whole serum or purified IgG from rabbit. Extensive absorption of six IVIg on insolubilized mouse IgG (mIgG) resulted in a complete loss of reactivity. Eluted human anti-mouse antibodies (HAMA) from any of the IVIg displayed a dose-dependent binding in a DDIA, though its extent varied from one preparation to another. Western blot analysis showed that HAMA from all IVIg contained no component with a molecular weight identical with or close to that of recombinant CD4. Purified mIgG markedly influenced the sCD4 reactivity of two IVIg (Sandoglobulin and Globuman I.V.) when sCD4 was measured with a purchased 'CD4-specific Test Kit', thus suggesting that HAMA can exceed the absorbing capacity of the sample diluent. Taken as a whole, these data indicate that sCD4-based DDIA signal is mostly, if not completely, generated by the presence of human immunoglobulin with anti-mouse immunoglobulin reactivity, thus casting doubts on the actual occurrence of sCD4 in IVIg. Images Fig. 4 PMID:7813106

  10. Alterations in the striatal dopamine system during intravenous methamphetamine exposure: effects of contingent and noncontingent administration.

    PubMed

    Laćan, Goran; Hadamitzky, Martin; Kuczenski, Ronald; Melega, William P

    2013-08-01

    The continuing spread of methamphetamine (METH) abuse has stimulated research aimed at understanding consequences of its prolonged exposure. Alterations in nigrostriatal dopamine (DA) system parameters have been characterized in experimental studies after discontinuation of long-term METH but fewer studies have included similar assessments during METH exposure. Here, we report METH plasma pharmacokinetics and striatal DA system alterations in rat after noncontingent and contingent METH administration for 7.5 weeks. Escalating METH exposure was delivered by dynamic infusion (DI) that incorporated a "humanized" plasma METH half life or by intravenous self-administration (IVSA) that included binge intakes. Kinetic modeling of DI and IVSA for 24 h periods during the final week of METH exposure showed that plasma METH levels remained between 0.7 and 1.5 µM. Animals were sacrificed during their last METH administration for autoradiography assessment using [³H]ligands and D2 agonist-induced [³⁵S]GTPγS binding. DA transporter binding was decreased (DI, 34%; IVSA, 15%) while vesicular monoamine transporter binding and substantia nigra DA cell numbers were unchanged. Decreases were measured for D2 receptor (DI and IVSA, 15-20%) and [³⁵S]GTPγS binding (DI, 35%; IVSA, 18%). These similar patterns of DI and IVSA associated decreases in striatal DA markers reflect consequences of cumulative METH exposure and not the drug delivery method. For METH IVSA, individual differences were observed, yet each animal's total intake was similar within and across three 24-h binges. IVSA rodent models may be useful for identifying molecular mechanisms that are associated with METH binges in humans.

  11. Pharmacokinetics of intravenous ibuprofen: implications of time of infusion in the treatment of pain and fever.

    PubMed

    Smith, Howard S; Voss, Bryan

    2012-02-12

    Intravenous NSAIDs are playing an increasingly large role in analgesia, anti-inflammation and antipyresis in the hospitalized setting. For many years, ketorolac was the only intravenous NSAID available in the US, but in 2009 intravenous ibuprofen was approved by the US FDA for the treatment of pain and fever in adults. In developing intravenous ibuprofen, a range of times of infusion and dosing levels have been utilized and compared with the oral route of administration. The earliest studies utilized a 60-minute infusion, and later a 30-minute infusion was used for the pivotal/registration studies demonstrating efficacy and safety. Another recent trial in healthy volunteers demonstrated a safe and tolerable rapid infusion (5-7 minute) of intravenous ibuprofen. The pharmacokinetic data from all of the clinical trials on 400 and 800 mg doses of intravenous ibuprofen were compiled, and pharmacokinetic modelling was utilized to simulate any data not acquired in the clinical studies. The pharmacokinetic profile of the following doses was modelled: 30-minute infusion of 800 mg intravenous ibuprofen, 5- to 7-minute infusion of 400 mg intravenous ibuprofen and 400 mg ibuprofen oral tablet. These pharmacokinetic analyses revealed that, in general, maximum plasma concentration (C(max)) decreases considerably as the length of the infusion increases and that an oral dose is not able to achieve the C(max) level of any intravenous dose. For the rapid infusion, C(max) was twice that of the oral dose and, as expected, time to C(max) (t(max)) was much more rapid than with the oral dose. However, the oral dose still maintained virtually 100% oral bioavailability. The efficacy of intravenous ibuprofen in terms of pain and fever has also been studied and this review found the drug to be efficacious for both indications. Future areas of study should include assessment of the analgesic and antipyretic efficacy of a rapid (5- to 10-minute) infusion and further assessment of pre

  12. Comparison of Iontophoretic Lidocaine to EMLA Cream for Pain Reduction Prior to Intravenous Fannulation in Adults

    DTIC Science & Technology

    2000-10-01

    i COMPARISON OF IONTOPHORETIC LIDOCAINE TO EMLA CREAM FOR PAIN REDUCTIONPRIOR TO INTRAVENOUS CANNULATION IN ADULTS Kenneth Lee Spence LT, NC, USN...COMPARISON OF IONTOPHORETIC LIDOCAINE TO EMLA CREAM FOR PAIN REDUCTION PRIOR TO INTRAVENOUS CANNULATION IN ADULTS 5a. CONTRACT NUMBER 5b. GRANT...most operative anesthesia, can be a source of pain and anxiety. Lidocaine , a local anesthetic, is frequently injected intradermally to decrease pain

  13. Affinity of Mucormycosis for Basal Ganglia in Intravenous Drug Users: Case Illustration and Review of Literature.

    PubMed

    Hazama, Ali; Galgano, Michael; Fullmer, Joseph; Hall, Walter; Chin, Lawrence

    2017-02-01

    Central nervous system mucormycosis is an aggressive fungal infection often ending in fatality. The usual circumstance is an immunocompromised individual presenting with rapidly progressive rhinocerebral involvement. An extremely rare variant of central nervous system mucormycosis isolated to the basal ganglia in an immunocompetent intravenous drug user is detailed in this manuscript. The patient was aggressively treated with aspiration of the fungal abscess and long-term intravenous antifungal agents.

  14. Efficacy and safety of intravenous iron sucrose in treating adults with iron deficiency anemia

    PubMed Central

    Cançado, Rodolfo Delfini; de Figueiredo, Pedro Otavio Novis; Olivato, Maria Cristina Albe; Chiattone, Carlos Sérgio

    2011-01-01

    Background Iron deficiency is the most common disorder in the world, affecting approximately 25% of the world`s population and the most common cause of anemia. Objective To evaluate the efficacy and safety of intravenous iron sucrose (IS) in the treatment of adults with iron deficiency anemia Methods Eighty-six adult patients with iron deficiency anemia, who had intolerance or showed no effect with oral iron therapy, received a weekly dose of 200 mg of intravenous iron sucrose until the hemoglobin level was corrected or until receiving the total dose of intravenous iron calculated for each patient Results The mean hemoglobin and serum ferritin levels were 8.54 g/dL and 7.63 ng/mL (pre-treatment) and 12.1 g/dL and 99.0 ng/mL (post-treatment) (p-value < 0.0001), respectively. The average increases in hemoglobin levels were 3.29 g/dL for women and 4.58 g/dL for men; 94% of male and 84% of female patients responded (hemoglobin increased by at least 2 g/dL) to intravenous iron therapy. Correction of anemia was obtained in 47 of 69 (68.1%) female patients and in 12 of 17 male (70.6%) patients. A total of 515 intravenous infusions of iron sucrose were administered and iron sucrose was generally well tolerated with no moderate or serious adverse drug reactions recorded by the investigators. Conclusions Our data confirm that the use of intravenous iron sucrose is a safe and effective option in the treatment of adult patients with iron deficiency anemia who lack satisfactory response to oral iron therapy. Intravenous iron sucrose is well tolerated and with a clinically manageable safety profile when using appropriate dosing and monitoring. The availability of intravenous iron sucrose would potentially improve compliance and thereby reduce morbidities from iron deficiency. PMID:23049360

  15. Use of intravenous propranolol for control of a large cervicofacial hemangioma in a critically ill neonate.

    PubMed

    Fernando, Shanik J; Leitenberger, Sabra; Majerus, Matt; Krol, Alfons; MacArthur, Carol J

    2016-05-01

    Cervicofacial segmental infantile hemangiomas (IH) may result in airway obstruction requiring use of propranolol to induce hemangioma regression and reestablish the airway. We present the first case using intravenous (IV) propranolol for control of airway obstruction and rapid expansion of cervicofacial IH in the setting of necrotizing enterocolitis (NEC) impaired gastrointestinal function. Intravenous dosing of propranolol was tolerated well in a critically ill neonate with multisystem complications of prematurity.

  16. A Pediatric Diabetic Ketoacidosis Management Protocol Incorporating a Two-Bag Intravenous Fluid System Decreases Duration of Intravenous Insulin Therapy

    PubMed Central

    Marsh, Kourtney; Norman, Susan; Brock, Michael Alan; Peng, Monica; Shenk, Jennifer; Chen, Jerome Gene

    2016-01-01

    OBJECTIVES: Diabetic ketoacidosis (DKA) is a leading cause of morbidity and mortality in children with type 1 diabetes. We implemented a standardized DKA management protocol by using a 2-bag intravenous (IV) fluid system. The purpose of the study was to examine if the protocol improved clinical outcomes and process efficiency. METHODS: This was a retrospective study of patients who did and did not undergo the protocol. Patients were included if they were 18 years of age or younger, were diagnosed with DKA, admitted to an intensive care unit or stepdown unit, and received continuous IV insulin. RESULTS: Of 119 encounters evaluated, 46 (38.7%) received treatment with the protocol and 73 (61.3%) did not. The median time to normalization of ketoacidosis was 9 hours (IQR 5–12) and 9 hours (IQR 6.5–13) for protocol and non-protocol groups, respectively (p = 0.14). The median duration of IV insulin therapy was 16.9 hours (IQR 13.7–21.5) vs. 21 hours (IQR 15.3–26) for protocol and non-protocol groups (p = 0.03). The median number of adjustments to insulin drip rate was 0 (IQR 0–1) and 2 (IQR 0–3) for protocol and non-protocol groups (p = 0.0001). There was no difference in the incidence of hypokalemia, hypoglycemia, or cerebral edema. CONCLUSIONS: The protocol did not change time to normalization of ketoacidosis but did decrease the duration of insulin therapy, number of adjustments to insulin drip rate, and number of wasted IV fluid bags without increasing the incidence of adverse events. PMID:28018153

  17. A Pediatric Diabetic Ketoacidosis Management Protocol Incorporating a Two-Bag Intravenous Fluid System Decreases Duration of Intravenous Insulin Therapy.

    PubMed

    Veverka, Megan; Marsh, Kourtney; Norman, Susan; Brock, Michael Alan; Peng, Monica; Shenk, Jennifer; Chen, Jerome Gene

    2016-01-01

    OBJECTIVES: Diabetic ketoacidosis (DKA) is a leading cause of morbidity and mortality in children with type 1 diabetes. We implemented a standardized DKA management protocol by using a 2-bag intravenous (IV) fluid system. The purpose of the study was to examine if the protocol improved clinical outcomes and process efficiency. METHODS: This was a retrospective study of patients who did and did not undergo the protocol. Patients were included if they were 18 years of age or younger, were diagnosed with DKA, admitted to an intensive care unit or stepdown unit, and received continuous IV insulin. RESULTS: Of 119 encounters evaluated, 46 (38.7%) received treatment with the protocol and 73 (61.3%) did not. The median time to normalization of ketoacidosis was 9 hours (IQR 5-12) and 9 hours (IQR 6.5-13) for protocol and non-protocol groups, respectively (p = 0.14). The median duration of IV insulin therapy was 16.9 hours (IQR 13.7-21.5) vs. 21 hours (IQR 15.3-26) for protocol and non-protocol groups (p = 0.03). The median number of adjustments to insulin drip rate was 0 (IQR 0-1) and 2 (IQR 0-3) for protocol and non-protocol groups (p = 0.0001). There was no difference in the incidence of hypokalemia, hypoglycemia, or cerebral edema. CONCLUSIONS: The protocol did not change time to normalization of ketoacidosis but did decrease the duration of insulin therapy, number of adjustments to insulin drip rate, and number of wasted IV fluid bags without increasing the incidence of adverse events.

  18. Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study.

    PubMed

    Steele, Megan L; Axtner, Jan; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann

    2014-01-01

    Background. Traditional mistletoe therapy in cancer patients involves subcutaneous applications of Viscum album L. preparations, with doses slowly increasing based on patient responses. Intravenous infusion of high doses may improve therapeutic outcomes and is becoming more common. Little is known about the safety of this "off-label" application of mistletoe. Methods. An observational study was performed within the Network Oncology. Treatment with intravenous mistletoe applications is described. The frequency of adverse drug reactions (ADRs) to intravenous mistletoe applications was calculated and compared to ADR data from a study on subcutaneous applications. Results. Of 475 cancer patients who received intravenous infusions of Helixor, Abnoba viscum, or Iscador mistletoe preparations, 22 patients (4.6%) reported 32 ADRs of mild (59.4%) or moderate severity (40.6%). No serious ADRs occurred. ADRs were more frequently reported to i.v. mistletoe administered alone (4.3%), versus prior to chemotherapy (1.6%). ADR frequency differed with respect to preparation type, with Iscador preparations showing a higher relative frequency, compared to Abnoba viscum and Helixor. Overall, patients were almost two times less likely to experience an ADR to intravenous compared to subcutaneous application of mistletoe. Conclusion. Intravenous mistletoe therapy was found to be safe and prospective studies for efficacy are recommended.

  19. Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.

    PubMed

    van der Westhuizen, J; Kuo, P Y; Reed, P W; Holder, K

    2011-03-01

    Gastric absorption of oral paracetamol (acetaminophen) may be unreliable perioperatively in the starved and stressed patient. We compared plasma concentrations of parenteral paracetamol given preoperatively and oral paracetamol when given as premedication. Patients scheduled for elective ear; nose and throat surgery or orthopaedic surgery were randomised to receive either oral or intravenous paracetamol as preoperative medication. The oral dose was given 30 minutes before induction of anaesthesia and the intravenous dose given pre-induction. All patients were given a standardised anaesthetic by the same specialist anaesthetist who took blood for paracetamol concentrations 30 minutes after the first dose and then at 30 minute intervals for 240 minutes. Therapeutic concentrations of paracetamol were reached in 96% of patients who had received the drug parenterally, and 67% of patients who had received it orally. Maximum median plasma concentrations were 19 mg.l(-1) (interquartile range 15 to 23 mg.l(-1)) and 13 mg.l(-1) (interquartile range 0 to 18 mg.l(-1)) for the intravenous and oral group respectively. The difference between intravenous and oral groups was less marked after 150 minutes but the intravenous preparation gave higher plasma concentrations throughout the study period. It can be concluded that paracetamol gives more reliable therapeutic plasma concentrations when given intravenously.

  20. A comparison of serum antivenom concentrations after intravenous and intramuscular administration of redback (widow) spider antivenom

    PubMed Central

    Isbister, Geoffrey K; O'Leary, Margaret; Miller, Mark; Brown, Simon G A; Ramasamy, Sharmaine; James, Rosemary; Schneider, Jennifer S

    2008-01-01

    AIMS There are no studies measuring antivenom concentrations following intramuscular administration. This study aimed to compare antivenom concentrations following intravenous and intramuscular administration of redback spider antivenom (RBSAV). METHODS Twenty patients recruited to a controlled trial comparing intramuscular and intravenous administration of antivenom had serial blood samples collected at 30 min intervals for 2 h after the administration of one or two doses of antivenom. Antivenom concentration was measured using an enzyme immunoassay. RESULTS Ten patients received intramuscular antivenom but antivenom could not be detected in serum after either one or two vials, at any time point. The median time of the final sample after commencement of antivenom treatment in these patients was 3.2 h (1.8–5 h). Ten patients received intravenous antivenom (three one vial and seven two or more vials) and antivenom was detected in all patients. CONCLUSIONS RBS AV given by the intramuscular route is unlikely to be effective in the treatment of redback (widow) spider bite. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Widow spider antivenoms, including redback spider antivenom, are often given by the intramuscular route. No studies have measured widow spider antivenom following intramuscular or intravenous antivenom. WHAT THIS STUDY ADDS Intramuscular redback spider antivenom is not detectable in serum for at least 3–5 h after treatment. Intravenous antivenom is detectable 30 min after intravenous infusion. Intramuscular antivenom may not be an effective administration route. PMID:18171334

  1. Disaccharides in urine samples as markers of intravenous abuse of methadone and buprenorphine.

    PubMed

    Jungen, Hilke; Andresen-Streichert, Hilke; Müller, Alexander; Iwersen-Bergmann, Stefanie

    2013-01-01

    Methadone and buprenorphine are commonly used as oral substitutes in opiate maintenance programs to treat persons who are dependent on heroin. During these programs, patients are not allowed to continue using illicit drugs. Abstinence can easily be monitored by urine tests with immunochemical methods. It is well known that the intravenous abuse of heroin substitutes like methadone or buprenorphine has become common as well. The methadone-prescribing physician has no opportunity to check whether the opiate maintenance treatment patient takes his substitution medicines orally as intended or continues with his intravenous misuse now substituting the methadone instead of injecting heroin. In Germany, substitutes are available as liquids and tablets that contain carbohydrates as adjuvants. Sucrose is used to increase viscosity in liquids, while lactose is needed for pressing tablets (e.g., Methaddict® and Subutex®). In case of oral ingestion, disaccharides are broken down into monosaccharides by disaccharidases in the small intestine. These monosaccharides are absorbed into the blood stream by special monosaccharide transporters. Disaccharidases do not exist in blood, thus sucrose and lactose are not split if substitute medicines are injected intravenously. Our assumption, therefore, was that they are excreted unchanged in urine. We investigated a method for the detection of disaccharides in urine as markers of intravenous abuse of substitutes. Urine samples of 26 intravenous substitute abusers showed all positive results for lactose (76.9%) and/or sucrose (73.1%). The method is assumed to be useful to detect intravenous abuse of substitutes.

  2. Aminothiol Receptors for Decorporation of Intravenously Administered 60Co in the Rat

    SciTech Connect

    Levitskaia, Tatiana G.; Morris, James E.; Creim, Jeffrey A.; Woodstock, Angela D.; Luders, Teresa; Curry, Terry L.; Thrall, Karla D.

    2010-01-01

    The reported investigation provides a comparison of the oral decorporation efficacy of L-glutathione (GSH), L-cysteine (Cys), and a liposomal GSH formulation (ReadiSorb) toward systemic cobalt-60 (60Co) to that observed following intravenous administration of GSH and Cys in F344 rats. L-histidine (His) was tested intravenously to compare in vivo efficacy of the aminothiol GSH and Cys chelators with that of aminoimidazole (His) chelator. 60Co was administered to animals by intravenous injection, followed by intravenous or oral gavage doses of a chelator repeated at 24 hour intervals for a total of 5 doses. The results suggest that GSH and Cys are potent decorporation agents for 60Co in the rat model, although the efficacy of treatment depends largely on systemic availability of a chelator. The intravenous GSH or Cys were most effective in reducing tissue 60Co levels and in increasing excretion of radioactivity compared to control animals. Liposomal encapsulation was found to markedly enhance the oral bioavailability of GSH compared to non-formulated GSH. Oral administration of ReadiSorb reduced 60Co levels in nearly all tissues by 12-43% compared to that observed for non-formulated GSH. Efficacy of oral Cys was only slightly reduced in comparison with intravenous Cys. Further studies to optimize the dosing regimen in order to maximize decorporation efficiency are warranted.

  3. Effect of intravenous fructose on the P-31 MR spectrum of the liver: dose response in healthy volunteers.

    PubMed

    Terrier, F; Vock, P; Cotting, J; Ladebeck, R; Reichen, J; Hentschel, D

    1989-05-01

    Dynamic phosphorus-31 magnetic resonance (MR) spectroscopy of the liver after intravenous administration of fructose has been suggested as a test of liver function. To establish dose-response curves of the phosphorus metabolites in the normal human liver, each of four healthy volunteers was given two to four different fructose doses on separate days: 62.5, 125, 250, 375, or 500 mg per kilogram of body weight. P-31 MR spectra of the liver were acquired with a 2-T whole-body magnetic, both before and after fructose administration, at 2.5-minute intervals over at least 30 minutes. The fructose load caused a significant, linearly dose-dependent accumulation of phosphomonoesters (r = .72, P less than .01) and a decrease in inorganic phosphate (r = .78, P less than .005) and adenosine triphosphate (r = .73, P less than .01). On the basis of these experiments, dynamic P-31 MR spectroscopy seems promising in the assessment of liver function.

  4. Simultaneous oral therapeutic and intravenous 14C‐microdoses to determine the absolute oral bioavailability of saxagliptin and dapagliflozin

    PubMed Central

    Boulton, David W.; Kasichayanula, Sreeneeranj; Keung, Chi Fung (Anther); Arnold, Mark E.; Christopher, Lisa J.; Xu, Xiaohui (Sophia); LaCreta, Frank

    2013-01-01

    Aim To determine the absolute oral bioavailability (Fp.o.) of saxagliptin and dapagliflozin using simultaneous intravenous 14C‐microdose/therapeutic oral dosing (i.v.micro + oraltherap). Methods The Fp.o. values of saxagliptin and dapagliflozin were determined in healthy subjects (n = 7 and 8, respectively) following the concomitant administration of single i.v. micro doses with unlabelled oraltherap doses. Accelerator mass spectrometry and liquid chromatography‐tandem mass spectrometry were used to quantify the labelled and unlabelled drug, respectively. Results The geometric mean point estimates (90% confidence interval) Fp.o. values for saxagliptin and dapagliflozin were 50% (48, 53%) and 78% (73, 83%), respectively. The i.v.micro had similar pharmacokinetics to oraltherap. Conclusions Simultaneous i.v.micro + oraltherap dosing is a valuable tool to assess human absolute bioavailability. PMID:22823746

  5. Hemorrhagic Fever Occurs After Intravenous, But Not After Intragastric, Inoculation of Rhesus Macaques With Lymphocytic Choriomeningitis Virus

    PubMed Central

    Lukashevich, Igor S.; Djavani, Mahmoud; Rodas, Juan D.; Zapata, Juan C.; Usborne, Amy; Emerson, Carol; Mitchen, Jacque; Jahrling, Peter B.; Salvato, Maria S.

    2008-01-01

    Arenaviruses can cause hemorrhagic fever and death in primates and guinea pigs, but these viruses are not highly pathogenic for most rodent carriers. In the United States, arenaviruses precipitated outbreaks of hepatitis in captive monkeys, and they present an emerging health threat in the tropical areas of Africa and South America. We describe infection of rhesus macaques with the prototype arenavirus, lymphocytic choriome-ningitis virus (LCMV), using the WE strain that has been known to cause both encephalopathy and multifocal hemorrhage. Five macaques were inoculated: two by the intravenous (i.v.) and three by the intragastric (i.g.) route. Whereas the two i.v.-inoculated monkeys developed signs and lesions consistent with fatal hemorrhagic fever, the i.g.-inoculated monkeys had an attenuated infection with no disease. Pathological signs of the primate i.v. infection differ significantly from guinea pig arenavirus infections and make this a superior model for human viral hemorrhagic disease. PMID:11992578

  6. Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in children.

    PubMed Central

    Hayton, W L; Walstad, R A; Thurmann-Nielsen, E; Kufaas, T; Kneer, J; Ambros, R J; Rugstad, H E; Monn, E; Bodd, E; Stoeckel, K

    1991-01-01

    The pharmacokinetics of cefetamet were determined after intravenous (i.v.) administration of cefetamet and oral administration of cefetamet pivoxil syrup to patients between the ages of 3 and 12 years. The patients were hospitalized for reconstructive urological surgery; to prevent infection, prophylactic i.v. cefetamet was administered on the day of surgery and oral cefetamet pivoxil was administered 2 days later. After i.v. administration, the mean (+/- standard deviation) half-life of cefetamet was 1.97 +/- 0.60 h (n = 18), which was different from the 2.46 +/- 0.33 h reported for nine adults (22 to 68 years old) in a previous study. The average values for the mean residence times were 2.35 +/- 0.94 and 2.83 +/- 0.34 h and the average values for the fraction of the dose eliminated unchanged in the urine were 79.9% +/- 8.99% and 80% +/- 11% in children and adults, respectively. Plots of mean systemic clearance and steady-state volume of distribution versus body weight for the children and comparative adults were linear on log-log coordinates, and the slopes of the plots were 0.661 and 0.880, respectively. These slope values suggested that mean systemic clearance values per unit of body surface area were similar in children and adults and that maintenance doses for children should be the adult maintenance dose multiplied by the child's surface area divided by 1.73 m2. The mean (+/- standard deviation) oral bioavailabilities of cefetamet pivoxil were 49.3% +/- 15.7% in 3- to 7-year-old children who received a 500-mg dose and 37.9% +/- 10.0% in 8- to 12-year-old children who received a 1,000-mg dose. These values were not different from that observed in the adult group after two 500-mg tablets. Likewise, the peak concentration of cefetamet in plasma and its time of occurrence in children were in line with the values which have been observed for adults. PMID:2069377

  7. Pharmacokinetics of flunixin in mature heifers following multiple intravenous administration.

    PubMed

    Jaroszewski, J; Jedziniak, P; Markiewicz, W; Grabowski, T; Chrostowska, M; Szprengier-Juszkiewicz, T

    2008-01-01

    The pharmacokinetics of flunixin meglumine was determined after its multiple (altogether 4 doses at 24-hours intervals) intravenous administration at a dose of 2.2 mg/kg body weight in six mature clinically healthy heifers. Plasma flunixin and its metabolite 5-hydroxyflunixin concentrations were analyzed with high-pressure liquid chromatography using an assay with a lower limit detection of 0.03 microg/ml for both substances. Plasma concentrations versus time curves were described by a two compartment open model. Mean plasma flunixin concentrations were similar on day 1 and 4, and than rapidly decreased (within 2 hours) from initial concentrations higher than 10 microg/ml to the concentrations lower than 1 microg/ml. The distribution phase of flunixin was short (t0.5 alpha = 0.29 +/- 0.16 and 0.18 +/- 0.04 on day 1 and 4, respectively) and the elimination phase was more prolonged (t0.5 beta = 3.30 +/- 0.60 and 3.26 +/- 0.22 on day 1 and 4, respectively). The mean residence time of flunixin was similar on day 1 (1.83 +/- 0.83) and 4 (1.88 +/- 0.46), and for 5-hydroxyflunixin this parameter was insignificantly (P > 0.05) higher on day 1 (5.49 +/- 2.22) as compared to that found on day 4 (3.99 +/- 2.17). The clearance of flunixin was similar on both examined days (0.23 +/- 0.12 on day 1 and 0.31 +/- 0.15 on day 4), and for 5-hydroxyflunixin was insignificantly (P > 0.05) lower on day 1 (2.37 +/- 1.21) as compared to that determined on day 4 (3.23 +/- 1.06). Our data indicate that multiple administration of flunixin did not alter significantly the parent drug and its metabolite concentrations in plasma, however may cause some small changes in pharmacokinetic parameters.

  8. A study on total intravenous anesthesia in orthognathic surgical procedures

    PubMed Central

    Vasundhar, P. L.; Sadhasivam, Gokkulakrishnan; Bhushan, Satya; Kalyan, Siva; Chiang, Kho Chai

    2016-01-01

    Aims and Objective: To assess the use of propofol for induction and maintenance of anaesthesia among patients undergoing various combinations of orthognathic surgical procedures. Materials and Methods: Following Preoperative evaluation, patients were given Fentanyl (2 micrograms/kg) intravenously. Induction (2 mg/kg) and maintenance (10 mg/kg/hr) of anaesthesia was achieved by Propofol infusion. Blood Pressure and heart rate were maintained at >70 or 80 mm Hg and >50 respectively and were monitored continuously. Infusion was stopped approximately 30 to 40 minutes before the end of surgery. Immediate recovery recorded and was assessed. Results: The average duration of anaesthesia and surgery were found to be 4 hrs 28 min (SD= 1 hr. 35 min) and 4 hrs 3 min (SD=1 hr 38 min). None of the patients experienced pain on injection of induction agent. No significant change was observed in the mean heart rate and mean BP at different time intervals from baseline value to 30 minutes after the recovery. The average time taken to obey simple commands after stopping Propofol infusion was 42.60 ± 9.09 min. Time taken for spontaneous eye opening, full orientation and to count backwards was 43.45 ± 9.11, 47.85 ± 8.18 and 50.9 ± 9.14 respectively. Face-Hand test performed at 15 min after extubation was positive in all the patients. The mean Aldrete score at 15 min after extubation was 11.65 ± 0.75. The mean value of unaided sitting time for at least 2 min was after 119.00 ± 20.56 min. The average score of picture card test, time taken in “picking up matches” test, Ball bearing test, time taken to walk and to void urine were 5.80 ± 1.47, 67.95 ± 5.72, 9.80 ± 2.57, 172.75 ± 39.25 and 163.75 ± 55.96 respectively. Ninety percent of the patients were amenable for a repeat of this anaesthetic using the same regime but 10% of them did not answer anything. Seven patients (35%) had chills post-operatively. Conclusion: Propofol is an excellent anaesthetic for day care procedures

  9. Stability of Reconstituted Telavancin Drug Product in Frozen Intravenous Bags

    PubMed Central

    Wong, Anissa; Raquinio, Elvira; Nguyen, Alice

    2015-01-01

    Background and Objective: Intravenous (IV) infusions of telavancin for injection are generally administered in-hospital, but in some circumstances they may be administered in an outpatient environment. In that setting, antibiotics may be premixed and frozen. This study determined the chemical stability of nonpreserved telavancin in various commonly used reconstitution diluents stored in IV bags (polyvinyl chloride [PVC] and PVC-free) at -20°C (-4°F) without light. Methods: Telavancin (750 mg/vial) was reconstituted with 5% dextrose injection USP (D5W) or 0.9% sodium chloride injection USP (NS) to obtain drug solutions at approximately 15 mg/mL. Infusion solutions of telavancin at diluted concentrations of 0.6 mg/mL and 8.0 mg/mL covering the range utilized in clinical practice were prepared in both PVC and PVC-free IV bags using D5W or NS solutions. The infusion solutions were stored under frozen conditions (-20°C ± 5°C [-4°F ± 41°F]) and the chemical stability was evaluated for up to 32 days. Telavancin concentration, purity, and degradant levels were determined using a stability-indicating high-performance liquid chromatography (HPLC) method. Results: Telavancin IV infusion solutions in D5W or NS at 0.6 mg/mL and 8 mg/mL and stored at -20°C (-4°F) met the chemical stability criteria when tested on days 0, 7, 14, and 32. The assayed telavancin concentration at each time point was within 97% to 103% of the initial mean assay value. The total degradants quantified by the HPLC stability-indicating method did not show any significant change over the 32-day study period. Conclusion: Telavancin IV infusion solutions (in D5W or NS) in both PVC and PVC-free IV bags were stable for at least 32 days when stored at -20°C (-4°F) without light. These results provide prolonged frozen stability data further to that previously established for 7 days under refrigerated conditions (2°C-8°C [36°F -46°F]), and for 12 hours at room temperature when diluted into IV bags

  10. The use of intravenous immunoglobulin in immune tolerance induction in inherited haemophilia A: a single-centre experience and a review of literature.

    PubMed

    Kubisz, Peter; Hollý, Pavol; Staško, Ján; Plameňová, Ivana

    2015-09-01

    The immune tolerance induction is the treatment of choice for the eradication of factor VIII inhibitors, a serious complication of inherited haemophilia A. Despite the preferred treatment of patients with good prognosis and testing of different regimens, the immune tolerance is achieved in 70-80%. Several modifications of regimens including the addition of immunomodulatory agents were proposed in order to improve immune tolerance induction (ITI) outcome. Intravenous immunoglobulin has complex immunomodulatory properties and has been used in immune tolerance induction since the introduction of Malmö regimen in the 1980s. The aim of the work is to evaluate the published evidence of its use in ITI in haemophilia A. In addition, the authors' own experience with a high-dose regimen using human plasma-derived factor VIII containing von Willebrand factor and pulsed IVIg is reported. The course of three patients with severe inherited haemophilia A and inhibitor (all high responders, two with poor prognosis, one with rescue treatment) is described. At least partial success was achieved in all patients and no adverse events attributable to intravenous immunoglobulin were observed. Despite the limited evidence, the addition of intravenous immunoglobulin appears to be a promising treatment modification for patients with poor prognosis or previous failure of immune tolerance induction.

  11. The intraocular pressure-lowering properties of intravenous paracetamol

    PubMed Central

    van den Heever, Henning; Meyer, David

    2016-01-01

    Aim The aim of this paper was to investigate the intraocular pressure (IOP)-changing properties of a single standard dose of intravenous (IV) paracetamol and compare it to that of topical timolol, oral acetazolamide, and no treatment. Methods A prospective, randomized, investigator-blind, parallel-group study was conducted in 73 eyes of 52 subjects. Subjects received a single dose of IV paracetamol (1 g), oral acetazolamide (250 mg), topical timolol (0.5%, one drop), or no treatment. Baseline IOP was measured, and the measurement was repeated at 1, 2, 4, and 6 hours after treatment. Results Paracetamol reduced IOP from baseline by −10.8% (95% confidence interval [CI]: −4.9% to −16.8%, P=0.146) at 1 hour, −13.3% (95% CI: −8.3% to −18.4%, P=0.045) at 2 hours, −11.8% (95% CI: −5.5% to −18.4%, P=1.000) at 4 hours, and −23.9% (95% CI: −17.8% to −30.1%, P=0.006) at 6 hours after treatment. In the no-treatment group, the change was −2.9% (95% CI: +1.0% to −6.7%, P= referent) at 1 hour, −2.1% (95% CI: +2.9% to −7.2%, P= referent) at 2 hours, −7.6% (95% CI: −3.9% to −11.2%, P= referent) at 4 hours, and −6.9% (95% CI: −3.6% to −10.2%, P= referent) at 6 hours. Acetazolamide reduced IOP by −18.8% (95% CI: −12.7% to −24.8%, P=0.000) at 1 hour, −26.2% (95% CI: −18.2% to −34.2%, P=0.001) at 2 hours, −24.6% (95% CI: −16.9% to −32.3%, P=0.000) after 4 hours, and −26.9% (95% CI: −19.6% to −34.3%, P=0.000) 6 hours after treatment. Timolol reduced IOP by −31.2% (95% CI: −26.7% to −35.7%, P=0.000) at 1 hour, −27.7% (95% CI: −20.7% to −34.8%, P=0.000) at 2 hours, −28.7% (95% CI: −21.1% to −36.2%, P=0.000) at 4 hours, and −21.3% (95% CI: −13.4% to −30.0%, P=0.030) at 6 hours after treatment. The average change in IOP for the no-treatment group was −4.8% (95% CI: −2.6% to −6.9%, P= referent). It was −15.7% (95% CI: −9.3% to −22.1%, P=0.021) for paracetamol, −23.1% (95% CI: −16.4% to

  12. A part-randomized study of intravenous oseltamivir in adolescents and adults.

    PubMed

    Várkonyi, I; Chappey, C; Giraudon, M; Burleigh, L

    2015-06-01

    Seriously ill patients with influenza may be unable to take oral medication. The safety of intravenous oseltamivir was evaluated in adults and adolescents. This prospective, part-randomized study enrolled hospitalized patients aged ≥13 years with clinical or laboratory-confirmed influenza, who started study medication within 144 h of illness onset. Patients with normal renal function received oseltamivir 100 or 200 mg every 12 h for 5 days by slow intravenous infusion. Patients with renal impairment received lower doses, appropriate to the degree of impairment. Blood samples were taken for pharmacokinetics, and nasal swabs were taken to monitor viral shedding and resistance [reverse transcription polymerase chain reaction (RT-PCR) and culture]. Adverse events (AEs) were monitored for 30 days from treatment initiation. Of the 118 patients enrolled, 103 had normal renal function. On day 1, 64 patients had laboratory-confirmed influenza. Ninety-four (80 %) patients completed 5 days of oseltamivir treatment (32 intravenous only). Sixty-eight and 13 patients reported on-treatment AEs and serious AEs (SAEs), respectively (62 and nine during intravenous dosing, respectively). For 33 and six patients, these AEs and SAEs were considered treatment-related (31 and five during intravenous dosing, respectively); 11 patients had AEs causing treatment withdrawal. Five patients died. Adequate systemic exposure to oseltamivir carboxylate (OC) was achieved at the intravenous doses tested. Oseltamivir-resistant viruses (H275Y) were detected in two patients. In seriously ill, hospitalized patients with/without renal impairment, intravenous oseltamivir was not associated with adverse safety findings at the dosages tested and achieved systemic OC exposures at least as high as the approved oral dose.

  13. Acute injury with intravenous iron and concerns regarding long-term safety.

    PubMed

    Bishu, Kalkidan; Agarwal, Rajiv

    2006-09-01

    Intravenous iron is widely used to maintain adequate iron stores and prevent iron deficiency anemia in patients with chronic kidney disease, yet concerns remain about its long-term safety with respect to oxidative stress, kidney injury, and accelerated atherosclerosis, which are the subjects of this review. Three parenteral iron formulations are available for use in the United States: Iron dextran, iron gluconate, and iron sucrose. Iron dextran, especially the high molecular form, has been linked with anaphylactoid and anaphylactic reactions, and its use has been declining. A portion of intravenous iron preparations is redox-active, labile iron available for direct donation to transferrin. In vitro tests show that commonly available intravenous iron formulations have differing capacities to saturate transferrin directly: Iron gluconate > iron sucrose > iron dextran. Intravenous iron treatment produces oxidative stress, as demonstrated by increases in plasma levels of lipid peroxidation products (malondialdehyde), at a point that is much earlier than the time to peak concentration of catalytically active iron, suggesting a direct effect of iron sucrose on oxidative stress. Furthermore, iron sucrose infusion produces endothelial dysfunction that seems to peak earlier than the serum level of free iron. Intravenous iron sucrose infusion also has been shown to produce acute renal injury and inflammation as demonstrated by increased urinary albumin, enzyme (N-acetyl-beta-glucosaminidase), and cytokine (chemokine monocyte chemoattractant protein-1) excretions. Although the long-term dangers of intravenous iron are unproved, these data call for examination of effects of intravenous iron on the potential for long-term harm in patients with chronic kidney disease.

  14. Organizational and technological correlates of nurses' trust in a smart intravenous pump.

    PubMed

    Montague, Enid; Asan, Onur; Chiou, Erin

    2013-03-01

    The aim of this study was to understand technology and system characteristics that contribute to nurses' ratings of trust in a smart intravenous pump. Nurses' trust in new technologies can influence how technologies are used. Trust in technology is defined as a person's belief that a technology will not fail them. Potential outcomes of trust in technology are appropriate trust, overtrust, distrust, and mistrust. Trust in technology is also related to several use-specific outcomes, including appropriate use and inappropriate use such as overreliance, disuse or rejection, or misuse. Understanding trust in relation to outcomes can contribute to designs that facilitate appropriate trust in new technologies. A survey was completed by 391 nurses a year after the implementation of a new smart intravenous pump. The survey assessed trust in the intravenous pump and other elements of the sociotechnical system, individual characteristics, technology characteristics, and organizational characteristics. Results show that perceptions of usefulness, safety, ease of use, and usability are related to ratings of trust in smart intravenous pumps. Other work systemfactors such as perception of work environment, age, experience, quality of work, and perception of work performance are also related to ratings of trust. Nurses' trust in smart intravenous pumps is influenced by both characteristics of the technology and the sociotechnical system. Findings from this research have implications for the design of future smart intravenous pumps and health systems. Recommendations for appropriately trustworthy smart intravenous pumps are discussed. Findings also have implications for how trust in health technologies can be measured and conceptualized in complex sociotechnical systems.

  15. Urinary excretion profiles for total morphine, free morphine, and 6-acetylmorphine following smoked and intravenous heroin.

    PubMed

    Smith, M L; Shimomura, E T; Summers, J; Paul, B D; Jenkins, A J; Darwin, W D; Cone, E J

    2001-10-01

    Heroin is one of the major target drugs in workplace drug-testing programs because of its history of abuse, liability, and continued negative social impact. This study was a comprehensive examination of pharmacokinetics, pharmacodynamics, detection times, opiate immunoassay performance, and urine excretion profiles following single doses of heroin administered to human subjects via smoking and intravenous routes. Studies of the first four components of this investigation were previously published. This article describes the urine excretion profiles. Total morphine (Tmor), free morphine (Fmor), and 6-acetylmorphine (6-AM) were measured by gas chromatography-mass spectrometry (GC-MS) in 920 urine samples collected from 11 male human subjects following single doses of heroin. Eight received intravenous doses of 3, 6, and 12 mg heroin HCI and four smoked 3.5-, 5.2-, 7-, 10.5-, or 13.9-mg doses of heroin (base). In addition, 183 urine-based blind quality-control samples were added to the study set to assess assay performance. Creatinine was also measured in each sample by a colorimetric technique. The parameters studied were not significantly dependent on route of administration. Excretion half-life mean +/- SD for Tmor was 3.11 +/- 0.30 h. Range (median) of peak urine concentrations, time to peak, time to last positive sample for low cutoff (300 ng/mL) and high cutoff (2000 ng/mL) for Tmor following lower doses (< or = 7 mg) were, respectively, 1392-9250 (3620) ng/mL, 1.2-6.2 (2.3) h, 7.4-31.9 (7.4) h, and 0-10.1 (4.3) h. Following higher doses (> 10 mg) they were 2065-29,030 (16,470) ng/mL, 2.3-9.3 (4.5) h, 10.7-53.5 (34.4) h, 2.3-22.3 (8.3) h. Fmor peaked in the same sample as Tmor. Range (median) of peak Fmor concentrations and time to last positive using a cutoff of 100 ng/mL for low and high doses were, respectively, 117-1160 (415) ng/mL, 1.2-10.1 (4.5) h and 150-2580 (1400) ng/mL, 2.3-29.1 (9.3) h. The range (median) of peak urine concentrations for 6-AM was 6

  16. Intravenous oxytocin alone for cervical ripening and induction of labour

    PubMed Central

    Alfirevic, Zarko; Kelly, Anthony J; Dowswell, Therese

    2014-01-01

    Background Oxytocin is the commonest induction agent used worldwide. It has been used alone, in combination with amniotomy or following cervical ripening with other pharmacological or non-pharmacological methods. Objectives To determine the effects of oxytocin alone for third trimester cervical ripening and induction of labour in comparison with other methods of induction of labour or placebo/no treatment. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (January 2009) and bibliographies of relevant papers. Selection criteria Randomised and quasi-randomised trials comparing intravenous oxytocin with placebo or no treatment, or with prostaglandins (vaginal or intracervical) for third trimester cervical ripening or labour induction. Data collection and analysis Two review authors independently assessed eligibility and carried out data extraction. Main results Sixty-one trials (12,819 women) are included. When oxytocin inductions were compared with expectant management, fewer women failed to deliver vaginally within 24 hours (8.4% versus 53.8%, risk ratio (RR) 0.16, 95% confidence interval (CI) 0.10 to 0.25). There was a significant increase in the number of women requiring epidural analgesia (RR 1.10, 95% CI 1.04 to 1.17). Fewer women were dissatisfied with oxytocin induction in the one trial reporting this outcome (5.9% versus 13.7%, RR 0.43, 95% CI 0.33 to 0.56). Compared with vaginal prostaglandins, oxytocin increased unsuccessful vaginal delivery within 24 hours in the two trials reporting this outcome (70% versus 21%, RR 3.33, 95% CI 1.61 to 6.89). There was a small increase in epidurals when oxytocin alone was used (RR 1.09, 95% CI 1.01 to 1.17). Most of the studies included women with ruptured membranes, and there was some evidence that vaginal prostaglandin increased infection in mothers (chorioamnionitis RR 0.66, 95% CI 0.47 to 0.92) and babies (use of antibiotics RR 0.68, 95% CI 0.53 to 0.87). These data should be

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

    PubMed Central

    Jin, Jing-fen; Zhu, Ling-ling; Chen, Meng; Xu, Hui-min; Wang, Hua-fen; Feng, Xiu-qin; Zhu, Xiu-ping; Zhou, Quan

    2015-01-01

    Background 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 immu-noglobulin, 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 governing the choice of injection route. Safety and efficacy must be the preferred principles to be considered (eg, epinephrine should be given intramuscularly during an episode of systemic anaphylaxis). If the safety and efficacy of two injection routes are equivalent, clinicians should consider more about patient preference and

  18. New primate model for the study of intravenous thrombotic potential and its modification

    SciTech Connect

    Shoenfeld, N.A.; Yeager, A.; Connolly, R.; Ramberg, K.; Forgione, L.; Giorgio, A.; Valeri, C.R.; Callow, A.D.

    1988-07-01

    Advances in venous reconstruction have been limited by inherent venous thrombogenicity and the absence of a suitable prosthetic material for use in the venous system. We have designed an in vivo experimental model to evaluate early blood-material interactions within the venous system and to quantitate drug efficacy in the alteration of platelet function and fibrin deposition in the baboon. An 8F catheter was placed percutaneously in the femoral vein of an adult male baboon. Indium 111-labeled autogenous platelets or iodine 125-labeled human fibrinogen was infused before the introduction, into the inferior vena cava, of a linear array of 5 x 15 mm alternating Dacron and polytetrafluoroethylene samples attached to a benzalkonium-heparin-treated guide wire. At 60 or 120 minutes the samples were removed and a 1 ml aliquot of blood was drawn. The materials and blood samples were counted in a gamma well counter, and the material counts were normalized to the circulating label present in the 1 ml blood sample. The experiment was repeated after pretreatment with heparin, aspirin, or dextran. Whole blood clotting times and bleeding times were monitored. The results showed decreased platelet and fibrin deposition on polytetrafluoroethylene when compared with Dacron in the venous system. Aspirin, heparin, and dextran were all found to decrease platelet and fibrin deposition onto intravenously placed graft material samples (p less than 0.05, Student's t test). The data confirm the ability of the model to evaluate quantitatively anticoagulants, antiplatelet agents, and prospective graft materials for use in venous reconstructions.

  19. Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses.

    PubMed

    Knych, H K; Arthur, R M; Mitchell, M M; Holser, I; Poppenga, R; Smith, L L; Helm, M N; Sams, R A; Gaskill, C L

    2015-07-01

    Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were administered a single intravenous dose of cobalt chloride or cobalt gluconate and serum and urine samples collected for up to 10 days post administration. Cobalt concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) and pharmacokinetic parameters determined. Additional blood samples were collected for measurement of equine EPO concentrations as well as to assess any effects on red blood cell parameters. Horses were observed for adverse effects and heart rate monitored for the first 4 h post administration. Cobalt was characterized by a large volume of distribution (0.939 L/kg) and a prolonged gamma half-life (156.4 h). Cobalt serum concentrations were still above baseline values at 10 days post administration. A single administration of cobalt had no effect on EPO concentrations, red blood cell parameters or heart rate in any of the horses studied and no adverse effects were noted. Based on the prolonged gamma half-life and prolonged residence time, regulators should be able to detect administration of a single dose of cobalt to horses.

  20. Deriving a provisional tolerable intake for intravenous exposure to silver nanoparticles released from medical devices.

    PubMed

    Savery, Laura C; Viñas, René; Nagy, Amber M; Pradeep, Prachi; Merrill, Stephen J; Hood, Alan M; Malghan, Subhas G; Goering, Peter L; Brown, Ronald P

    2017-04-01

    Silver nanoparticles (AgNP) are incorporated into medical devices for their anti-microbial characteristics. The potential exposure and toxicity of AgNPs is unknown due to varying physicochemical particle properties and lack of toxicological data. The aim of this safety assessment is to derive a provisional tolerable intake (pTI) value for AgNPs released from blood-contacting medical devices. A literature review of in vivo studies investigating critical health effects induced from intravenous (i. v.) exposure to AgNPs was evaluated by the Annapolis Accords principles and Toxicological Data Reliability Assessment Tool (ToxRTool). The point of departure (POD) was based on an i. v. 28-day repeated AgNP (20 nm) dose toxicity study reporting an increase in relative spleen weight in rats with a 5% lower confidence bound of the benchmark dose (BMDL05) of 0.14 mg/kg bw/day. The POD was extrapolated to humans by a modifying factor of 1,000 to account for intraspecies variability, interspecies differences and lack of long-term toxicity data. The pTI for long-term i. v. exposure to 20 nm AgNPs released from blood-contacting medical devices was 0.14 μg/kg bw/day. This pTI may not be appropriate for nanoparticles of other physicochemical properties or routes of administration. The methodology is appropriate for deriving pTIs for nanoparticles in general.

  1. ELISA measurement of specific antibodies to phosphorylated tau in intravenous immunoglobulin products.

    PubMed

    Loeffler, David A; Klaver, Andrea C; Coffey, Mary P

    2015-10-01

    The therapeutic effects of intravenous immunoglobulin (IVIG) products were recently studied in Alzheimer's disease (AD) patients. Pilot studies produced encouraging results but phase II and III trials gave disappointing results; a further study is in progress. IVIG products contain antibodies to tau protein, the main component of neurofibrillary tangles (NFTs). The tau used to detect IVIG's anti-tau antibodies in previous studies was non-phosphorylated recombinant human tau-441, but NFT-associated tau is extensively phosphorylated. The objective of this study was to determine if various IVIG products contain specific antibodies to phosphorylated tau (anti-pTau antibodies). ELISAs were used to evaluate binding of six IVIG products to a 12 amino acid peptide, tau 196-207, which was phosphorylated ("pTau peptide") or non-phosphorylated ("non-pTau peptide") at Serine-199 and Serine-202. Both amino acid residues are phosphorylated in AD NFTs. Each IVIG's "anti-pTau antibody ratio" was calculated by dividing its binding to the pTau peptide by its binding to the non-pTau peptide. Seven experiments were performed and data were pooled, with each experiment contributing one data point from each IVIG product. Mean anti-pTau antibody ratios greater than 1.0, suggesting specific antibodies to phosphorylated tau, were found for three IVIG products. Because administration of antibodies to phosphorylated tau has been found to reduce tau-associated pathology in transgenic mouse models of tauopathy, increasing the levels of anti-pTau antibodies, together with other selected antibodies such as anti-Aβ, in IVIG might increase its ability to slow AD's progression.

  2. Intravenous Immunglobulin Binds Beta Amyloid and Modifies Its Aggregation, Neurotoxicity and Microglial Phagocytosis In Vitro

    PubMed Central

    Cattepoel, Susann; Schaub, Alexander; Ender, Miriam; Gaida, Annette; Kropf, Alain; Guggisberg, Ursula; Nolte, Marc W.; Fabri, Louis; Adlard, Paul A.; Finkelstein, David I.; Bolli, Reinhard; Miescher, Sylvia M.

    2013-01-01

    Intravenous Immunoglobulin (IVIG) has been proposed as a potential therapeutic for Alzheimer's disease (AD) and its efficacy is currently being tested in mild-to-moderate AD. Earlier studies reported the presence of anti-amyloid beta (Aβ) antibodies in IVIG. These observations led to clinical studies investigating the potential role of IVIG as a therapeutic agent in AD. Also, IVIG is known to mediate beneficial effects in chronic inflammatory and autoimmune conditions by interfering with various pathological processes. Therefore, we investigated the effects of IVIG and purified polyclonal Aβ -specific antibodies (pAbs-Aβ) on aggregation, toxicity and phagocytosis of Aβ in vitro, thus elucidating some of the potential mechanisms of action of IVIG in AD patients. We report that both IVIG and pAbs-Aβ specifically bound to Aβ and inhibited its aggregation in a dose-dependent manner as measured by Thioflavin T assay. Additionally, IVIG and the purified pAbs-Aβ inhibited Aβ-induced neurotoxicity in the SH-SY5Y human neuroblastoma cell line and prevented Aβ binding to rat primary cortical neurons. Interestingly, IVIG and pAbs-Aβ also increased the number of phagocytosing cells as well as the amount of phagocytosed fibrillar Aβ by BV-2 microglia. Phagocytosis of Aβ depended on receptor-mediated endocytosis and was accompanied by upregulation of CD11b expression. Importantly, we could also show that Privigen dose-dependently reversed Aβ-mediated LTP inhibition in mouse hippocampal slices. Therefore, our in vitro results suggest that IVIG may have an impact on different processes involved in AD pathogenesis, thereby promoting further understanding of the effects of IVIG observed in clinical studies. PMID:23696796

  3. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile

    PubMed Central

    Rafiei, Pedram; Haddadi, Azita

    2017-01-01

    Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug’s pharmacokinetics related to the conventional formulation. Poly(lactide-co-glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs’ long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA–PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel’s pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs. PMID:28184163

  4. Transfer of antibodies across the placenta and in breast milk from mothers on intravenous immunoglobulin.

    PubMed

    Palmeira, Patricia; Costa-Carvalho, Beatriz T; Arslanian, Christina; Pontes, Gerlândia N; Nagao, Aparecida T; Carneiro-Sampaio, Magda M S

    2009-09-01

    We studied the levels of immunoglobulins in colostrum, milk and sera from two common variable immunodeficiency (CVID) mothers (M1 and M2), and in sera from their newborn infants. During pregnancy they continued intravenous immunoglobulin therapy (IVIG). Antibody levels from maternal and cord blood collected at delivery and colostrum and milk, collected on the 3rd and 7th post-partum days, respectively, were analyzed. Although cord/maternal blood ratios of total immunoglobulins and subclasses, as well as specific antibodies differed between M1 and M2, both showed good placental transfer of anti-protein and anti-polysaccharide antibodies, despite lower cord/maternal blood ratios in M2. Anti-Streptococcus pneumoniae antibody avidity indexes were similar between paired maternal and cord serum. Both mothers' colostrum and milk samples showed only traces of IgA, and IgM and IgG levels in colostrum were within normal range in M1, whereas M2 presented elevated IgG and low IgM levels, when compared with healthy mothers. The study of colostrum and milk activity showed that they strongly inhibited enteropathogenic Escherichia coli adhesion in vitro. CVID patients must be informed about the relevance of regular IVIG administration during pregnancy, not only for their own health but also for their immune immature offspring. Breast-feeding should be encouraged as colostra from these CVID patients strongly inhibited E. coli adhesion to human epithelial cells thus providing immunological protection plus nutritional and psychological benefits for the infant.

  5. Augmented reality intravenous injection simulator based 3D medical imaging for veterinary medicine.

    PubMed

    Lee, S; Lee, J; Lee, A; Park, N; Lee, S; Song, S; Seo, A; Lee, H; Kim, J-I; Eom, K

    2013-05-01

    Augmented reality (AR) is a technology which enables users to see the real world, with virtual objects superimposed upon or composited with it. AR simulators have been developed and used in human medicine, but not in veterinary medicine. The aim of this study was to develop an AR intravenous (IV) injection simulator to train veterinary and pre-veterinary students to perform canine venipuncture. Computed tomographic (CT) images of a beagle dog were scanned using a 64-channel multidetector. The CT images were transformed into volumetric data sets using an image segmentation method and were converted into a stereolithography format for creating 3D models. An AR-based interface was developed for an AR simulator for IV injection. Veterinary and pre-veterinary student volunteers were randomly assigned to an AR-trained group or a control group trained using more traditional methods (n = 20/group; n = 8 pre-veterinary students and n = 12 veterinary students in each group) and their proficiency at IV injection technique in live dogs was assessed after training was completed. Students were also asked to complete a questionnaire which was administered after using the simulator. The group that was trained using an AR simulator were more proficient at IV injection technique using real dogs than the control group (P ≤ 0.01). The students agreed that they learned the IV injection technique through the AR simulator. Although the system used in this study needs to be modified before it can be adopted for veterinary educational use, AR simulation has been shown to be a very effective tool for training medical personnel. Using the technology reported here, veterinary AR simulators could be developed for future use in veterinary education.

  6. A Novel and Effective Balanced Intravenous-Inhalant Anaesthetic Protocol in Swine by Using Unrestricted Drugs

    PubMed Central

    Calzetta, Luigino; Rossi, Piero; Bove, Pierluigi; Alfonsi, Pietro; Bonizzi, Luigi; Roncada, Paola; Bernardini, Roberta; Ricciardi, Edoardo; Montuori, Mauro; Pistocchini, Elena; Mauti, Paolo; Mattei, Maurizio

    2014-01-01

    Nowadays, because of increasing employment of swine for experimental studies and medical training, it is hopeful to investigate novel and effective anaesthetic protocols for preserving the animal welfare in medical investigation and concurrently improving the quality of research. Therefore, the aim of this study was to investigate a novel and effective anaesthetic protocol in swine undergoing major surgery, by translating know-how of combined anaesthesia from human protocols. Seven landrace swine were anaesthetized for three hours by a combined trial anaesthetic protocol (sedation: medetomidine, acepromazine, atropine and tramadol; induction: propofol, medetomidine and acepromazine; anaesthesia: isofluorane, propofol, medetomidine and acepromazine) and both clinical and haemodynamic parameters were compared with those of five swine anaesthetized with a control protocol (sedation: diazepam, ketamine and atropina; induction: diazepam and ketamine; anaesthesia: isofluorane). Both cardiac frequency (CF) and mean blood pressure (MBP) were significantly (P<0.05) more stable in trial protocol (CF: 78.3 ± 4.6-81.1 ± 5, MBP: 63.9 ± 10.7-96.4 ± 13.0) compared to control protocol (CF: 93.7 ± 5.5-102.5 ± 8.5, MBP: 71.0 ± 6.6-108.7 ± 7.2). The body temperature remained stable in trial protocol (°C: 36.9 ± 0.7-37.2 ± 0.3) compared to control anaesthesia (°C: 36.4 ± 0.3-37.3 ± 0.2, P<0.05). Haematosis improved undergoing combined anaesthesia (+2%, P<0.05) whereas did not change in control animals. There were no differences in respiratory rate between trial and control protocols. This study demonstrates that the proposed balanced intravenous-inhalant protocol permits to carry out a very effective, stable and safe anaesthesia in swine undergoing deep anaesthesia. PMID:25030879

  7. Pharmacokinetics of ketorolac tromethamine in horses after intravenous, intramuscular, and oral single-dose administration.

    PubMed

    Bianco, A W; Constable, P D; Cooper, B R; Taylor, S D

    2016-04-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are an integral component of equine analgesia, yet currently available NSAIDs are both limited in their analgesic efficacy and have adverse effects. The NSAID ketorolac tromethamine (KT) is widely used in humans as a potent morphine-sparing analgesic drug but has not been fully evaluated in horses. The purpose of this study was to determine the pharmacokinetic profile of KT in horses after intravenous (i.v.), intramuscular (i.m.), and oral (p.o.) administration. Nine healthy adult horses received a single 0.5-mg/kg dose of KT via each route of administration. Plasma was collected up to 48 h postadministration and analyzed for KT concentration using HPLC/MS/MS. Noncompartmental analysis of i.v. dosage indicated a mean plasma clearance of 8.4 (mL/min)/kg and an estimated mean volume of distribution at steady-state of 0.77 L/kg. Noncompartmental analysis of i.v., i.m., and p.o. dosages indicated mean residence times of 2.0, 2.6, and 7.1 h, respectively. The drug was rapidly absorbed after i.m. and p.o. administration, and mean bioavailability was 71% and 57% for i.m. and p.o. administration, respectively. Adverse effects were not observed after i.v., i.m., and p.o. administration. More studies are needed to evaluate the analgesic and anti-inflammatory properties of KT in horses.

  8. Alterations in the Striatal Dopamine System During Intravenous Methamphetamine Exposure: Effects of Contingent and Noncontingent Administration

    PubMed Central

    Laćan, Goran; Hadamitzky, Martin; Kuczenski, Ronald; Melega, William P.

    2014-01-01

    The continuing spread of methamphetamine (METH) abuse has stimulated research aimed at understanding consequences of its prolonged exposure. Alterations in nigrostriatal dopamine (DA) system parameters have been characterized in experimental studies after discontinuation of long term METH but fewer studies have included similar assessments during METH exposure. Here, we report METH plasma pharmacokinetics and striatal DA system alterations in rat after noncontingent and contingent METH administration for 7.5 weeks. Escalating METH exposure was delivered by dynamic infusion (DI) that incorporated a ‘humanized’ plasma METH half life, or by intravenous self-administration (IVSA) that included binge intakes. Kinetic modeling of DI and IVSA for 24 h periods during the final week of METH exposure showed that plasma METH levels remained between 0.7–1.5 μM. Animals were sacrificed during their last METH administration for autoradiography assessment using [3H]ligands and D2 agonist-induced [35S]GTPγS binding. DA transporter binding was decreased (DI, 34%; IVSA, 15%) while vesicular monoamine transporter binding and substantia nigra DA cell numbers were unchanged. Decreases were measured for D2 receptor (DI and IVSA, 15–20%) and [35S]GTPγS binding (DI, 35%; IVSA, 18%). These similar patterns of DI and IVSA associated decreases in striatal DA markers reflect consequences of cumulative METH exposure and not the drug delivery method. For METH IVSA, individual differences were observed, yet each animal’s total intake was similar within and across three 24 h binges. IVSA rodent models may be useful for identifying molecular mechanisms that are associated with METH binges in humans. PMID:23417852

  9. SAFETY AND UTILITY OF I.V. FAT EMULSION FOR HUMAN INTRAVENOUS ADMINISTRATION.

    DTIC Science & Technology

    The initial clinical experiences of our group with a European fat emulsion called Intralipid is reported. This emulsion is composed of soy bean oil...failed to show correlation between febrile response and rapidity with which clearing of the emulsion occurred. It is concluded that Intralipid is not a safe or suitable product for routine clinical use. (Author)

  10. Aripiprazole effects on self-administration and pharmacodynamics of intravenous cocaine and cigarette smoking in humans.

    PubMed

    Lofwall, Michelle R; Nuzzo, Paul A; Campbell, Charles; Walsh, Sharon L

    2014-06-01

    Aripiprazole is a partial agonist at dopamine (D2) and serotonin (5-HT1a) receptors and 5-HT2 antagonist. Because cocaine affects dopamine and serotonin, this study assessed whether aripiprazole could diminish the reinforcing efficacy of cocaine. Secondary aims evaluated aripiprazole on ad lib cigarette smoking and with a novel 40-hr smoking abstinence procedure. Adults with regular cocaine and cigarette use completed this inpatient double blind, randomized, placebo-controlled mixed-design study. A placebo lead-in was followed by randomization to aripiprazole (0, 2 or 10 mg/day/p.o.; n = 7 completed/group). Three sets of test sessions, each consisting of 3 cocaine sample-choice (i.e., self-administration) sessions and 1 dose-response session, were conducted (once during the lead-in and twice after randomization). Sample sessions tested each cocaine dose (0, 20 and 40 mg/70 kg, i.v.) in random order; subjective, observer-rated and physiologic outcomes were collected. Later that day, participants chose between the morning's sample dose or descending amounts of money over 7 trials. In dose response sessions, all doses were given 1 hr apart in ascending order for pharmacodynamic and pharmacokinetic assessment. Two sets of smoking topography sessions were conducted during the lead-in and after randomization; 1 with and 1 without 40 hr of smoking abstinence. Number of ad lib cigarettes smoked during non-session days was collected. Cocaine produced prototypic effects, but aripiprazole did not significantly alter these effects or smoking outcomes. The smoking abstinence procedure reliably produced nicotine withdrawal and craving and increased smoking modestly. These data do not support further investigation of aripiprazole for cocaine or tobacco use disorder treatment.

  11. HEADPLAY Personal Cinema System Facilitates Intravenous Cannulation in Children: A Randomized Controlled Trial.

    PubMed

    Lim, Evangeline; Fabila, Teddy; Sze Ying, Thong; Tan, Josephine

    2013-01-01

    HEADPLAY personal cinema system (PCS) is a portable visual headset/visor through which movie clips may be viewed. We studied the use of HEADPLAY PCS as a distraction tool in facilitating intravenous cannulation in children undergoing anaesthesia. 60 children were enrolled into the study and randomized into 2 groups. EMLA local anaesthetic cream was used to reduce the pain associated with intravenous cannulation. Children in group 1 wore the HEADPLAY visor whereas children in group 2 were subject to conventional distraction therapy. Children were asked to rate their anxiety, pain, and satisfaction scores after intravenous cannulation. Periprocedural anxiety was also determined using the modified Yale Preoperative Anxiety Scale (mYPAS). There were no statistically significant differences in terms of pain and anxiety scores between the 2 groups. Although the satisfaction score of the children in the HEADPLAY PCS group was marginally higher compared to the conventional group, this did not hit statistical significance. 86.6% of children in group 1 reported that they would want to use the visor again for their next intravenous cannulation. We conclude that HEADPLAY PCS is a distraction tool that is acceptable to most children and can contribute towards satisfaction of the intravenous cannulation process in children.

  12. HEADPLAY Personal Cinema System Facilitates Intravenous Cannulation in Children: A Randomized Controlled Trial

    PubMed Central

    Lim, Evangeline; Fabila, Teddy; Sze Ying, Thong; Tan, Josephine

    2013-01-01

    HEADPLAY personal cinema system (PCS) is a portable visual headset/visor through which movie clips may be viewed. We studied the use of HEADPLAY PCS as a distraction tool in facilitating intravenous cannulation in children undergoing anaesthesia. 60 children were enrolled into the study and randomized into 2 groups. EMLA local anaesthetic cream was used to reduce the pain associated with intravenous cannulation. Children in group 1 wore the HEADPLAY visor whereas children in group 2 were subject to conventional distraction therapy. Children were asked to rate their anxiety, pain, and satisfaction scores after intravenous cannulation. Periprocedural anxiety was also determined using the modified Yale Preoperative Anxiety Scale (mYPAS). There were no statistically significant differences in terms of pain and anxiety scores between the 2 groups. Although the satisfaction score of the children in the HEADPLAY PCS group was marginally higher compared to the conventional group, this did not hit statistical significance. 86.6% of children in group 1 reported that they would want to use the visor again for their next intravenous cannulation. We conclude that HEADPLAY PCS is a distraction tool that is acceptable to most children and can contribute towards satisfaction of the intravenous cannulation process in children. PMID:23840223

  13. A randomised controlled trial of perineural vs intravenous dexamethasone for foot surgery.

    PubMed

    Dawson, R L; McLeod, D H; Koerber, J P; Plummer, J L; Dracopoulos, G C

    2016-03-01

    We used 20 ml ropivacaine 0.75% for ankle blocks before foot surgery in 90 participants who we allocated in equal numbers to: perineural dexamethasone 8 mg and intravenous saline 0.9%; perineural saline 0.9% and intravenous dexamethasone 8 mg; or perineural and intravenous saline 0.9%. Dexamethasone increased the median (IQR [range]) time for the return of some sensation or movement, from 14.6 (10.8-18.8 [5.5-38.0]) h with saline to 24.1 (19.3-29.3 [5.0-44.0]) h when given perineurally, p = 0.00098, and to 20.9 (18.3-27.8 [8.8-31.3]) h when given intravenously, p = 0.0067. Dexamethasone increased the median (IQR [range]) time for the return of normal neurology, from 17.6 (14.0-21.0 [9.5-40.5]) h with saline to 27.5 (22.0-36.3 [7.0-53.0]) h when given perineurally, p = 0.00016, and to 24.0 (20.5-32.3 [13.0-42.5]) h when given intravenously, p = 0.0022. Dexamethasone did not affect the rates of block success, postoperative pain scores, analgesic use, or nausea and vomiting. The route of dexamethasone administration did not alter its effects.

  14. Toxicity, biodistribution, and ex vivo MRI detection of intravenously injected cationized ferritin.

    PubMed

    Beeman, Scott C; Georges, Joseph F; Bennett, Kevin M

    2013-03-01

    The goal of the work was to establish the toxicity and biodistribution of the superparamagnetic protein cationized ferritin (CF) after intravenous injection. Intravenously injected CF has been used to target the extracellular matrix with high specificity in the kidney glomerulus, allowing measurements of individual glomeruli using T2*-weighted MRI. For the routine use of CF as an extracellular matrix-specific tracer, it is important to determine whether CF is toxic. In this work, we investigated the renal and hepatic toxicity, leukocyte count, and clearance of intravenously injected CF. Furthermore, we studied CF labeling in several organs using MRI and immunohistochemistry. Serum measurements of biomarkers suggest that intravenous injection of CF is neither nephrotoxic nor hepatotoxic and does not increase leukocyte counts in healthy rats at a dose of 5.75 mg/100 g. In addition to known glomerular labeling, confocal and MRI suggest that intravenously injected CF labels the extracellular matrix of the hepatic sinusoid, extracellular glycocalyx of alveolar endothelial cells, and macrophages in the spleen. Liver T2* values suggest that CF is cleared by 7 days after injection. These results suggest that CF may serve as a useful contrast agent for detection of a number of structures and functions with minimal toxicity.

  15. Update on intravenous dipyridamole cardiac imaging in the assessment of ischemic heart disease

    SciTech Connect

    Younis, L.T.; Chaitman, B.R. )

    1990-01-01

    Intravenous dipyridamole is a relative selective coronary vasodilator which, when combined with thallium-201, provides a useful technique to assess myocardial perfusion. The intravenous dipyridamole is administered as an infusion at a rate of 0.14 mg/kg/min for 4 minutes. In the presence of significant coronary artery disease the increase of coronary blood flow is disproportionate between vessels with and without significant coronary lesions, providing the basis for detecting regional differences in flow using thallium-201. The test can be used alone or combined with low level exercise to increase test sensitivity. The test is safe when performed under medical supervision and when patient selection is done appropriately. Most of the side effects induced by dipyridamole infusion are well tolerated by patients and readily reversed with intravenous aminophylline and sublingual nitroglycerin. The average sensitivity and specificity of the dipyridamole thallium scintigraphy test from the major studies are 76% and 70%, respectively. The test is very useful in providing prognostic information in patients who are unable to exercise. A reversible thallium defect after dipyridamole infusion has been shown to be associated with significant mortality and morbidity in patients with documented or suspected coronary artery disease. The use of intravenous dipyridamole has been extended into other modalities of imaging, including 2-dimensional and Doppler echocardiography, to study functional changes in the left ventricular induced by the infusion of intravenous dipyridamole. 52 references.

  16. Two years of experience in the treatment of status epilepticus with intravenous levetiracetam.

    PubMed

    Eue, S; Grumbt, M; Müller, M; Schulze, A

    2009-08-01

    Since its introduction in 2006, 43 patients with various forms of status epilepticus (SE) have been treated with the intravenous formulation of levetiracetam (LEV) in our clinic. After ineffective treatment with benzodiazepines, intravenous LEV was administered as a short infusion (nonconvulsive and subtle SE) at a dose of 1000 or 2000 mg. In cases of convulsive SE, a fractionated injection of 1000 or 2000 mg was used. When the results for both are combined, SE could be terminated in 19 of 43 patients. Intravenous LEV was more effective in simple focal SE (3/5), complex focal SE (11/18) and myoclonic status (2/2) than in nonconvulsive (2/8) and subtle (1/2) SE. In no case was (secondarily) generalized convulsive status epilepticus (0/8) terminated. Intravenous LEV was also well-tolerated when injected in fractionated form. No severe adverse reactions were observed. As a result of this investigation, intravenous LEV in moderate doses may represent an efficacious and well-tolerated alternative for the treatment of focal (simple and complex focal) and myoclonic SE. Further investigations are needed to confirm this assumption as the patient numbers are quite low.

  17. Haemodynamics and plasma concentrations following sublingual GTN and intravenous, or inhaled, isosorbide dinitrate.

    PubMed Central

    Culling, W; Singh, H; Bashir, A; Griffiths, B E; Dalal, J J; Sheridan, D J

    1984-01-01

    We measured plasma nitrate levels and haemodynamics following sublingual glyceryl trinitrate (GTN) (0.5 mg), or isosorbide dinitrate (ISDN) administered intravenously (0.5 mg) or by inhalation (1.25 mg) in 23 patients undergoing cardiac catheterisation for investigation of chest pain. Peak levels were detected at 90 s and 5 min following intravenous and inhaled ISDN respectively and at 3 min following sublingual GTN. Intravenous and inhaled ISDN produced similar plasma levels at 30 s and both were significantly greater than following sublingual GTN. Plasma levels were maintained for longer following inhaled ISDN than intravenous ISDN or sublingual GTN. Haemodynamic responses were qualitatively similar following each treatment; reduction in pulmonary vascular resistance and pressure and left ventricular end diastolic pressure occurred in each group. Heart rate, cardiac output and LV dP/dt.P-1 remained unchanged. Maximal haemodynamic responses were greater following ISDN than GTN, with little difference between the two preparations of ISDN. Haemodynamic responses were more sustained following inhaled ISDN than following sublingual GTN or intravenous ISDN, the latter two being similar in this respect. These findings suggest that inhaled ISDN may provide more rapid and sustained relief from angina than sublingual GTN. PMID:6422972

  18. [Effect of intravenous treatment with OK-432 on the bone marrow in patients with lung cancer].

    PubMed

    Fujii, M; Ishikawa, M; Toki, H

    1984-03-01

    We studied effects of OK-432 on the bone marrow and peripheral blood cells of lung cancer patients. The nuclear cell count of bone marrow increased in 5 to 7 patients upon intravenous treatment with OK-432 compared with 3 of 6 patients who were intramuscularly treated with OK-432. Serial neutrophil counts of bone marrow increased in all 7 patients treated intravenously compared with 3 of 6 patients treated intramuscularly. The mean nuclear cell count or the serial neutrophil count of bone marrow in intravenously treated patients was significantly higher than the pretreatment values (p less than 0.001). In the peripheral blood picture, the difference in white blood cells or neutrophils before and after intravenous treatment was also statistically significant (p less than 0.01). There was no change in the erythrocytic series count of bone marrow and the hemoglobin count. Our results support the superiority of intravenous OK-432 treatment over intramuscular treatment in the growth-accelerating effect on bone marrow cells, especially regarding the neutrophil series.

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

    SciTech Connect

    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

    2015-08-15

    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.

  20. Impact of Intervention by an Antimicrobial Stewardship Team on Conversion from Intravenous to Oral Fluoroquinolones

    PubMed Central

    Jeong, Young Mi; Lee, Jung Hwa; Lee, Eunsook

    2017-01-01

    Background Early conversion from intravenous to oral antibiotics plays an important role in lowering the risk of catheter-associated infections, reducing the workload of nurses, decreasing direct and indirect costs, and shortening hospital stays. In August 2015, an antimicrobial stewardship program (ASP) was implemented to facilitate conversion from intravenous to oral administration of fluoroquinolones in our institute. This study evaluated the clinical and economic impact of the intervention. Materials and Methods Data were retrospectively collected by reviewing electronic medical records. All hospitalized patients aged 18 and older who met the study inclusion criteria for the conversion were included between August and November 2015. We computed the physicians' adherence rate to the ASP recommendations. We also measured the total use of fluoroquinolones, length of hospital stay, and medication costs. Results During 4 months, 129 cases were enrolled in the study. The adherence rate was 79.8%. The average total prescription volume of intravenous fluoroquinolones, the length of hospital stay, and the total cost of the fluoroquinolones statistically significantly decreased in the intervention-adherent group. Conclusion Intervention to facilitate conversion from intravenous to oral administration has reduced excess use of intravenous fluoroquinolones and length of hospital stay. With these findings, further implementations of the ASP extending to other antibiotics may be warranted. PMID:28332344

  1. Pharmacokinetics of Hydromorphone after Intravenous and Intramuscular Administration in Male Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Kelly, Kristi R; Pypendop, Bruno H; Christe, Kari L

    2014-01-01

    This study reports the pharmacokinetics of hydromorphone after intravenous and intramuscular administration to rhesus macaques (Macaca mulatta ). Hydromorphone (0.075 mg/kg) was administered intravenously as a bolus or intramuscularly on separate occasions to healthy, socially housed, socially reared, adult, intact male rhesus macaques (n = 4). Blood samples were collected prior to and until 10 h after administration. Serum hydromorphone concentrations were analyzed with liquid chromatography-mass spectrometry. Compartment models were fit to time–concentration data. A 3-compartment model with input in and elimination from the central compartment best fit intravenous data, whereas a 1-comparment model best fit intramuscular data. After intravenous administration, the median clearance and terminal half-life were 37.7 (range, 33.7 to 47.1) mL/kg/min and 142 (range, 131 to 218) min, respectively. The median (range) elimination half-life after intramuscular administration was 81.5 (77.2 to 92.5) min. Median intramuscular bioavailability was 92% (range, 75% to 104%). Rhesus macaques maintained concentrations greater than or equal to 4.0 ng/mL for at least 2 h after intravenous and intramuscular administration. The disposition of hydromorphone was characterized by a large volume of distribution and moderate clearance. Intramuscular administration resulted in rapid and almost complete drug absorption. Whole-body pruritus, sedation, and decreased appetite were observed in all macaques after initial drug administration. PMID:25255074

  2. [Iron substitution in outpatients in Switzerland: Increase of costs associated with intravenous administration].

    PubMed

    Giger, Max; Achermann, Rita

    2013-01-01

    Iron anaemia and iron-deficient erythropoiesis are treated with oral iron supplements. For chronic haemodialysis or in the case of therapy failure or intolerance to oral iron therapy, intravenous supplements are administered. The costs of iron supplements borne by statutory health care insurance had strongly increased during the observation period from 2006 to 2010. Based on the invoice data of a large health insurance company with a market share of around 18 %, prescription data of iron preparations and laboratory tests were analysed and extrapolated to the Swiss population. During the 5-year observation period, costs of intravenous iron substitution increased by 16.5 m EUR (340.3 %) and the number of individuals treated by 243.5 %. A sharp rise was observed in women of menstruating age, which was mainly due to prescriptions issued by primary care physicians. More than 8 % of intravenous iron substitutions were administered without prior laboratory analysis,and must therefore be regarded as off-label use. A cost-benefit analysis is needed to demonstrate the additional value of intravenous over oral iron supplementation, and intravenous iron supplementation should be administered only to patients with proven iron deficiency.

  3. A pilot study assessing pharmacokinetics and tolerability of oral and intravenous baclofen in healthy adult volunteers.

    PubMed

    Agarwal, Suresh K; Kriel, Robert L; Cloyd, James C; Coles, Lisa D; Scherkenbach, Lisa A; Tobin, Michael H; Krach, Linda E

    2015-01-01

    Our objective was to characterize baclofen pharmacokinetics and safety given orally and intravenously. Twelve healthy subjects were enrolled in a randomized, open-label, crossover study and received single doses of baclofen: 3 or 5 mg given intravenously and 5 or 10 mg taken orally with a 48-hour washout. Blood samples for baclofen analysis were collected pre-dose and at regular intervals up to 24 hours post-dose. Clinical response was assessed by sedation scores, ataxia, and nystagmus. Mean absolute bioavailability of oral baclofen was 74%. Dose-adjusted areas under the curve between the oral and intravenous arms were statistically different (P = .0024), whereas area under the curve variability was similar (coefficient of variation: 18%-24%). Adverse effects were mild in severity and not related to either dose or route of administration. Three- and 5-mg intravenous doses of baclofen were well tolerated. Seventy-four percent oral bioavailability indicates that smaller doses of intravenous baclofen are needed to attain comparable total drug exposures.

  4. Human immunoglobulin 10 % with recombinant human hyaluronidase: replacement therapy in patients with primary immunodeficiency disorders.

    PubMed

    Sanford, Mark

    2014-08-01

    Human immunoglobulin is an established replacement therapy for patients with primary immunodeficiency disorders (PIDs). Recombinant human hyaluronidase (rHuPH20) is a spreading factor that temporarily digests hyaluronan in the skin interstitium enabling large volumes of fluid or drug solutions to be infused and absorbed subcutaneously. HyQvia® (IGHy) is a new combination product whereby rHuPH20 is injected subcutaneously, followed by human immunoglobulin 10 % infused through the same needle. Thus, IGHy can be administered at a reduced frequency compared with non-facilitated subcutaneous injection of human immunoglobulin, and with a lower frequency of infusion reactions than with intravenous administration. Home-based administration of IGHy is also feasible for adequately trained patients. IGHy was compared with intravenous human immunoglobulin 10 % in a non-randomized, open-label, phase 3 study in patients aged ≥2 years with PIDs who were receiving human immunoglobulin replacement therapy (n = 87). In this study, trough IgG concentrations, acute serious bacterial infection rates (primary endpoint) and occurrences of adverse events during the IGHy treatment period were generally similar to those observed during an intravenous treatment period. IGHy was associated with a numerically lower rate of systemic adverse events and a numerically higher rate of localized adverse events than those observed with intravenous treatment. Compared with intravenous administration, IGHy was administered at a significantly higher maximum flow rate and at a similar frequency. Most patients preferred IGHy over intravenous administration. IGHy offers a new method for subcutaneous delivery of human immunoglobulin replacement therapy in patients with PIDs.

  5. Is intravenous cholangiography an alternative to the routine per-operative cholangiogram?

    PubMed Central

    Huddy, S. P.; Southam, J. A.

    1989-01-01

    Ultrasonography, although an accurate method of detecting stones within the gall bladder, is unreliable for the detection of bile duct stones for which per-operative cholangiography remains the standard investigation. Fifty seven patients undergoing elective cholecystectomy had both a pre-operative intravenous cholangiogram and per-operative cholangiography. The pre-operative investigation is shown to be at least as effective in the detection of common bile duct stones and only missed a duct stone in one patient. The substitution of pre-operative intravenous cholangiography for routine per-operative cholangiography would result in a significant reduction in operating time, may provide advance knowledge on the biliary anatomy and would allow advance planning of the likely procedure. It is suggested that pre-operative intravenous cholangiography, carried out on the day of admission, should be considered as a preferred alternative investigation to per-operative cholangiography. PMID:2694145

  6. [Is intravenous immunoglobulin effective in toxic epidermal necrolysis and Stevens-Johnson syndrome?].

    PubMed

    Navajas, Lucas; Rada, Gabriel

    2014-10-17

    Toxic epidermal necrolysis and Stevens-Johnson syndrome are severe cutaneous adverse drug reactions. Intravenous immunoglobulin is described as a therapeutic option, however its use is still controversial. Using Epistemonikos database, which is maintained by screening over 20 databases, we identified six systematic reviews, including 39 primary studies. We combined the evidence using tables for summary of findings, following the GRADE approach, and concluded there is uncertainty about the effects of intravenous immunoglobulin because the certainty of the evidence is very low; it probably leads to important adverse effects; and has high cost. Intravenous immunoglobulin should not be used outside the context of a clinical trial, or only in cases where other treatments have failed and there are no resource constraints.

  7. Hemolytic Disease of the Fetus and Newborn due to Intravenous Drug Use

    PubMed Central

    Markham, Kara B.; Scrape, Scott R.; Prasad, Mona; Rossi, Karen Q.; O'Shaughnessy, Richard W.

    2016-01-01

    Objectives The objective is to present a pregnancy complication associated with intravenous drug use, namely, that of red blood cell alloimmunization and hemolytic disease of the fetus and newborn. Methods An observational case series is presented including women with red blood cell alloimmunization most likely secondary to intravenous drug abuse Results Five pregnancies were identified that were complicated by red blood cell alloimmunization and significant hemolytic disease of the fetus and newborn, necessitating intrauterine transfusion, an indicated preterm birth, or neonatal therapy. Conclusions As opioid abuse continues to increase in the United States, clinicians should be aware of the potential for alloimmunization to red blood cell antibodies as yet another negative outcome from intravenous drug abuse. PMID:26989567

  8. Leaching of diethylhexyl phthalate from polyvinyl chloride bags into intravenous cyclosporine solution

    SciTech Connect

    Venkataramanan, R.; Burckart, G.J.; Ptachcinski, R.J.; Blaha, R.; Logue, L.W.; Bahnson, A.; Giam, C.S.; Brady, J.E.

    1986-11-01

    The release of diethylhexyl phthalate (DEHP) from flexible polyvinyl chloride containers into intravenous cyclosporine solutions was studied. Intravenous cyclosporine solution or solutions containing the vehicle Cremophor EL and alcohol in dextrose were prepared in an all-glass system and stored in polyvinyl chloride (PVC) bags. Four samples were obtained at different time intervals, and DEHP content was analyzed by gas chromatography. The amount of DEHP that was leached into solutions stored in the PVC bags increased as storage time increased. By 48 hours, nearly 33 mg of DEHP had leached into the solution. Intravenous cyclosporine solutions should be prepared in glass containers to minimize patient exposure to DEHP. If plastic bags are used for preparing cyclosporine injections, the injections must be used immediately after preparation.

  9. Treatment of a mild chronic case of ciguatera fish poisoning with intravenous mannitol, a case study.

    PubMed

    Mitchell, Gary

    2005-03-01

    This article describes a recent case of ciguatera poisoning treated with intravenous mannitol. Mannitol has been used with good effect in non-controlled studies in acutely severely poisoned patients, but is not described in the treatment of chronic or milder poisoning. Our patient was a 35-year-old Niuean man who had eaten a ciguatoxic fish two weeks previously. His symptoms were not severe but were very unpleasant and restricted his ability to work. He was given a single dose of mannitol (0.66g/kg) as an intravenous infusion over two hours. His symptoms dramatically improved within 24 hours, and within a few days he felt virtually back to his former self. He experienced no side effects to the mannitol. It is suggested that intravenous mannitol may prove to be a useful treatment for mild to moderate ciguatera poisoning, and for patients who present late for treatment.

  10. Pulmonary intravascular talcosis mimicking miliary tuberculosis in an intravenous drug addict

    PubMed Central

    Altraja, Alan; Jürgenson, Katre; Roosipuu, Retlav; Laisaar, Tanel

    2014-01-01

    Pulmonary foreign body granulomatosis following intravenous administration of medications meant for oral use among drug addicts has been occasionally reported. This condition is often misdiagnosed because of its rarity, but rather due to its similarity to other pulmonary diseases that are more common. Here we report a case of pulmonary intravascular talcosis mimicking miliary tuberculosis in a young male intravenous drug addict from North-Eastern Estonia, known as a hotspot for tuberculosis and drug misuse. The condition was caused by intravenous administration of crushed tablets of diphenhydramine, but miliary tuberculosis was misdiagnosed on patient's demographical, clinical and radiological grounds and a decision to start treatment with four first-line antituberculosis drugs followed. The current report refers to the importance of considering rare causes of pulmonary disseminations with attempts to identify the causative agent and warns against the use of antituberculosis treatment without confirmation of microbiological diagnosis of tuberculosis. PMID:24713715

  11. Intravascular Talcosis due to Intravenous Drug Use Is an Underrecognized Cause of Pulmonary Hypertension

    PubMed Central

    Griffith, Christopher C.; Raval, Jay S.; Nichols, Larry

    2012-01-01

    Intravenous injection of illegal drugs or medications meant for oral administration can cause granulomatous disease of the lung. This intravascular talcosis results in pulmonary fibrosis and pulmonary hypertension. Nine cases of histologically confirmed intravascular talcosis were reviewed with specific attention given to the clinical histories in these patients. Five autopsy cases were included in this series with detailed investigation in the anatomic features associated with intravascular talcosis and pulmonary hypertension. All nine patients showed perivascular and/or intravascular deposition of polarizable foreign material in their lungs. Intravascular talcosis as a result of previous intravenous drug use was not clinically suspected in any patient despite clinically diagnosed pulmonary hypertension in five. All patients showed dilatation of the right and left heart, but none had dilatation of the aortic valve. Congestive heart failure with hepatosplenomegaly was also common. We conclude that intravascular talcosis is an underdiagnosed cause of pulmonary hypertension in patients with known history of intravenous drug use. PMID:22645680

  12. Pulmonary intravascular talcosis mimicking miliary tuberculosis in an intravenous drug addict.

    PubMed

    Altraja, Alan; Jürgenson, Katre; Roosipuu, Retlav; Laisaar, Tanel

    2014-04-08

    Pulmonary foreign body granulomatosis following intravenous administration of medications meant for oral use among drug addicts has been occasionally reported. This condition is often misdiagnosed because of its rarity, but rather due to its similarity to other pulmonary diseases that are more common. Here we report a case of pulmonary intravascular talcosis mimicking miliary tuberculosis in a young male intravenous drug addict from North-Eastern Estonia, known as a hotspot for tuberculosis and drug misuse. The condition was caused by intravenous administration of crushed tablets of diphenhydramine, but miliary tuberculosis was misdiagnosed on patient's demographical, clinical and radiological grounds and a decision to start treatment with four first-line antituberculosis drugs followed. The current report refers to the importance of considering rare causes of pulmonary disseminations with attempts to identify the causative agent and warns against the use of antituberculosis treatment without confirmation of microbiological diagnosis of tuberculosis.

  13. Intravascular Talcosis due to Intravenous Drug Use Is an Underrecognized Cause of Pulmonary Hypertension.

    PubMed

    Griffith, Christopher C; Raval, Jay S; Nichols, Larry

    2012-01-01

    Intravenous injection of illegal drugs or medications meant for oral administration can cause granulomatous disease of the lung. This intravascular talcosis results in pulmonary fibrosis and pulmonary hypertension. Nine cases of histologically confirmed intravascular talcosis were reviewed with specific attention given to the clinical histories in these patients. Five autopsy cases were included in this series with detailed investigation in the anatomic features associated with intravascular talcosis and pulmonary hypertension. All nine patients showed perivascular and/or intravascular deposition of polarizable foreign material in their lungs. Intravascular talcosis as a result of previous intravenous drug use was not clinically suspected in any patient despite clinically diagnosed pulmonary hypertension in five. All patients showed dilatation of the right and left heart, but none had dilatation of the aortic valve. Congestive heart failure with hepatosplenomegaly was also common. We conclude that intravascular talcosis is an underdiagnosed cause of pulmonary hypertension in patients with known history of intravenous drug use.

  14. Spontaneous kyphotic collapse followed by autostabilisation secondary to cervical osteomyelitis in an intravenous drug abuser.

    PubMed

    Arun, Ranganathan; Kasbekar, Anand Vijay; Mehdian, S M Hossein

    2007-12-01

    There is a high risk of cervical osteomyelitis in intravenous drug abusers due to the use of jugular veins for administration of drugs. Here described is a case of rapid vertebral body destruction at two levels leading to a progressive kyphotic deformity followed by autofusion, secondary to cervical osteomyelitis. The case report goes on to hypothesise about the unique manner of progression of untreated cervical osteomyelitis with a rapid onset of kyphotic deformity and associated severe bone destruction in an intravenous drug abuser. Due to the high incidence of osteomyelitis in intravenous drug abusers, there should be a low threshold to investigate for this condition and early magnetic resonance imaging is vital. It alerts the treating spine surgeon to the fact that early immobilisation is crucial in these cases to prevent a severe impending deformity that can be surgically challenging.

  15. Intravenous Heroin-Associated Delayed Spongiform Leukoencephalopathy: Case Report and Reviews of the Literature.

    PubMed

    Pirompanich, Pattarin; Chankrachang, Siwaporn

    2015-07-01

    Heroin-associated spongiform leukoencephalopathy is a rare, and sometimes fatal, condition usually caused by vapor inhalation of heroin. The authors report a 41-year-old man who was diagnosed with delayed spongiform leukoencephalopathy three weeks after injecting heroin intravenously. He had been admitted to another hospital due to acute heroin overdose, which had occurred four hours after intravenous injection of an unknown amount of heroin. His clinical condition showed progressive improvement and he was discharged 12 days after admission. Three weeks after this episode, his cognitive functioning declined. Akinetic mutism, spasticity and hyperreflexia of all extremities were observed. Electroencephalography (EEG) and imaging of the brain showed typical characteristics of spongiform leukoencephalopathy. The three and six-month follow-up of the patient showed clinical improvement and this was corroborated through EEG measures and brain imaging. The discussion summarizes eight previously reported cases of intravenous heroin associated spongiform leukoencephalopathy and compares them to the authors'case.

  16. A Metabolomic Analysis of Two Intravenous Lipid Emulsions in a Murine Model

    PubMed Central

    Kalish, Brian T.; Le, Hau D.; Gura, Kathleen M.; Bistrian, Bruce R.; Puder, Mark

    2013-01-01

    Background Parenteral nutrition (PN), including intravenous lipid administration, is a life-saving therapy but can be complicated by cholestasis and liver disease. The administration of intravenous soy bean oil (SO) has been associated with the development of liver disease, while the administration of intravenous fish oil (FO) has been associated with the resolution of liver disease. The biochemical mechanism of this differential effect is unclear. This study compares SO and FO lipid emulsions in a murine model of hepatic steatosis, one of the first hits in PN-associated liver disease. Methods We established a murine model of hepatic steatosis in which liver injury is induced by orally feeding mice a PN solution. C57BL/6J mice were randomized to receive PN alone (a high carbohydrate diet (HCD)), PN plus intravenous FO (Omegaven®; Fresenius Kabi AG, Bad Homburg VDH, Germany), PN plus intravenous SO (Intralipid®; Fresenius Kabi AG, Bad Homburg v.d.H., Germany, for Baxter Healthcare, Deerfield, IL), or a chow diet. After 19 days, liver tissue was harvested from all animals and subjected to metabolomic profiling. Results The administration of an oral HCD without lipid induced profound hepatic steatosis. SO was associated with macro- and microvesicular hepatic steatosis, while FO largely prevented the development of steatosis. 321 detectable compounds were identified in the metabolomic analysis. HCD induced de novo fatty acid synthesis and oxidative stress. Both FO and SO relieved some of the metabolic shift towards de novo lipogenesis, but FO offered additional advantages in terms of lipid peroxidation and the generation of inflammatory precursors. Conclusions Improved lipid metabolism combined with reduced oxidative stress may explain the protective effect offered by intravenous FO in vivo. PMID:23565157

  17. Management of acute central retinal artery occlusion: Intravenous thrombolysis is feasible and safe.

    PubMed

    Préterre, Cécile; Godeneche, Gaelle; Vandamme, Xavier; Ronzière, Thomas; Lamy, Matthias; Breuilly, Christophe; Urbanczyk, Cédric; Wolff, Valérie; Lebranchu, Pierre; Sevin-Allouet, Mathieu; Guillon, Benoit

    2017-01-01

    Background Although acute central retinal artery occlusion is as a stroke in the carotid territory (retinal artery), its management remains controversial. The aim of this study was to assess the feasibility and safety of intravenous thrombolysis delivered within 6 h of central retinal artery occlusion in French stroke units. Methods We performed a retrospective analysis of patients treated with intravenous alteplase (recombinant tissue-plasminogen activator), based on stroke units thrombolysis registers from June 2005 to June 2015, and we selected those who had acute central retinal artery occlusion. The feasibility was assessed by the ratio of patients that had received intravenous alteplase within 6 h after central retinal artery occlusion onset among those who had been admitted to the same hospital for acute central retinal artery occlusion. All adverse events were documented. Results Thirty patients were included. Visual acuity before treatment was limited to "hand motion", or worse, in 90% of the cases. The mean onset-to-needle time was 273 min. The individuals treated with intravenous alteplase for central retinal artery occlusion represented 10.2% of all of the patients hospitalized for central retinal artery occlusion in 2013 and 2014. We observed one occurrence of major bleeding, a symptomatic intracerebral hemorrhage. Conclusion When applied early on, intravenous thrombolysis appears to be feasible and safe, provided that contraindications are given due consideration. Whether intravenous thrombolysis is more effective than conservative therapy remains to be determined. In order to conduct a well-designed prospective randomized control trial, an organized network should be in place.

  18. Pharmacokinetics and Bioavailability of a Therapeutic Enzyme (Idursulfase) in Cynomolgus Monkeys after Intrathecal and Intravenous Administration

    PubMed Central

    Xie, Hongsheng; Chung, Jou-Ku; Mascelli, Mary Ann; McCauley, Thomas G.

    2015-01-01

    Intravenous enzyme replacement therapy with iduronate-2-sulfatase is an approved treatment for Hunter syndrome, however, conventional intravenous delivery cannot treat the neurologic manifestations of the disease due to its limited central nervous system penetration. Intrathecal administration of iduronate-2-sulfatase for delivery to the central nervous system is currently under investigation. The objective of this study was to evaluate the pharmacokinetics of idursulfase in the central nervous system of cynomolgus monkeys (Macaca fasicularis) after intravenous and intrathecal administration. Twenty-seven monkeys, treatment-naïve to enzyme replacement therapy, were placed into 4 groups according to body weight: Group 1 was administered 0.5 mg/kg idursulfase intravenously, Groups 2–4 were administered an intrathecal formulation (1-, 10-, and 30-mg doses). Blood samples and cerebrospinal fluid (sampled at the cisterna magna or lumbar level) were collected at the same time points for 72 hours post dosing. Following intravenous administration, a high maximum serum concentration and rapid distribution of iduronate-2-sulfatase out of the central compartment were observed (elimination half-life: 4.3 hours). Iduronate-2-sulfatase exposure in the cerebrospinal fluid was limited, suggesting intravenous administration provided minimal penetration of the blood–brain barrier. Following intrathecal administration, a high maximum observed concentration was immediately noted and elimination half-life ranged between 7.8–10 hours and 5.9–6.7 hours (cisterna magna and lumbar sampling, respectively). Cerebrospinal fluid pharmacokinetic profiles at different doses of iduronate-2-sulfatase were similar and the dose/exposure relationship was proportional. After intrathecal administration, movement of iduronate-2-sulfatase from cerebrospinal fluid to serum was observed (systemic bioavailability was 40–83%). The clear penetration of iduronate-2-sulfatase into the cerebrospinal

  19. Understanding the causes of intravenous medication administration errors in hospitals: a qualitative critical incident study

    PubMed Central

    Keers, Richard N; Williams, Steven D; Cooke, Jonathan; Ashcroft, Darren M

    2015-01-01

    Objectives To investigate the underlying causes of intravenous medication administration errors (MAEs) in National Health Service (NHS) hospitals. Setting Two NHS teaching hospitals in the North West of England. Participants Twenty nurses working in a range of inpatient clinical environments were identified and recruited using purposive sampling at each study site. Primary outcome measures Semistructured interviews were conducted with nurse participants using the critical incident technique, where they were asked to discuss perceived causes of intravenous MAEs that they had been directly involved with. Transcribed interviews were analysed using the Framework approach and emerging themes were categorised according to Reason's model of accident causation. Results In total, 21 intravenous MAEs were discussed containing 23 individual active failures which included slips and lapses (n=11), mistakes (n=8) and deliberate violations of policy (n=4). Each active failure was associated with a range of error and violation provoking conditions. The working environment was implicated when nurses lacked healthcare team support and/or were exposed to a perceived increased workload during ward rounds, shift changes or emergencies. Nurses frequently reported that the quality of intravenous dose-checking activities was compromised due to high perceived workload and working relationships. Nurses described using approaches such as subconscious functioning and prioritising to manage their duties, which at times contributed to errors. Conclusions Complex interactions between active and latent failures can lead to intravenous MAEs in hospitals. Future interventions may need to be multimodal in design in order to mitigate these risks and reduce the burden of intravenous MAEs. PMID:25770226

  20. Use of intravenous iron supplementation in chronic kidney disease: an update.

    PubMed

    Macdougall, Iain C; Geisser, Peter

    2013-01-01

    Iron deficiency is an important clinical concern in chronic kidney disease (CKD), giving rise to iron-deficiency anemia and impaired cellular function. Oral supplementation, in particular with ferrous salts, is associated with a high rate of gastrointestinal side effects and is poorly absorbed, a problem that is avoided with intravenous iron. The most stable intravenous iron complexes (eg, iron dextran, ferric carboxymaltose, ferumoxytol, and iron isomaltoside 1000) can be given in higher single doses and more rapidly than less stable preparations (eg, sodium ferric gluconate). Iron complexes that contain dextran or dextran-derived ligands can cause dextran-induced anaphylactic reactions, which cannot occur with dextran-free preparations such as ferric carboxymaltose and iron sucrose. Test doses are advisable for conventional dextran-containing compounds. Iron supplementation is recommended for all CKD patients with anemia who receive erythropoiesis-stimulating agents, whether or not they require dialysis. Intravenous iron is the preferred route of administration in hemodialysis patients, with randomized trials showing a significantly greater increase in hemoglobin levels for intravenous versus oral iron and a low rate of treatment-related adverse events. In the nondialysis CKD population, the erythropoietic response is also significantly higher using intravenous versus oral iron, and tolerability is at least as good. Moreover, in some nondialysis patients intravenous iron supplementation can avoid, or at least delay, the need for erythropoiesis-stimulating agents. In conclusion, we now have the ability to achieve iron replenishment rapidly and conveniently in dialysis-dependent and nondialysis-dependent CKD patients without compromising safety.

  1. Intravenous thrombolysis in acute ischemic stroke patients with negative CT perfusion: a case series

    PubMed Central

    Mehra, Ratnesh; Qahwash, Omar; Richards, Boyd; Fessler, Richard D

    2014-01-01

    Background Computed tomography perfusion (CTP) is a commonly used modality of neurophysiologic imaging to aid the selection of acute ischemic stroke patients for neuroendovascular intervention by identifying the presence of penumbra versus infarcted brain tissue. However many patients present with evidence of cerebral ischemia with normal CTP, and in that case, should intravenous thrombolytics be given? Purpose To demonstrate if tissue-type plasminogen activator (tPA)-eligible stroke patients without perfusion defects demonstrated on CTP would benefit from administration of intravenous thrombolytics. Material and Methods We retrospectively identified patients presenting with acute ischemic symptoms who received intravenous tPA (IV-tPA) from January to June 2012 without a perfusion defect on CTP. Clinical and radiographic findings including the NIHSS at presentation, 24 h, and at discharge, symptomatic and asymptomatic hemorrhagic transformation, and the modified Rankin score at 30 days were collected. A reduction of NIHSS of greater than 4 points or resolution of symptoms was considered significant. Results Seventeen patients were identified with a mean NIHSS of 8.2 prior to administration of intravenous thrombolytics, 3.5 after 24 h, and 2.5 at discharge. Among them, 13 patients had significant improvement of NIHSS with a mean reduction of 6.15 points at 24 h. One patient initially improved but had delayed hemorrhagic transformation and died. Two patients had improvement in NIHSS but were not significant and two patients had increased in NIHSS at 24 h, although one eventually improved at discharge. There was no asymptomatic hemorrhagic transformation. Mean mRS at 3 months is 1.76. Conclusion The failure to identify a perfusion deficit by CTP should not be used as a contraindication for intravenous thrombolytics. Criteria for administration of intravenous thrombolytics should still be based on time from symptom onset as previously published by NINDS. PMID

  2. Effects of cysteine on the pharmacokinetics of intravenous clarithromycin in rats with protein-calorie malnutrition.

    PubMed

    Ahn, Choong Y; Kim, Eun J; Kwon, Jong W; Chung, Suk J; Kim, Sang G; Shim, Chang-K; Lee, Myung G

    2003-08-22

    Effects of cysteine on the pharmacokinetics of clarithromycin were investigated after intravenous administration of the drug at a dose of 20 mg/kg to control rats (4-week fed on 23% casein diet) and rats with PCM (protein-calorie malnutrition, 4-week fed on 5% casein diet) and PCMC (PCM treated with 250 mg/kg for oral cysteine twice daily during the fourth week). Clarithromycin has been reported to be metabolized via hepatic microsomal cytochrome P450 (CYP) 3A4 to 14-hydroxyclarithromycin (primary metabolite of clarithromycin) in human subjects. It has also been reported that in rats with PCM, CYP3A23 level decreased to 40-50% of control level, but decreased CYP3A23 level in rats with PCM completely returned to control level by oral cysteine supplementation (rats with PCMC). Human CYP3A4 and rat CYP3A23 proteins have 73% homology. In rats with PCM, the area under the plasma concentration-time curve from time zero to time infinity, AUC (567, 853 and 558 microg min/ml for control rats and rats with PCM and PCMC, respectively) and percentage of clarithromycin remaining after incubation with liver homogenate (69.6, 83.9 and 71.7%) were significantly greater than those in control rats and rats with PCMC. Moreover, in rats with PCM, the total body clearance, CL (35.3, 23.4 and 35.8 ml/min/kg), nonrenal clearance, CL(NR) (21.3, 15.2 and 24.1 ml/min/kg) and maximum velocity for the disappearance of clarithromycin after incubation with hepatic microsomal fraction, V(max) (351, 211 and 372 pmol/min/mg protein) were significantly slower than those in control rats and rats with PCMC. However, above mentioned each parameter was not significantly different between control rats and rats with PCMC. The above data suggested that metabolism of clarithromycin decreased significantly in rats with PCM as compared to control due to significantly decreased level of CYP3A23 in the rats. By cysteine supplementation (rats with PCMC), some pharmacokinetic parameters of clarithromycin (AUC

  3. Quarterly intravenous injection of ibandronate to treat osteoporosis in postmenopausal women.

    PubMed

    Sambrook, Philip

    2007-01-01

    Osteoporosis is a chronic condition that generally requires long-term therapy for fracture risk reduction to become apparent. Although the bisphosphonates have made a major contribution to how clinicians manage osteoporosis, compliance with therapy has generally been less in the real-world setting than seen in clinical trials. Less-frequently administered dosage regimens or nonoral routes may enhance compliance and so maximize the therapeutic benefit of bisphosphonates. Ibandronate is a nitrogen-containing bisphosphonate, whose high potency allows it to be administered orally or intravenously with extended dosing intervals. This paper will review the role of intravenous ibandronate in the treatment of postmenopausal osteoporosis.

  4. [Good response of scleromyxedema and dermato-neuro syndrome to treatment with intravenous immunoglobulins].

    PubMed

    Bielsa, I; Benvenutti, F; Guinovart, R M; Ferrándiz, C

    2012-05-01

    Scleromyxedema is a potentially serious disease that can have various systemic complications. One of the most frequent forms of central nervous system involvement is dermato-neuro syndrome. High-dose intravenous immunoglobulins are among the drug treatments that have been used for this syndrome. We describe 2 patients with scleromyxedema, one of whom developed dermato-neuro syndrome. Both patients responded well to treatment with high-dose intravenous immunoglobulins. We suggest this therapy as a suitable first-line treatment for scleromyxedema and for its neurological complications.

  5. Carotid Artery Stenting for Acute Ischemic Stroke Patients after Intravenous Recombinant Tissue Plasminogen Activator Treatment

    PubMed Central

    Deguchi, Ichiro; Hayashi, Takeshi; Neki, Hiroaki; Yamane, Fumitaka; Ishihara, Shoichiro; Tanahashi, Norio; Takao, Masaki

    2016-01-01

    We herein report three ischemic stroke patients who underwent emergency carotid artery stenting after receiving intravenous tissue plasminogen activator (t-PA) treatment. All patients received antiplatelet medications immediately before stent placement for loading as well as dual antiplatelet therapy after stenting. Under high-dose and dual antiplatelet therapy, none of the three patients showed symptomatic intracranial hemorrhaging. However, one case showed reocclusion of the placed stent after acute thrombosis. As a result, new treatment strategies for the use of antiplatelet agents during emergency stent placement must be developed, particularly for patients who have received intravenous t-PA therapy. PMID:27725550

  6. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury.

    PubMed

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-05-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 10(6) rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells.

  7. Acute respiratory distress following intravenous injection of an oil-steroid solution

    PubMed Central

    Russell, Michael; Storck, Aric; Ainslie, Martha

    2011-01-01

    A case of acute respiratory distress and hypoxemia following accidental intravenous injection of an oil-steroid solution in a body builder is presented. Chest roentography at the time of presentation showed diffuse bilateral opacities, and computed tomography revealed predominantly peripheral ground-glass opacifications. The patient’s symptoms gradually improved over 48 h and imaging of the chest was unremarkable one week later. The pathophysiology, diagnosis and treatment of this rare but potentially life-threatening complication of intravenous oil injection are discussed. PMID:22059184

  8. Use of a 24 gauge intravenous cannula for minimally invasive trabeculectomy.

    PubMed

    Dada, Tanuj; Angmo, Dewang; Temkar, Shreyas; Sharma, Reetika

    2015-01-01

    We describe an innovative technique for performing standardized low cost glaucoma filtration surgery using a polytetrafluoroethylene (PTFE) intravenous cannula. The trocar of a 24 gauge (24G) PTFE intravenous cannula was used to create a trabeculectomy ostium and its tube was inserted under a partial thickness scleral flap in 2 patients with advanced glaucomatous optic neuropathy, in whom intraocular pressure (IOP) was not controlled on maximal tolerable hypotensive therapy. Postoperatively, IOP of the operated eyes at 3, 6 and 9 months' follow-up ranged from 12 to 15 mmHg with a well formed anterior chamber and a diffuse bleb.

  9. Adult-onset opsoclonus-myoclonus syndrome due to West Nile Virus treated with intravenous immunoglobulin.

    PubMed

    Hébert, Julien; Armstrong, David; Daneman, Nick; Jain, Jennifer Deborah; Perry, James

    2017-02-01

    A 63-year-old female with no significant past medical history was presented with a 5-day history of progressive opsoclonus-myoclonus, headaches, and fevers. Her workup was significant only for positive West-Nile Virus serum serologies. She received a 2-day course of intravenous immunoglobulin (IvIG). At an 8-week follow up, she had a complete neurological remission. Adult-onset opsoclonus-myoclonus syndrome is a rare condition for which paraneoplastic and infectious causes have been attributed. To our knowledge, this is the first case reported of opsoclonus-myoclonus secondary to West-Nile Virus treated with intravenous immunoglobulin monotherapy.

  10. Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug.

    PubMed

    Shlomi, Dekel; Shitrit, David; Bendayan, Daniele; Sahar, Gidon; Shechtman, Yitshak; Kramer, Mordechai R

    2008-01-01

    Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-year-old woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin) tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.

  11. Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug

    PubMed Central

    Shlomi, Dekel; Shitrit, David; Bendayan, Daniele; Sahar, Gidon; Shechtman, Yitshak; Kramer, Mordechai R

    2008-01-01

    Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-year-old woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin) tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis. PMID:18686743

  12. The comparative safety of intravenous iron dextran, iron saccharate, and sodium ferric gluconate.

    PubMed

    Fishbane, S; Kowalski, E A

    2000-01-01

    Intravenous iron treatment is an important component of anemia therapy for patients on dialysis. Until recently iron dextran was the only parenteral form of iron available in the United States. This drug has been associated with occasional serious adverse reactions, including full-blown anaphylaxis. In 1999 the Food and Drug Administration approved a second form of iron for intravenous administration, sodium ferric gluconate in sucrose. It is expected that by the time of this publication, a third agent, iron saccharate will also be approved. In this review the comparative safety of these three agents is critically evaluated.

  13. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    PubMed Central

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells. PMID:25206912

  14. Spinal osteomyelitis due to Mycobacterium fortuitum in a former intravenous drug user.

    PubMed

    Longardner, Katie; Allen, Ahkeel; Ramgopal, Moti

    2013-07-10

    A 47-year-old woman with a history of intravenous drug use presented to the emergency department with a 6-month history of pain in her lumbar back and right buttock. She had stopped injecting drugs 1 year ago. Physical examination was unremarkable except for paraspinal and right sacroiliac joint tenderness. MRI confirmed discitis, osteomyelitis and abscess formation in the L5-S1 disc space. She underwent extensive vertebral surgery and debridement of the spinal abscess. Her surgical cultures grew Mycobacterium fortuitum, and she was treated with an appropriate combination of intravenous antimicrobial therapy.

  15. The pharmacokinetics of intravenous fenoldopam in healthy, awake cats.

    PubMed

    O'Neill, K E; Labato, M A; Court, M H

    2016-04-01

    Fenoldopam is a selective dopamine-1 receptor agonist that improves diuresis by increasing renal blood flow and perfusion and causing peripheral vasodilation. Fenoldopam has been shown to induce diuresis and be well-tolerated in healthy cats. It is used clinically in cats with oliguric kidney injury at doses extrapolated from human medicine and canine studies. The pharmacokinetics in healthy beagle dogs has been reported; however, pharmacokinetic data in cats are lacking. The goal of this study was to determine pharmacokinetic data for healthy, awake cats receiving an infusion of fenoldopam. Six healthy, awake, client-owned cats aged 2-6 years old received a 120-min constant rate infusion of fenoldopam at 0.8 μg/kg/min followed by a 20-min washout period. Ascorbate stabilized plasma samples were collected during and after the infusion for the measurement of fenoldopam concentration by HPLC with mass spectrometry detection. This study showed that the geometric mean of the volume of distribution, clearance, and half-life (198 mL/kg, 46 mL/kg/min, and 3.0 mins) is similar to pharmacokinetic parameters for humans. No adverse events were noted. Fenoldopam at a constant rate infusion of 0.8 μg/kg per min was well tolerated in healthy cats. Based on the results, further evaluation of fenoldopam in cats with kidney disease is recommended.

  16. Studies of embryotoxicity and the incidence of external malformations after continuous intravenous infusion of alpha-chaconine in pregnant rats.

    PubMed

    Hellenäs, K E; Cekan, E; Slanina, P; Bergman, K

    1992-05-01

    Embryotoxicity and effects on the incidence of external malformations of the major potato glycoalkaloid alpha-chaconine (alpha-cha) were studied in rats. Pregnant Sprague-Dawley rats (n = 17) were given a continuous intravenous infusion of alpha-cha via implanted osmotic minipumps (1.7 mg/kg/day), to maintain a stable blood concentration on days 6-13 of gestation. Control animals received physiological saline solution or were left untreated, respectively. Blood serum levels of alpha-cha were monitored at selected time intervals during the treatment using a specific HPLC method. The foetal body weights and the number of resorbed or dead foetuses per litter in the alpha-cha treated group were not significantly different from the control groups. No case of malformation was detected among 143 foetuses inspected in the treated group. The average maternal blood serum concentration of alpha-cha measured during the experiment was 340 ng/ml. This is more than 20 times the average peak serum level previously reported for human volunteers after intake of potatoes with a total glycoalkaloid content at the upper safe limit for acute adverse effects. The results support the view that potato glycoalkaloids, at levels normally found in potatoes, do not present a risk for teratogenicity in humans.

  17. Antithrombin alfa in hereditary antithrombin deficient patients: A phase 3 study of prophylactic intravenous administration in high risk situations.

    PubMed

    Tiede, Andreas; Tait, R Campbell; Shaffer, Don W; Baudo, Francesco; Boneu, Bernard; Dempfle, Carl Erik; Horellou, Marie Helene; Klamroth, Robert; Lazarchick, John; Mumford, Andrew D; Schulman, Sam; Shiach, Caroline; Bonfiglio, Laura J; Frieling, Johan T M; Conard, Jacqueline; von Depka, Mario

    2008-03-01

    During surgery and childbirth, patients with hereditary antithrombin (AT) deficiency are at high risk for thrombosis, and heparin prophylaxis may not be sufficiently efficacious. In these patients, exogenous AT may be used in association with heparin. A recombinant human AT (generic name: antithrombin alfa) has been developed. This multi-center study assessed the efficacy and safety of prophylactic intravenous administration of antithrombin alfa to hereditary AT deficient patients in high risk situations, including elective surgery, childbirth, or cesarean section. Antithrombin alfa was administered prior to and during the high risk period for restoration and maintenance of AT activity at 100% of normal. Heparin, low-molecular-weight heparin, and/or vitamin K antagonists were used according to standard of care. The primary efficacy endpoint was the incidence of acute deep vein thrombosis (DVT) from baseline up to day 30 post dosing as assessed by independent central review of duplex ultrasonograms and/or venograms. Safety was assessed based on adverse events (AEs) and laboratory evaluations. Five surgical and nine obstetrical hereditary AT deficiency patients received antithrombin alfa for a mean period of seven days. No clinically overt DVT occurred. Central review of ultrasonograms identified signs of acute DVT in two out of 13 evaluable patients. No antithrombin alfa-related AEs were reported. No patient developed anti-antithrombin alfa antibodies. In conclusion, this study suggests that antithrombin alfa is a safe and effective alternative to human plasma-derived AT for treating hereditary AT deficiency patients at high risk for thromboembolic events.

  18. Nanostructured lipid carriers of artemether-lumefantrine combination for intravenous therapy of cerebral malaria.

    PubMed

    Prabhu, Priyanka; Suryavanshi, Shital; Pathak, Sulabha; Patra, Aditya; Sharma, Shobhona; Patravale, Vandana

    2016-11-20

    Patients with cerebral malaria (CM) are unable to take oral medication due to impaired consciousness and vomiting thus necessitating parenteral therapy. Quinine, artemether, and artesunate which are currently used for parenteral malaria therapy have their own drawbacks. The World Health Organization (WHO) has now banned monotherapy and recommends artemisinin-based combination therapy for malaria treatment. However, presently there is no intravenous formulation available for combination therapy of malaria. Artemether-Lumefantrine (ARM-LFN) is a WHO approved combination for oral malaria therapy. However, the low aqueous solubility of ARM and LFN hinders their intravenous delivery. The objective of this study was to formulate ARM-LFN nanostructured lipid carriers (NLC) for intravenous therapy of CM. ARM-LFN NLC were prepared by microemulsion template technique and characterized for size, drug content, entrapment efficiency, drug release, crystallinity, morphology, amenability to autoclaving, compatibility with infusion fluids, stability, antimalarial efficacy in mice, and toxicity in rats. The ARM-LFN NLC showed sustained drug release, amenability to autoclaving, compatibility with infusion fluids, good stability, complete parasite clearance and reversal of CM symptoms with 100% survival in Plasmodium berghei-infected mice, and safety in rats. The biocompatible ARM-LFN NLC fabricated by an industrially feasible technique offer a promising solution for intravenous therapy of CM.

  19. [Medication errors with concentrated potassium intravenous solutions: Data of the literature, context and prevention].

    PubMed

    Charpiat, B; Magdinier, C; Leboucher, G; Aubrun, F

    2016-01-01

    Accidental direct intravenous injection of a concentrated solution of potassium often leads to patient death. In France, recommendations of healthcare agencies to prevent such accidents cover only preparation and intravenous infusion conditions. Accidents continue to occur in French hospitals. These facts demonstrate that these recommendations are insufficient and ineffective to prevent such deaths, especially those occurring during a catheter flushing. This article reviews the measures able to reduce the number of accidents. Countries which removed concentrated ampoules from ward stocks observed a decrease of the number of accidental deaths. This withdrawal, recommended by the World Health Organization, is now part of standards in studies aimed at determining the safety of care in hospitals. However, removal alone is insufficient to eliminate the risk. The combination with other measures should be considered. These measures are the provision of a combination of diluted intravenous ready to use solutions, the promotion of the oral route with tablets and oral solutions for potassium replenishment and to make available products with safeguards to prevent single shot intravenous injection. Studies aimed at determining the consequences on preventing concentrated potassium accidents of a widespread distribution of isotonic sodium chloride pre-filled ready-to-use syringes for catheter flushing should be performed.

  20. Pharmacokinetics of amoxicillin-clavulanic acid combination after intravenous and intramuscular administration to turkeys and chickens.

    PubMed

    Carceles, C M; Vicente, M S; Escudero, E

    1995-12-01

    The pharmacokinetic behaviour of amoxicillin/clavulanic acid (4:1) combination was studied after intravenous and intramuscular administration of single doses (25 mg/kg body weight) to 15 turkeys and 15 chickens. The objective was to determine whether there are differences between turkeys and chickens in the disposition kinetics of amoxicillin and clavulanic acid. The plasma concentrations-time data were analysed by compartmental pharmacokinetic and non-compartmental methods. The disposition curves for both drugs after intravenous administration were best described by a two-compartment open model in turkeys and chickens. The apparent volumes of distribution of amoxicillin and clavulanic acid were similar in the two species. The body clearances of amoxicillin and clavulanic acid in turkeys were significantly slower than in chickens. The elimination half-life of amoxicillin was similar in turkeys (1.12 +/-0.09 h) and chickens (1.03 +/-0.11 h) after intravenous administration, but that of clavulanic acid differed significantly (P<0.05) between turkeys (1.12 +/-0.03 h) and chickens (0.98 +/- 0.05 h). After intramuscular administration both drugs had a significantly longer half-life (P<0.05) in turkeys and chickens than that after the intravenous treatment. The bioavailability after the intramuscular injection was high and similar with both drugs, but higher values were obtained for chickens than turkeys.