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Sample records for mesylate indisulam inhaled

  1. Inhalants

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  2. Inhalants

    ... uses inhalants may be unable to learn new things or may have a hard time carrying on simple conversations. If the cerebral ... get drugs on the street, it is really hard to know what you get, Sometimes, ... put in, all sorts of things could happen. And other times, one might get ...

  3. LAM Pilot Study with Imatinib Mesylate (LAMP-1)

    2017-10-01

    AWARD NUMBER: W81XWH-14-1-0132 TITLE: LAM Pilot Study with Imatinib Mesylate (LAMP-1) PRINCIPAL INVESTIGATOR: Charlie Strange, MD...regarding imatinib mesylate (imatinib) in the treatment of Lymphangioleiomyomatosis ( LAM ) sufficient to power and design a phase 3 imatinib vs. placebo...clinical trial. The hypothesis is that imatinib will be equivalent to rapamycin in short term efficacy and safety. Currently, most LAM patients are

  4. Inhaled Steroids

    ... considerations when your dosage changes. What about side effects and inhaled steroids? The most common side effects with inhaled steroids ... inhaled steroid has much less potential for side effects than steroid pills or syrups. There have been concerns regarding ...

  5. Inhalant Abuse

    ... is when you pour the product into a bag, hold it over your mouth and nose, and inhale. How is inhalant abuse diagnosed? If you think your child is abusing inhalants, talk to them. Be honest and open. Tell them ...

  6. Evaluation of different substrates for inkjet printing of rasagiline mesylate

    Genina, Natalja; Janßen, Eva Maria; Breitenbach, Armin

    2013-01-01

    The main goal of the present study was to evaluate applicability of the different model substrates, namely orodispersible films (ODFs), porous copy paper sheets, and water impermeable transparency films (TFs) in preparation of the inkjet-printed drug-delivery systems. Rasagiline mesylate (RM...

  7. Safety pharmacology of sibutramine mesylate, an anti-obesity drug.

    Kim, Eun-Joo; Park, Eun-Kyung; Suh, Kwee-Hyun

    2005-03-01

    Sibutramine mesylate is a new anti-obesity drug. It is a crystalline salt of sibutramine developed to improve the solubility of sibutramine hydrochloride. Methanesulfonic acid was used as a salt-forming acid instead of hydrochloric acid, resulting in a greatly improved solubility of 1000 mg/mL in water. Sibutramine mesylate was administered orally to ICR mice, Sprague-Dawley rats, and beagle dogs at dose levels of 1.15, 3.45, and 11.50 mg/kg to measure its effects on the central nervous system (CNS), general behaviour, cardiovascular-respiratory system and the other organ systems. Following administration of sibutramine mesylate, spontaneous locomotor activity was significantly increased from 120 min to 24 hours at 3.45 mg/kg and from 30 min to 24 hours at 11.50 mg/kg. Furthermore, there were a decrease in hexobarbital-induced sleep time, an increase in respiratory rate at 120 min, increases in intestinal transport capacity and gastric pH at 11.50 mg/kg, and decreases in gastric volume and total acidity at 3.45 and 11.50 mg/kg. However sibutramine mesylate caused no effects on general behaviour, motor coordination, body temperature, analgesia, convulsion, blood pressure, heart rate, electrocardiogram, cardiac functions of the isolated rat heart, isolated smooth muscles and renal function. Based on the above results, it was concluded that sibutramine mesylate caused effects on the spontaneous locomotor activity, hexobarbital-induced sleep time, respiration, gastrointestinal transport, and gastric secretion at a dose level of 3.45 mg/kg or greater but caused no effects on other general pharmacological reactions.

  8. Pd-Catalyzed Cross-Coupling Reactions of Amides and Aryl Mesylates

    Dooleweerdt, Karin; Fors, Brett P.; Buchwald, Stephen L.

    2010-01-01

    A catalyst, based on a biarylphosphine ligand, for the Pd-catalyzed cross-coupling reactions of amides and aryl mesylates is described. This system allows an array of aryl and heteroaryl mesylates to be transformed into the corresponding N-arylamides in moderate to excellent yields. PMID:20420379

  9. Tirilazad mesylate protects stored erythrocytes against osmotic fragility.

    Epps, D E; Knechtel, T J; Bacznskyj, O; Decker, D; Guido, D M; Buxser, S E; Mathews, W R; Buffenbarger, S L; Lutzke, B S; McCall, J M

    1994-12-01

    The hypoosmotic lysis curve of freshly collected human erythrocytes is consistent with a single Gaussian error function with a mean of 46.5 +/- 0.25 mM NaCl and a standard deviation of 5.0 +/- 0.4 mM NaCl. After extended storage of RBCs under standard blood bank conditions the lysis curve conforms to the sum of two error functions instead of a possible shift in the mean and a broadening of a single error function. Thus, two distinct sub-populations with different fragilities are present instead of a single, broadly distributed population. One population is identical to the freshly collected erythrocytes, whereas the other population consists of osmotically fragile cells. The rate of generation of the new, osmotically fragile, population of cells was used to probe the hypothesis that lipid peroxidation is responsible for the induction of membrane fragility. If it is so, then the antioxidant, tirilazad mesylate (U-74,006f), should protect against this degradation of stored erythrocytes. We found that tirilazad mesylate, at 17 microM (1.5 mol% with respect to membrane lecithin), retards significantly the formation of the osmotically fragile RBCs. Concomitantly, the concentration of free hemoglobin which accumulates during storage is markedly reduced by the drug. Since the presence of the drug also decreases the amount of F2-isoprostanes formed during the storage period, an antioxidant mechanism must be operative. These results demonstrate that tirilazad mesylate significantly decreases the number of fragile erythrocytes formed during storage in the blood bank.

  10. Successful Treatment For Chronic Eosinophilic Leukemia (CEL With Imatinib Mesylate

    Rayane da Silva Souza

    2017-12-01

    Full Text Available We report a case of a patient with Chronic Eosinophilic Leukemia (CEL with mutation in alfa PDGFR gene exhibiting a satisfactory response to treatment with imatinib mesylate. A 25-year-old man presented in a hematology service with a persistent cough and hemogram alterations. His blood count showed a hemoglobin level of 12.5 g/dL and a white blood cell count of 94,030/mm3, eosinophils were 68% of all cells. Bone marrow aspiration and biopsy showed hypercellularity with marked eosinophilia (77% and erythroid differentiation series was hypocellular with normoblast maturation. The immunohistochemically of the bone biopsy was positive for myeloperoxidase and negative for CD34/CD99, consistent with CEL. Fluorescence in situ hybridization (FISH for the beta-fraction of platelet-derived growth factor (PDGFRβ and Philadelphia chromosome (Ph 1 were negative and the alfa PDGFR (Platelet-Derived Growth Factor was positive and showed heterozygosis in c.2531T>C on 18 Exon and homozygous in C.2562+1G>A at the region of the splicing site at the 18 intron. Treatment was initiated and maintained by administering 400mg/day imatinib mesylate. Laboratory findings returned to normal ranges, with clinical improvement and a hematological response observed after the second month of therapy. Currently, the patient’s blood count shows the white blood cell count (5,400 total leukocytes, eosinophils (8.6/mm3, hemoglobin (15.5 g/dl, hematocrit (45.4% and platelets (298,000/mm3 within normal ranges. The mutation search was negative in in peripheral blood one year after the initial treatment. Our work corroborates other studies on the efficacy of imatinib mesylate in the treatment of patients with CSF PDGFR alpha positive. We emphasize the importance of molecular studies, considering its relevance for the correct staging of the disease. Since CEL is a rare disease, it is important to define its etiology and anticipate its treatment, thus minimizing the damage induced by

  11. Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

    Reardon, David A; Egorin, Merrill J; Quinn, Jennifer A; Rich, Jeremy N; Rich, Jeremy N; Gururangan, Sridharan; Gururangan, Idharan; Vredenburgh, James J; Desjardins, Annick; Sathornsumetee, Sith; Provenzale, James M; Herndon, James E; Dowell, Jeannette M; Badruddoja, Michael A; McLendon, Roger E; Lagattuta, Theodore F; Kicielinski, Kimberly P; Dresemann, Gregor; Sampson, John H; Friedman, Allan H; Salvado, August J; Friedman, Henry S

    2005-12-20

    We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

  12. Phentolamine mesylate: It′s role as a reversal agent for unwarranted prolonged local analgesia

    Harpreet Singh Grover

    2015-01-01

    Full Text Available Administration of local anesthesia is an integral procedure prior to dental treatments to minimize the associated pain. It is learned that its effect stays more than the time required for the dental procedure to be completed. This prolonged soft tissue anesthesia (STA can be detrimental, inconvenient, and unnecessary. Phentolamine mesylate, a Food and Drug Administration-approved drug essentially serves the purpose of faster recovery from numbness at the site of local anesthesia. This article reviews the development of the drug phentolamine mesylate and its indication as a local anesthetic reversal agent. A literature search for phentolamine mesylate as a STA reversal agent was conducted in PubMed using the terms "dental local anesthesia reversal, phentolamine mesylate" up to March 2014. The search was limited to articles published in English. The search revealed 13 PubMed indexed articles stating the development and application of phentolamine mesylate. Phentolamine mesylate is an important step in the progress of developing patient care as well as an aid to the dental clinician.

  13. New use of an old drug: inhibition of breast cancer stem cells by benztropine mesylate.

    Cui, Jihong; Hollmén, Maija; Li, Lina; Chen, Yong; Proulx, Steven T; Reker, Daniel; Schneider, Gisbert; Detmar, Michael

    2017-01-03

    Cancer stem cells (CSCs) play major roles in cancer initiation, metastasis, recurrence and therapeutic resistance. Targeting CSCs represents a promising strategy for cancer treatment. The purpose of this study was to identify selective inhibitors of breast CSCs (BCSCs). We carried out a cell-based phenotypic screening with cell viability as a primary endpoint, using a collection of 2,546 FDA-approved drugs and drug-like molecules in spheres formed by malignant human breast gland-derived cells (HMLER-shEcad cells, representing BCSCs) and control immortalized non-tumorigenic human mammary cells (HMLE cells, representing normal stem cells). 19 compounds were identified from screening. The chemically related molecules benztropine mesylate and deptropine citrate were selected for further validation and both potently inhibited sphere formation and self-renewal of BCSCs in vitro. Benztropine mesylate treatment decreased cell subpopulations with high ALDH activity and with a CD44+/CD24- phenotype. In vivo, benztropine mesylate inhibited tumor-initiating potential in a 4T1 mouse model. Functional studies indicated that benztropine mesylate inhibits functions of CSCs via the acetylcholine receptors, dopamine transporters/receptors, and/or histamine receptors. In summary, our findings identify benztropine mesylate as an inhibitor of BCSCs in vitro and in vivo. This study also provides a screening platform for identification of additional anti-CSC agents.

  14. Imatinib mesylate--gold standards and silver linings.

    Peggs, K

    2004-09-01

    Imatinib mesylate represents the first of a new generation of molecularly targeted therapies engineered to disrupt signal transduction pathways. It is a tyrosine kinase inhibitor with relatively selective activity against the Abelson (ABL) proto-oncogene, platelet-derived growth factor receptor, and c-KIT receptor. Deregulated tyrosine kinase activity has been implicated as a central pathogenic event in a number of human malignancies, most notably chronic myeloid leukemia. In this myeloproliferative disorder the t(9;22) reciprocal translocation results in the generation of a novel fusion oncoprotein, BCR-ABL, with constitutive tyrosine kinase activity. Imatinib inhibits this activity, inducing remarkable rates of hematological and cytogenetic remission in excess of those seen with alternative medical therapies. Following a large phase III study comparing its efficacy with the combination of interferon alpha and low-dose cytarabine, it has emerged as the current gold standard therapy for patients with chronic-phase disease without a potential bone marrow donor and those considered unsuitable for bone marrow transplantation. Its integration into the management of those patients who might be considered for transplantation, which has historically been considered the only potentially curative approach, remains a major challenge. The increasing recognition and subsequent molecular characterization of resistance mechanisms has reinforced the need to exercise caution against deferring a proven curative therapy in favor of a treatment approach that is still investigational, with the spectre of increased numbers of patients progressing to sudden-onset blast crisis remaining the potential dark cloud in the silver lining for imatinib.

  15. Solution-mediated phase transformation of haloperidol mesylate in the presence of sodium lauryl sulfate.

    Greco, Kristyn; Bogner, Robin

    2011-09-01

    Forming a salt is a common way to increase the solubility of a poorly soluble compound. However, the solubility enhancement gained by salt formation may be lost due to solution-mediated phase transformation (SMPT) during dissolution. The SMPT of a salt can occur due to a supersaturated solution near the dissolving surface caused by pH or other solution conditions. In addition to changes in pH, surfactants are also known to affect SMPT. In this study, SMPT of a highly soluble salt, haloperidol mesylate, at pH 7 in the presence of a commonly used surfactant, sodium lauryl sulfate (SLS), was investigated. Dissolution experiments were performed using a flow-through dissolution apparatus with solutions containing various concentrations of SLS. Compacts of haloperidol mesylate were observed during dissolution in the flow-through apparatus using a stereomicroscope. Raman microscopy was used to characterize solids. The dissolution of haloperidol mesylate was significantly influenced by the addition of sodium lauryl sulfate. In conditions where SMPT was expected, the addition of SLS at low concentrations (0.1-0.2 mM) reduced the dissolution of haloperidol mesylate. In solutions containing concentrations of SLS above the critical micelle concentration (CMC) (10-15 mM), the dissolution of haloperidol mesylate increased compared to below the CMC. The solids recovered from solubility experiments of haloperidol mesylate indicated that haloperidol free base precipitated at all concentrations of SLS. Above 5 mM of SLS, Raman microscopy suggested a new form, perhaps the estolate salt. The addition of surfactant in solids that undergo solution-mediated phase transformation can add complexity to the dissolution profiles and conversion.

  16. Validated UV-Spectrophotometric Methods for Determination of Gemifloxacin Mesylate in Pharmaceutical Tablet Dosage Forms

    R. Rote Ambadas

    2010-01-01

    Full Text Available Two simple, economic and accurate UV spectrophotometric methods have been developed for determination of gemifloxacin mesylate in pharmaceutical tablet formulation. The first UV-spectrophotometric method depends upon the measurement of absorption at the wavelength 263.8 nm. In second area under curve method the wavelength range for detection was selected from 268.5-258.5 nm. Beer’s law was obeyed in the range of 2 to 12 μgmL-1 for both the methods. The proposed methods was validated statistically and applied successfully to determination of gemifloxacin mesylate in pharmaceutical formulation.

  17. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  18. Physico-chemical stability of eribulin mesylate containing concentrate and ready-to-administer solutions.

    Spindeldreier, Kirsten; Thiesen, Judith; Lipp, Hans-Peter; Krämer, Irene

    2014-06-01

    The aim of this study was to determine the stability of commercially available eribulin mesylate containing injection solution as well as diluted ready-to-administer solutions stored under refrigeration or at room temperature. Stability was studied by a novel developed stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay with ultraviolet detection (detection wavelength 200 nm). Triplicate test solutions of eribulin mesylate containing injection concentrate (0.5 mg/mL) and with 0.9% sodium chloride solution diluted ready-to-administer preparations (0.205 mg/mL eribulin mesylate in polypropylene (PP) syringes, 0.020 mg/mL eribulin mesylate in polypropylene/polyethylene (PE) bags) were stored protected from light either at room temperature (25) or under refrigeration (2-8). Samples were withdrawn on day 0 (initial), 1, 3, 5, 7, 14, 21 and 28 of storage and assayed. Physical stability was determined by measuring the pH value once a week and checking for visible precipitations or colour changes. The stability tests revealed that concentrations of eribulin mesylate remained unchanged over a period of 28 days irrespective of concentration, container material or storage temperature. Neither colour changes nor visible particles have been observed. The pH value varied slightly over time but remained in the stability favourable range of 5-9. Eribulin mesylate injection (0.5 mg/mL) is physico-chemically stable over a period of 28 days after first puncture of the vial. After dilution with 0.9% NaCl vehicle solution, ready-to-administer eribulin mesylate injection solutions (0.205 mg/mL in PP syringe) and infusion solutions (0.02 mg/mL in prefilled PP/PE bags) are physico-chemically stable for a period of at least four weeks either refrigerated or stored at room temperature. For microbiological reasons storage under refrigeration is recommended.

  19. Inhalation Therapy in Horses.

    Cha, Mandy L; Costa, Lais R R

    2017-04-01

    This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobials. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Ciclesonide Oral Inhalation

    ... use ciclesonide inhalation.Ciclesonide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use ciclesonide ...

  1. Flunisolide Oral Inhalation

    ... use flunisolide inhalation.Flunisolide inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Do not use flunisolide ...

  2. Imatinib mesylate induces responses in patients with liver metastases from gastrointestinal stromal tumor failing intra-arterial hepatic chemotherapy

    Fiorentini Giammaria

    2006-01-01

    Full Text Available Background: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST, due to the typically hypervascular pattern of the tumor. Aims: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. Materials and Methods: Three patients (pts with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. Results: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. Conclusion: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

  3. Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate

    Seo JH

    2015-07-01

    Full Text Available Jae Hong Seo, Jung Bae Park, Woong-Kee Choi, Sunhwa Park, Yun Jin Sung, Euichaul Oh, Soo Kyung Bae College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, South Korea Objective: Cilostazol is a Biopharmaceutical Classification System class II drug with low solubility and high permeability, so its oral absorption is variable and incomplete. The aim of this study was to prepare two sulfonate salts of cilostazol to increase the dissolution and hence the oral bioavailability of cilostazol.Methods: Cilostazol mesylate and cilostazol besylate were synthesized from cilostazol by acid addition reaction with methane sulfonic acid and benzene sulfonic acid, respectively. The salt preparations were characterized by nuclear magnetic resonance spectroscopy. The water contents, hygroscopicity, stress stability, and photostability of the two cilostazol salts were also determined. The dissolution profiles in various pH conditions and pharmacokinetic studies in rats were compared with those of cilostazol-free base.Results: The two cilostazol salts exhibited good physicochemical properties, such as nonhygroscopicity, stress stability, and photostability, which make it suitable for the preparation of pharmaceutical formulations. Both cilostazol mesylate and cilostazol besylate showed significantly improved dissolution rate and extent of drug release in the pH range 1.2–6.8 compared to the cilostazol-free base. In addition, after oral administration to rats, cilostazol mesylate and cilostazol besylate showed increases in Cmax and AUCt of approximately 3.65- and 2.87-fold and 3.88- and 2.94-fold, respectively, compared to cilostazol-free base.Conclusion: This study showed that two novel salts of cilostazol, such as cilostazol mesylate and cilostazol besylate, could be used to enhance its oral absorption. The findings warrant further preclinical and clinical studies on cilostazol mesylate and

  4. Hydrazine inhalation hepatotoxicity.

    Kao, Yung Hsiang; Chong, C H; Ng, W T; Lim, D

    2007-10-01

    Abstract Hydrazine is a hazardous chemical commonly used as a reactant in rocket and jet fuel cells. Animal studies have demonstrated hepatic changes after hydrazine inhalation. Human case reports of hydrazine inhalation hepatotoxicity are rare. We report a case of mild hepatotoxicity following brief hydrazine vapour inhalation in a healthy young man, which resolved completely on expectant management.

  5. Platelet Dysfunction in Patients with Chronic Myeloid Leukemia: Does Imatinib Mesylate Improve It?

    Olga Meltem Akay

    2016-05-01

    Full Text Available Objective: The aim of this study was to investigate the effects of imatinib mesylate on platelet aggregation and adenosine triphosphate (ATP release in chronic myeloid leukemia patients. Materials and Methods: Platelet aggregation and ATP release induced by 5.0 mM adenosine diphosphate, 0.5 mM arachidonic acid, 1.0 mg/ mL ristocetin, and 2 µg/mL collagen were studied by whole blood platelet lumi-aggregometer in 20 newly diagnosed chronic myeloid leukemia patients before and after imatinib mesylate treatment. Results: At the time of diagnosis, 17/20 patients had abnormal platelet aggregation results; 8 (40% had hypoactivity, 6 (30% had hyperactivity, and 3 (15% had mixed hypo- and hyperactivity. Repeat platelet aggregation studies were performed after a mean of 19 months (min: 5 months-max: 35 months in all patients who received imatinib mesylate during this period. After therapy, 18/20 (90% patients had abnormal laboratory results; 12 (60% had hypoactive platelets, 4 (20% had mixed hypo- and hyperactive platelets, and 2 (10% had hyperactive platelets. Three of the 8 patients with initial hypoactivity remained hypoactive, while 2 developed a mixed picture, 2 became hyperactive, and 1 normalized. Of the 6 patients with initial hyperactivity, 4 became hypoactive and 2 developed a mixed pattern. All of the 3 patients with initial hypo- and hyperactivity became hypoactive. Finally, 2 of the 3 patients with initial normal platelets became hypoactive while 1 remained normal. There was a significant decrease in ristocetin-induced platelet aggregation after therapy (p0.05. Conclusion: These findings indicate that a significant proportion of chronic myeloid leukemia patients have different patterns of platelet function abnormalities and imatinib mesylate has no effect on these abnormalities, with a significant impairment in ristocetin-induced platelet aggregation.

  6. Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

    Desjardins, Annick; Quinn, Jennifer A; Vredenburgh, James J; Sathornsumetee, Sith; Friedman, Allan H; Herndon, James E; McLendon, Roger E; Provenzale, James M; Rich, Jeremy N; Sampson, John H; Gururangan, Sridharan; Dowell, Jeannette M; Salvado, August; Friedman, Henry S; Reardon, David A

    2007-05-01

    Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG). Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate. Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses. Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.

  7. Management of CML in the Pediatric Age Group: Imatinib Mesylate or SCT.

    El-Alfy, Mohsen S; Al-Haddad, Alaa M; Hamed, Ahmed A

    2010-12-01

    Management of CML has changed markedly since the introduction of tyrosine kinase inhibitors (TKIs). However stem cell transplantation (SCT) remains a valid therapeutic modality especially in developing countries due to its relatively lower cost. We aim to compare between imatinib mesylate and SCT as regard outcome in CML in the pediatric age group. Forty-eight patients with newly diagnosed CML in the chronic phase, aged 3 to 18 years were enrolled in this prospective study. Patients without a matched donor (Group I; N=30) were assigned to receive imatinib mesylate at a dose of 340mg÷m2÷day, while patients with a fully matched related donor (Group II; N=18), were offered SCT. Response (hematologic, cytogenetic and molecular), side effects and survival were analyzed. Complete hematologic response was obtained in 97% of the patients in group I and 94% in group II. Major cytogenetic response (CyR) was obtained in 80% of patients in group I and 100% in group II. Complete CyR was 57% in group I and 64% in group II. Major molecular response (MMR) was 36% in group I and 50% in group II with no significant difference between both groups. Six years overall survival (OS) was 87% in the 1st group and 61% in the 2nd group (pSCT group (55% had GVHD and 78% had infection). Imatinib mesylate has a superior OS and EFS than SCT in children. It is generally safe and well tolerated. Imatinib mesylate should be the 1st line treatment of pediatric patients with CML in the chronic phase. CML- Imatinib- SCT- Pediatrics.

  8. Homologous recombination induced by doxazosin mesylate and saw palmetto in the Drosophila wing-spot test.

    Gabriel, Katiane Cella; Dihl, Rafael Rodrigues; Lehmann, Mauricio; Reguly, Maria Luiza; Richter, Marc François; Andrade, Heloisa Helena Rodrigues de

    2013-03-01

    Benign prostatic hyperplasia (BPH) is the most common tumor in men over 40 years of age. Acute urinary retention (AUR) is regarded as the most serious hazard of untreated BPH. α-Blockers, such as doxazosin mesylate, and 5-α reductase inhibitors, such as finasteride, are frequently used because they decrease both AUR and the need for BPH-related surgery. An extract of the fruit from American saw palmetto plant has also been used as an alternative treatment for BPH. The paucity of information available concerning the genotoxic action of these compounds led us to assess their activity as inducers of different types of DNA lesions using the somatic mutation and recombination test in Drosophila melanogaster. Finasteride did not induce gene mutation, chromosomal mutation or mitotic recombination, which means it was nongenotoxic in our experimental conditions. On the other hand, doxazosin mesylate and saw palmetto induced significant increases in spot frequencies in trans-heterozygous flies. In order to establish the actual role played by mitotic recombination and by mutation in the genotoxicity observed, the balancer-heterozygous flies were also analyzed, showing no increment in the total spot frequencies in relation to the negative control, for both drugs. Doxazosin mesylate and saw palmetto were classified as specific inducers of homologous recombination in Drosophila proliferative cells, an event linked to the loss of heterozygosity. Copyright © 2011 John Wiley & Sons, Ltd.

  9. Inhalant allergies in children.

    Mims, James W; Veling, Maria C

    2011-06-01

    Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Inhalant Abuse and Dextromethorphan.

    Storck, Michael; Black, Laura; Liddell, Morgan

    2016-07-01

    Inhalant abuse is the intentional inhalation of a volatile substance for the purpose of achieving an altered mental state. As an important, yet underrecognized form of substance abuse, inhalant abuse crosses all demographic, ethnic, and socioeconomic boundaries, causing significant morbidity and mortality in school-aged and older children. This review presents current perspectives on epidemiology, detection, and clinical challenges of inhalant abuse and offers advice regarding the medical and mental health providers' roles in the prevention and management of this substance abuse problem. Also discussed is the misuse of a specific "over-the-counter" dissociative, dextromethorphan. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The synthesis of [[sup 2]H],[[sup 3]H], and [[sup 14]C]-labeled 8[beta]-[(methylthio)methyl]-6-propylergoline mesylate (pergolide mesylate), a potent, long-acting dopamine agonist

    Wheeler, W.J.; Kau, D.L.K.; Bach, N.J. (Lilly (Eli) and Co., Indianapolis, IN (United States). Lilly Research Labs.)

    1990-03-01

    The [[sup 3]H]- and two[[sup 14]C]-isopomers of 8[beta]-[(methylthio)methyl]-6-propylergoline mesylate (pergolide mesylate) have been synthesized. The [[sup 3]H]-derivative was synthesized by the palladium catalyzed tritiation of the corresponding 6-allyl derivative. Reaction of 8[beta]-[(methylthio)methyl]-ergoline with 1-[[sup 14]C]-1-propyl bromide yielded pergolide labeled in the 6-propyl group. Alternatively, reaction of 8[beta]-mesyloxy-6-propylergoline with [[sup 14]C]-sodium cyanide, followed by base hydrolysis, yielded 8 [beta]-carboxy-6-propylergoline-[[sup 14]C], which was subsequently converted to pergolide mesylate radiolabeled in the 17-position via a four step sequence. (Author).

  12. Objective measurement of inhaler inhalation flow profile using acoustic methods

    Lacalle, H.; Taylor, T.E.; Marco, S.; Reilly, R.B.

    2016-07-01

    Patients with asthma and chronic obstructive pulmonary diseases (COPD) are mostly treated with inhalers that deliver medication directly to their airways. Drug delivery from dry powder inhalers (DPIs) is very much reliant on the inhalation manoeuvre, specifically the peak inspiratory flow rate (PIFR), inspiratory capacity (IC) and inhalation rise time (IRT) of the inhalation. It has been widely reported that patients may not follow correct inhalation technique while using their inhaler. In this study, a novel acoustic method is proposed to accurately estimate inhalation flow profile using only one inhalation recording for calibration. An Ellipta DPI was placed inside an airtight container with a spirometer connected in order to measure inhalation flow parameters. An acoustic recording device (Inhaler Compliance Assessment (INCA)) was also attached to the DPI. Inhalation audio and flow signals were recorded simultaneously. The data were collected from 20 healthy subjects while performing inhaler inhalations at a range of inspiratory flow rates. A power law regression model was computed to obtain the relationship between the acoustic envelope of the inhalation and flow profile of each recording. Each model was tested on the remaining audio signals to estimate flow profile. The average estimation error was found to be 10.5±0.3% for estimating flow profile from audio signals. Inhalation flow profile parameters (PIFR, IC and IRT) could then be measured from the estimated flow profile with high accuracy giving information on user inhalation technique. This method may assist in improving patient inhaler adherence and overall disease control. (Author)

  13. Gynecomastia during imatinib mesylate treatment for gastrointestinal stromal tumor: a rare adverse event

    Yan ZhongShu

    2011-11-01

    Full Text Available Abstract Background Imatinib mesylate has been the standard therapeutic treatment for chronic myeloid leukemia, advanced and metastatic gastrointestinal stromal tumor (GIST. It is well tolerated with mild adverse effects. Gynecomastia development during the course of treatment has been rarely reported. Methods Ninety-eight patients with advanced or recurrent GIST were treated with imatinib mesylate. Among the fifty-seven male patients six developed gynecomastia during the treatment. The lesions were confirmed by sonography. Sex hormone levels were determined in six patients with and without the presence of gynecomastia respectively. The patients with gynecomatia were treated with tamoxifene and the sex hormones were assayed before and after tamoxifene treatment. Results In patients with gynecomastia the lump underneath the bilateral nipples was 2.5 to 5 centimeters in diameter. Their serum free testosterone levels ranged between 356.61 and 574.60 ng/dl with a mean ± SD of 408.64 ± 82.06 ng/dl (95% CI 343.03~474.25 ng/dl, which is within the normal range. The level of serum estradiol was 42.89 ± 16.54 pg/ml (95% CI 29.66~56.12 pg/ml. Three patients had higher levels (43.79~71.21 pg/ml and the others' were within normal range of 27.00~34.91 pg/ml. Six patients without the development of gynecomastia had normal free testosterone. One patient died because of large tumor burden. The sex hormones had no significant changes before and after tamoxifene treatment.(P > 0.05 Conclusions Testosterone levels were not decreased in the six GIST patients with gynecomastia. Three patients had increased serum estradiol level which suggests that imbalance of sex hormones may be the cause of gynecomastia during treatment with imatinib mesylate.

  14. Inhalants in Peru.

    Lerner, R; Ferrando, D

    1995-01-01

    In Peru, the prevalence and consequences of inhalant abuse appear to be low in the general population and high among marginalized children. Inhalant use ranks third in lifetime prevalence after alcohol and tobacco. Most of the use appears to be infrequent. Among marginalized children, that is, children working in the streets but living at home or children living in the street, the problem of inhalant abuse is a serious problem. Among children working in the streets but living at home, the lifetime prevalence rate for inhalant abuse is high, ranging from 15 to 45 percent depending on the study being cited. For children living in the streets, the use of inhalant is even more severe. As mentioned earlier in this chapter, most of these street children use inhalants on a daily basis. The lack of research on the problem of inhalant abuse is a serious impediment to development of intervention programs and strategies to address this problem in Peru. Epidemiologic and ethnographic research on the nature and extent of inhalant abuse are obvious prerequisites to targeted treatment and preventive intervention programs. The urgent need for current and valid data is underscored by the unique vulnerability of the youthful population at risk and the undisputed harm that results from chronic abuse of inhalants. Nonetheless, it is important to mention several programs that work with street children. Some, such as the Information and Education Center for the Prevention of Drug Abuse, Generation, and Centro Integracion de Menores en Abandono have shelters where street children are offered transition to a less marginal lifestyle. Teams of street educators provide the children with practical solutions and gain their confidence, as well as offer them alternative socialization experiences to help them survive the streets and avoid the often repressive and counterproductive environments typical of many institutions. Most of the children who go through these programs tend to abandon

  15. Formulation and In Vitro, In Vivo Evaluation of Effervescent Floating Sustained-Release Imatinib Mesylate Tablet

    Kadivar, Ali; Kamalidehghan, Behnam; Javar, Hamid Akbari; Davoudi, Ehsan Taghizadeh; Zaharuddin, Nurul Dhania; Sabeti, Bahareh; Chung, Lip Yong; Noordin, Mohamed Ibrahim

    2015-01-01

    Introduction Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets. Methodology Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M), with Sodium alginate (SA) and Carbomer 934P (CP) as release-retarding polymers, sodium bicarbonate (NaHCO3) as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec) in 0.1 N HCl (pH 1.2) at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted. Results and Discussion Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec). Thus, formulated SR tablets preserved persistent

  16. Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet.

    Ali Kadivar

    Full Text Available Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT. Conventional imatinib mesylate (Gleevec tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.Floating sustained-release Imatinib mesylate tablets were prepared using the wet granulation method. Tablets were formulated using Hydroxypropyl Methylcellulose (HPMC K4M, with Sodium alginate (SA and Carbomer 934P (CP as release-retarding polymers, sodium bicarbonate (NaHCO3 as the effervescent agent and lactose as a filler. Floating behavior, in vitro drug release, and swelling index studies were conducted. Initial and total drug release duration was compared with a commercial tablet (Gleevec in 0.1 N HCl (pH 1.2 at 37 ± 0.5°C for 24 hours. Tablets were then evaluated for various physical parameters, including weight variation, thickness, hardness, friability, and drug content. Consequently, 6 months of physical stability studies and in vitro gastro-retentive studies were conducted.Statistical data analysis revealed that tablets containing a composition of 14.67% w/w HPMC K4M, 10.67%, w/w Na alginate, 1.33%, w/w Carbomer 934P and 9.33%, w/w NaHCO3 produced the most favorable formulation to develop 24-hour sustained-release tablets with optimum floating behavior and satisfactory physicochemical characteristics. Furthermore, in vitro release study revealed that the formulated SR tablet had significantly lower Cmax and higher Tmax compared to the conventional tablet (Gleevec. Thus, formulated SR tablets preserved persistent concentration of plasma up to 24 hours

  17. The clinical effect of deferoxamine mesylate on edema after intracerebral hemorrhage.

    Yu, Yao; Zhao, Wei; Zhu, Chunpeng; Kong, Zhiping; Xu, Yan; Liu, Guangzhi; Gao, Xuguang

    2015-01-01

    It has been shown that 3 days of 62 mg/kg/day deferoxamine infusion (maximum dose not to exceed 6000 mg/day) is safe and tolerated by intracerebral hemorrhage (ICH) patients. The aim of this study was to investigate the efficacy of deferoxamine mesylate for edema resolution and hematoma absorption after ICH. From February 2013 to May 2014, spontaneous ICH patients diagnosed by computed tomography (CT) within 18 hours of onset were evaluated. Patients were randomly divided into two groups: an experimental group and a control group. The treatment of the two groups was similar except that the experimental group received deferoxamine mesylate. Patients were evaluated by CT and neurology scale at the time of admission, and on the fourth, eighth, and fifteenth day (or at discharge) after admission. Patients were followed up for the first 30 days and clinical data of the two groups were compared. Forty-two patients completed 30 days of follow-up by May 2014; 21 cases in the experimental group and 21 cases in the control group. The control group's relative edema volume on the fifteenth day (or discharge) was 10.26 ± 17.54, which was higher than the experimental group (1.91 ± 1.94; P edema volume on the fourth, eighth, and fifteenth day (or discharge) was higher than the experimental group (P edema after ICH, although further investigation is required to form definitive conclusions. Chinese Clinical Trial Registry ChiCTR-TRC-14004979.

  18. Effects of co-dergocrine mesylate (Hydergine) in multi-infarct dementia as evaluated by positron emission tomography

    Nagasawa, Haruo; Kogure, Kyuya; Kawashima, Koichiro; Ido, Tatsuo; Itoh, Masatoshi; Hatazawa, Jun.

    1990-01-01

    Three female patients aged from 74 to 79 with multi-infarct dementia were studied using positron emission tomography (PET) to assess the effect of co-dergocrine mesylate (Hydergine) on cerebral glucose metabolism. The cerebral glucose utilization (CMRGlc) of each patient was evaluated by PET scan using 2-deoxy-[ 18 F]-2-fluoro-D-glucose (FDG). Following the first PET study, 0.04 mg/kg of co-dergocrine mesylate was injected intravenously with 250 ml saline solution, and then the second PET study was performed. The CMRGlc was determined from the images of the PET scan and the radioactivity of 18 F in the plasma. After the administration of co-dergocrine mesylate, the value of CMRGlc increased significantly in the cerebral cortex (p<0.01 and p<0.05) and basal ganglia (p<0.05) compared with values before the administration, but no significant increase was found in the centrum semiovale. These results suggest that co-dergocrine mesylate stimulates glucose metabolism of neurons in the human brain. (author)

  19. Olodaterol Oral Inhalation

    ... in a class of medications called long-acting beta-agonists (LABAs). It works by relaxing and opening ... the inhaler upright with the yellow cap closed. Turn the clear base in the direction of the ...

  20. Pirbuterol Acetate Oral Inhalation

    ... Pirbuterol is in a class of medications called beta-agonist bronchodilators. It works by relaxing and opening ... cleaning. Once a week, remove the mouthpiece cover, turn the inhaler upside down and wipe the mouthpiece ...

  1. Cromolyn Oral Inhalation

    ... your doctor.Cromolyn oral inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Your doctor will prescribe ...

  2. Ipratropium Oral Inhalation

    ... with the clear end pointing upward. Place the metal canister inside the clear end of the inhaler. ... do not discard it in an incinerator or fire.Unneeded medications should be disposed of in special ...

  3. Nicotine Oral Inhalation

    ... with a smoking cessation program, which may include support groups, counseling, or specific behavioral change techniques. Nicotine inhalation ... and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or ...

  4. Radioactive gas inhalator

    LeMon, D.E.

    1975-01-01

    An ''inhalator'', or more particularly an apparatus for permitting a patient to inhale a radioactive gas in order to provide a diagnostic test of the patient's lung area, is described. The disclosed apparatus provides a simple, trouble-free mechanism for achieving this result; and, furthermore, provides an improved testing method. Moreover, the disclosed apparatus has the capability of gradually introducing the test condition in a manner that makes it easy for the patient to become acclimated to it. (U.S.)

  5. Identification of cysteine-644 as the covalent site of attachment of dexamethasone 21-mesylate to murine glucocorticoid receptors in WEHI-7 cells

    Smith, L.I.; Bodwell, J.E.; Mendel, D.B.; Ciardelli, T.; North, W.G.; Munck, A.

    1988-01-01

    Dexamethasone 21-mesylate is a highly specific synthetic glucocorticoid derivative that binds covalently to glucocorticoid receptors via sulfhydryl groups. The authors have identified the amino acid that reacts with the dexamethasone 21-mesylate by using enzymatic digestion and microsequencing for radiolabel. Nonactivated glucocorticoid receptors obtained from labeling intact WEHI-7 mouse thymoma cells with [ 3 H]dexamethasone 21-mesylate were immunopurified and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Trypsin digestion followed by reversed-phase high-performance liquid chromatography (reversed-phase HPLC) produced a single [ 3 H]dexamethasone 21-mesylate labeled peptide. Automated Edman degradation of this peptide revealed that the [ 3 H]dexamethasone 21-mesylate was located at position 5 from the amino terminus. Dual-isotope labeling studies with [ 3 H]dexamethasone 21-mesylate and [ 35 S]methionine demonstrated that this peptide contained methionine. Staphylococcus aureus V8 protease digestion of [ 3 H]dexamethasone 21-mesylate labeled steroid-binding subunits generated a different radiolabeled peptide containing label at position 7 from the amino terminus. On the basis of the published amino acid sequence of the murine glucocorticoid receptor, their data clearly identify cysteine-644 as the single residue in the steroid-binding domain that covalently binds dexamethasone 21-mesylate. They have confirmed this finding by demonstrating that a synthetic peptide representing the amino acid sequence 640-650 of the murine glucocorticoid receptor behaves in an identical manner on reversed-phase HPLC as the trypsin-generated peptide from intact cells

  6. Cytoprotective effect of imatinib mesylate in non-BCR-ABL-expressing cells along with autophagosome formation

    Ohtomo, Tadashi; Miyazawa, Keisuke; Naito, Munekazu; Moriya, Shota; Kuroda, Masahiko; Itoh, Masahiro; Tomoda, Akio

    2010-01-01

    Treatment with imatinib mesylate (IM) results in an increased viable cell number of non-BCR-ABL-expressing cell lines by inhibiting spontaneous apoptosis. Electron microscopy revealed an increase of autophagosomes in response to IM. IM attenuated the cytotoxic effect of cytosine arabinoside, as well as inhibiting cell death with serum-deprived culture. Cytoprotection with autophagosome formation by IM was observed in various leukemia and cancer cell lines as well as normal murine embryonic fibroblasts (MEFs). Complete inhibition of autophagy by knockdown of atg5 in the Tet-off atg5 -/- MEF system attenuated the cytoprotective effect of IM, indicating that the effect is partially dependent on autophagy. However, cytoprotection by IM was not mediated through suppression of ROS production via mitophagy, ER stress via ribophagy, or proapoptotic function of ABL kinase. Although the target tyrosine kinase(s) of IM remains unclear, our data provide novel therapeutic possibilities of using IM for cytoprotection.

  7. Synthesis of chitosan-PEO hydrogels via mesylation and regioselective Cu(I)-catalyzed cycloaddition.

    Tirino, Pasquale; Laurino, Rosaria; Maglio, Giovanni; Malinconico, Mario; d'Ayala, Giovanna Gomez; Laurienzo, Paola

    2014-11-04

    In this work, a well-defined hydrogel was developed by coupling chitosan with PEO through "click chemistry". Azide functionalities were introduced onto chitosan, through mesylation of C-6 hydroxyl groups, and reacted with a di-alkyne PEO by a regioselective Cu(I)-catalyzed cycloaddition. This synthetic approach allowed us to obtain a hydrogel with a controlled crosslinking degree. In fact, the extent of coupling is strictly dependent on the amount of azido groups on chitosan, which in turn can be easily modulated. The obtained hydrogel, with a crosslinking degree of around 90%, showed interesting swelling properties. With respect to chitosan hydrogels reported in literature, a considerably higher equilibrium uptake was reached (940%). The possibility to control the crosslinking degree of hydrogel and its capability to rapidly absorb high amounts of water make this material suitable for several applications, such as controlled drug release and wound healing. Copyright © 2014. Published by Elsevier Ltd.

  8. Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes.

    Stagno, Fabio; Stella, Stefania; Spitaleri, Antonio; Pennisi, Maria Stella; Di Raimondo, Francesco; Vigneri, Paolo

    2016-01-01

    The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment.

  9. Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

    Sohn, Eun Jeong; Kim, Dae Won; Kim, Young Nam; Kim, So Mi; Lim, Soon Sung; Kang, Tae-Cheon; Kwon, Hyeok Yil; Kim, Duk-Soo; Cho, Sung-Woo; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Hwang, Hyun Sook; Choi, Soo Young

    2011-01-01

    Research highlights: → We studied effects of pergolide mesylate (PM) on in vitro and in vivo transduction of PEP-1-catalase. → PEP-1-catatase inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. → PM enhanced the transduction of PEP-1-catalase into HaCaT cells and skin tissue. → PM increased anti-inflammatory activity of PEP-1-catalase. → PM stimulated therapeutic action of anti-oxidant enzyme catalase in oxidative-related diseases. -- Abstract: The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1β, and tumor necrosis factor-α induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.

  10. Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

    Sohn, Eun Jeong; Kim, Dae Won; Kim, Young Nam; Kim, So Mi [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Lim, Soon Sung [Department of Food Science and Nutrition and RIC Center, Hallym University, Chunchon 200-702 (Korea, Republic of); Kang, Tae-Cheon [Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Kwon, Hyeok Yil [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Kim, Duk-Soo [Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 330-090 (Korea, Republic of); Cho, Sung-Woo [Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Hwang, Hyun Sook, E-mail: wazzup@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2011-03-18

    Research highlights: {yields} We studied effects of pergolide mesylate (PM) on in vitro and in vivo transduction of PEP-1-catalase. {yields} PEP-1-catatase inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation. {yields} PM enhanced the transduction of PEP-1-catalase into HaCaT cells and skin tissue. {yields} PM increased anti-inflammatory activity of PEP-1-catalase. {yields} PM stimulated therapeutic action of anti-oxidant enzyme catalase in oxidative-related diseases. -- Abstract: The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1{beta}, and tumor necrosis factor-{alpha} induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.

  11. Inhaled americium dioxide

    Park, J.F.

    1982-01-01

    This project includes experiments to determine the effects of Zn-DTPA therapy on the retention, translocation and biological effects of inhaled 241 AmO 2 . Beagle dogs that received inhalation exposure to 241 AmO 2 developed leukopenia, clincial chemistry changes associated with hepatocellular damage, and were euthanized due to respiratory insufficiency caused by radiation pneumonitis 120 to 131 days after pulmonary deposition of 22 to 65 μCi 241 Am. Another group of dogs that received inhalation exposure to 241 AmO 2 and were treated daily with Zn-DTPA had initial pulmonary deposition of 19 to 26 μCi 241 Am. These dogs did not develop respiratory insufficiency, and hematologic and clinical chemistry changes were less severe than in the non-DTPA-treated dogs

  12. Know How to Use Your Asthma Inhaler

    Full Text Available ... KB] Using a metered dose inhaler (inhaler in mouth) Your browser does not support iframes Using a metered dose inhaler (inhaler in mouth) [PDF – 370 KB] Your browser does not support ...

  13. Long-term remission in BCR/ABL-positive AML-M6 patient treated with Imatinib Mesylate.

    Pompetti, Franca; Spadano, Antonio; Sau, Antonella; Mennucci, Antonio; Russo, Rosa; Catinella, Virginia; Franchi, Paolo Guanciali; Calabrese, Giuseppe; Palka, Giandomenico; Fioritoni, Giuseppe; Iacone, Antonio

    2007-04-01

    BCR/ABL-positive acute myeloid leukemia (AML) is a rare disease, characterized by a poor prognosis, with resistance to induction chemotherapy and frequent relapses in responsive patients. Here we report a case of BCR/ABL-positive AML-M6 who, after relapse, was treated with Imatinib Mesylate (600 mg/die) and within 4 months achieved a cytogenetic and molecular complete response. After more than 4 years of continuous Imatinib therapy, nested RT-PCR for BCR/ABL is persistently negative. The case reported shows that the response obtained with Imatinib Mesylate in BCR/ABL-positive AML may be long lasting, offering a chance of successful treatment for this poor prognosis group of patients.

  14. Food hypersensitivity by inhalation

    Bahna Sami L

    2009-02-01

    Full Text Available Abstract Though not widely recognized, food hypersensitivity by inhalation can cause major morbidity in affected individuals. The exposure is usually more obvious and often substantial in occupational environments but frequently occurs in non-occupational settings, such as homes, schools, restaurants, grocery stores, and commercial flights. The exposure can be trivial, as in mere smelling or being in the vicinity of the food. The clinical manifestations can vary from a benign respiratory or cutaneous reaction to a systemic one that can be life-threatening. In addition to strict avoidance, such highly-sensitive subjects should carry self-injectable epinephrine and wear MedicAlert® identification. Asthma is a strong predisposing factor and should be well-controlled. It is of great significance that food inhalation can cause de novo sensitization.

  15. Inhalation of uranium ores

    Stuart, B.O.; Jackson, P.O.

    1975-01-01

    In previous studies the biological dispositions of individual long-lived alpha members of the uranium chain ( 238 U, 234 U and 230 Th) were determined during and following repeated inhalation exposures of rats to pitchblende (26 percent U 3 O 8 ) ore. Although finely dispersed ore in secular equilibrium was inhaled, 230 Th/ 234 U radioactivity ratios in the lungs rose from 1.0 to 2.5 during 8 weeks of exposures and increased to 9.2 by four months after cessation of exposures. Marked non-equilibrium levels were also found in the tracheobronchial lymph nodes, kidneys, liver, and femur. Daily exposures of beagle dogs to high levels of this ore for 8 days resulted in lung 230 Th/ 234 U ratios of >2.0. Daily exposures of dogs to lower levels (0.1 mg/1) for 6 months, with sacrifice 15 months later, resulted in lung and thoracic lymph node 230 Th/ 234 U ratios ranging from 3.6 to 9 and nearly 7, respectively. The lungs of hamsters exposed to carnotite (4 percent U 3 O 8 ) ore in current lifespan studies show 230 Th/ 234 U ratios as high as 2.0 during daily inhalation of this ore in secular equilibrium. Beagle dogs sacrificed after several years of daily inhalations of the same carnotite ore plus radon daughters also showed marked non-equilibrium ratios of 230 Th/ 234 U, ranging from 5.6 to 7.4 in lungs and 6.2 to 9.1 in thoracic lymph nodes. This pattern of higher retention of 230 Th than 234 U in lungs, thoracic lymph nodes, and other tissues is thus consistent for two types of uranium ore among several species and suggests a reevaluation of maximum permissible air concentrations of ore, currently based only on uranium content

  16. Inhaled transuranics in rodents

    Sanders, C.L.

    1983-01-01

    This project examines the interactions of external and internal radiation from mixtures of radionuclides present within the nuclear fuel inventory. The objective of the project is to evaluate the effects of mixed radiation insults, using key radiation sources as indicative of overall processes that may occur following release of nuclear fuel into the air. Previously initiated studies of immunological effects of plutonium inhalation are also being completed as part of this project

  17. Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial

    Grunberg, Steven M; Rolski, Janusz; Strausz, Janos

    2009-01-01

    in the control group. The most common serious adverse events were neutropenia (n=5 [3%] in the control group, n=3 [1%] in the single-dose oral casopitant mesylate group, and n=11 [4%] in the 3-day intravenous plus oral casopitant mesylate group), febrile neutropenia (n=1 [

  18. Spectrophotometric Determination of Gemifloxacin Mesylate in Pharmaceutical Formulations Through Ion-Pair Complex Formation

    Marothu Vamsi Krishna

    2008-01-01

    Full Text Available Four simple and sensitive ion-pairing spectrophotometric methods have been described for the assay of gemifloxacin mesylate (GFX either in pure form or in pharmaceutical formulations. The developed methods involve formation of colored chloroform extractable ion-pair complexes of the drug with safranin O (SFN O and methylene blue (MB in basic medium; Napthol blue 12BR (NB 12BR and azocaramine G (AG in acidic medium. The extracted complexes showed absorbance maxima at 525, 650, 620 and 540 nm for SFN O, MB, NB 12BR and AG, respectively.Beer's law is obeyed in the concentration ranges 3-15, 4-20, 2-10 and 2-10 μg/mL with molar absorptivity of 2.81 × 104, 2.20 x 104, 4.02 × 104 and 4.15 × 104 L mole−1 cm−1 and relative standard deviation of 0.077, 0.104, 0.080 and 0.103% for SFN O, MB, NB 12BR and AG, respectively. These methods have been successfully applied for the assay of drug in pharmaceutical formulations. No interference was observed from common pharmaceutical adjuvants. Results of analysis were validated statistically and through recovery studies.

  19. Spectrophotometric Determination of Gemifloxacin Mesylate, Moxifloxacin Hydrochloride, and Enrofloxacin in Pharmaceutical Formulations Using Acid Dyes

    Ayman A. Gouda

    2014-01-01

    Full Text Available Simple, rapid, and extractive spectrophotometric methods were developed for the determination of some fluoroquinolones antibiotics: gemifloxacin mesylate (GMF, moxifloxacin hydrochloride (MXF, and enrofloxacin (ENF in pure forms and pharmaceutical formulations. These methods are based on the formation of ion-pair complexes between the basic drugs and acid dyes, namely, bromocresol green (BCG, bromocresol purple (BCP, bromophenol blue (BPB, bromothymol blue (BTB, and methyl orange (MO in acidic buffer solutions. The formed complexes were extracted with chloroform and measured at 420, 408, 416, 415, and 422 nm for BCG, BCP, BPB, BTB, and MO, respectively, for GMF; at 410, 415, 416, and 420 nm for BCP, BTB, BPB, and MO, respectively, for MXF; and at 419 and 414 nm for BCG and BTB, respectively, in case of ENF. The analytical parameters and their effects are investigated. Beer’s law was obeyed in the ranges 1.0–30, 1.0–20, and 2.0–24 μg mL−1 for GMF, MXF, and ENF, respectively. The proposed methods have been applied successfully for the analysis of the studied drugs in pure forms and pharmaceutical formulations. Statistical comparison of the results with the reference methods showed excellent agreement and indicated no significant difference in accuracy and precision.

  20. Effect of gamma-irradiation on biodegradable microspheres loaded with rasagiline mesylate

    Fernandez, Marcos; Barcia, Emilia; Negro, Sofia

    2016-01-01

    In the present study, the influence of gamma-irradiation was evaluated on the physicochemical characteristics and in vitro release of rasagiline mesylate (RM), a selective MAO-B inhibitor used in Parkinson's disease, from poly(D,L-lactide-co-glycolide) (PLGA) microspheres. Microspheres were prepared using PLGA 50:50 by the solvent evaporation technique (O/W emulsion). Microspheres were sterilized by gamma-irradiation and their influence was assessed by scanning electron microscopy (SEM), laser light diffraction, differential scanning calorimetry (DSC), X-ray diffraction (XRD), gel permeation chromatography (GPC), encapsulation efficiency (EE) and in vitro drug release. Gamma-irradiation of RM-loaded microspheres did not affect EE, DSC and XRD patterns. After gamma-irradiation, changes on the surface were observed by SEM, but no significant difference in mean particle size was observed. GPC measurements showed a decrease in molecular weight of the polymer after five days of in vitro release. The similarity factor value between irradiated and non-irradiates microspheres was <50, indicating the non-similarity of the release profiles. The sterilization technique had an effect on the integrity of polymeric system, significantly affecting in vitro release of RM from PLGA microspheres. Therefore, from our results we conclude that gamma-irradiation is not a suitable sterilization procedure for this formulation

  1. Quantitative determination of pefloxacin mesylate by residual-base neutralisation method

    HULIKALCHANDRA SHEKAR PRAMEELA

    2004-05-01

    Full Text Available This work describes two procedures based on residual base determination for the quantification of pefloxacin mesylate (PFM in bulk drug and in pharmaceutical products. In the first method involving titrimetry, the drug solution is treated with a measured excess of sodium hydroxide followed by back titration of the residual base with hydrochloric acid using a phenol red-bromothymol blue mixed indicator. The second spectrophotometrie method involves treatment of a fixed amount of sodium hydroxide – phenol red mixture with varying amounts of the drug, and measuring the decrease in the absorbance of the dye at 560 nm. In the titrimetric method, a reaction stoichiometry of 1:1 was found in the quantification range of 4–20 mg of drug. The spectrophotometric method allows the determination of PFM in the 5–40 mg ml-1 range. The molar absorptivity is 5.91¤103 l mol-1 cm-1 and the Sandell sensitivity is 56.37 ng cm-2. The methods were applied successfully to the determination of PFM in pharmaceutical preparations.

  2. In vitro effects of imatinib mesylate on radiosensitivity and chemosensitivity of breast cancer cells

    Weigel, Marion T; Maass, Nicolai; Mundhenke, Christoph; Dahmke, Linda; Schem, Christian; Bauerschlag, Dirk O; Weber, Katrin; Niehoff, Peter; Bauer, Maret; Strauss, Alexander; Jonat, Walter

    2010-01-01

    Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy effecting intracellular signal transduction. With the tyrosine kinase inhibitors new targeted drugs are available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of imatinib with standard chemotherapy could lead to increased cytoreduction. Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with imatinib and radiation. Changes in expression and phosphorylation of target receptors were detected using western blot. Cell proliferation, migration and apoptosis assays were performed combining imatinib with doxorubicin. The combination of imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected, but receptor phosphorylation was significantly inhibited when treated with imatinib. Combination of imatinib with standard chemotherapy lead to an additive effect on cell growth inhibition compared to single treatment. Imatinib treatment combined with radiotherapy leads in breast cancer cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy enhances cytoreductive effects. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy on the treatment of breast cancer

  3. Concurrent Male Gynecomastia and Testicular Hydrocele after Imatinib Mesylate Treatment of a Gastrointestinal Stromal Tumor

    Kim, Hawk; Chang, Heung-Moon; Ryu, Min-Hee; Kim, Tae-Won; Sohn, Hee-Jung; Kim, So-Eun; Kang, Hye-Jin; Park, Sarah; Lee, Jung-Shin

    2005-01-01

    We report a gastrointestinal stromal tumor (GIST) patient with male gynecomastia and testicular hydrocele after treatment with imatinib mesylate. A 42 yr-old male patient presented for management of hepatic masses. Two years earlier, he had undergone a small bowel resection to remove an intraabdominal mass later shown to be a GIST, followed by adjuvant radiation therapy. At presentation, CT scan revealed multiple hepatic masses, which were compatible with metastatic GIST, and he was prescribed imatinib 400 mg/day. During treatment, he experienced painful enlargement of the left breast and scrotal swelling. Three months after cessation of imatinib treatment, the tumors recurred, and, upon recommencing imatinib, he experienced painful enlargement of the right breast and scrotal swelling. He was diagnosed with male gynecomastia caused by decreased testosterone and non-communicative testicular hydrocele. He was given androgen support and a hydrocelectomy, which improved his gynecomastia. The mechanism by which imatinib induces gynecomastia and hydrocele is thought to be associated with an inhibition of c-KIT and platelet-derive growth factor. This is the first report, to our knowledge, describing concurrent male gynecomastia and testicular hydrocele after imatinib treatment of a patient with GIST. PMID:15953881

  4. Enhanced Silver Nanoparticle Chemiluminescence Method for the Determination of Gemifloxacin Mesylate using Sequential Injection Analysis

    Alarfaj, N.A.; Aly, F.A.; Tamimi, A.A.

    2013-01-01

    A sequential injection analysis (SIA) with chemiluminescence detection has been proposed for the determination of the antibiotic gemifloxacin mesylate (GFX). The developed method is based on the enhancement effect of silver nanoparticles (Ag NPs) on the chemiluminescence (CL) signal of luminol-potassium ferricyanide reaction in alkaline medium. The introduction of gemifloxacin in this system produced a significant decrease in the CL intensity in presence of (Ag NPs). The optimum conditions for CL emission were investigated. Linear relationship between the decrease in CL intensity and concentration was obtained in the range 0.01-1000 ng mL-1, (r = 0.9997) with detection limit of 2.0 pg mL-1 and quantification limit of 0.01 pg mL-1. The relative standard deviation was 1.3 %. The proposed method was employed for the determination of gemifloxacin in bulk drug, in its pharmaceutical dosage forms and biological fluids such as human serum and urine. The interference of some common additive compounds such as glucose, lactose, starch, talc and magnesium stearate was investigated, and no interference was found from these excipients. The obtained SIA results were statistically compared with those obtained from a reported method and did not show any significant difference at confidence level 95%. (author)

  5. Know How to Use Your Asthma Inhaler

    Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... inhaler with a spacer Your browser does not support iframes Using a metered dose inhaler with a ...

  6. "Antifibrotic effect after low-dose imatinib mesylate treatment in patients with nephrogenic systemic fibrosis: An open-label non-randomized, uncontrolled clinical trial"

    Elmholdt, Tina Rask; Olesen, Anne Braae

    2011-01-01

    Background Nephrogenic systemic fibrosis is a disease affecting the connective tissue of the skin and internal organs in patients with renal failure. No effective treatments are available. Objectives To investigate if the tyrosine kinase inhibitor, imatinib mesylate was effective in patients...... Imatinib mesylate may be an effective drug in the treatment of skin fibrosis in moderate to severe NSF cases, even at reduced doses. We found a positive clinical effect on the skin, but no convincing improvement of the joint mobility. Only few patients could be recruited limiting the interpretation...

  7. Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity.

    Basciani, Sabrina; Brama, Marina; Mariani, Stefania; De Luca, Gabriele; Arizzi, Mario; Vesci, Loredana; Pisano, Claudio; Dolci, Susanna; Spera, Giovanni; Gnessi, Lucio

    2005-03-01

    Leydig cell tumors are usually benign tumors of the male gonad. However, if the tumor is malignant, no effective treatments are currently available. Leydig cell tumors express platelet-derived growth factor (PDGF), kit ligand and their respective receptors, PDGFR and c-kit. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors. Imatinib caused concentration-dependent decreases in the viability of Leydig tumor cell lines, which coincided with apoptosis and inhibition of proliferation and ligand-stimulated phosphorylation of c-kit and PDGFRs. Mice bearing s.c. allografts of a Leydig tumor cell line treated with imatinib p.o., had an almost complete inhibition of tumor growth, less tumor cell proliferation, increased apoptosis, and a lesser amount of tumor-associated mean vessel density compared with controls. No drug-resistant tumors appeared during imatinib treatment but tumors regrew after drug withdrawal. Human Leydig cell tumors showed an intense expression of the phosphorylated form of c-kit and a less intense expression of phosphorylated PDGFRs. No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy.

  8. Reversal of soft-tissue local anesthesia with phentolamine mesylate in adolescents and adults.

    Hersh, Elliot V; Moore, Paul A; Papas, Athena S; Goodson, J Max; Navalta, Laura A; Rogy, Siegfried; Rutherford, Bruce; Yagiela, John A

    2008-08-01

    The authors conducted two multicenter, randomized, double-blinded, controlled Phase III clinical trials to study the efficacy and safety of phentolamine mesylate (PM) in shortening the duration and burden of soft-tissue anesthesia. The study involved 484 subjects who received one of four commercially available local anesthetic solutions containing vasoconstrictors for restorative or scaling procedures. On completion of the dental procedure, subjects randomly received a PM or a sham injection (an injection in which a needle does not penetrate the soft tissue) in the same site as the local anesthetic injection. The investigators measured the duration of soft-tissue anesthesia by using standardized lip- and tongue-tapping procedures every five minutes for five hours. They also evaluated functional measures and subject-perceived altered function, sensation, appearance and safety. Median recovery times in the lower lip and tongue for subjects in the PM group were 70 minutes and 60 minutes, respectively. Median recovery times in the lower lip and tongue for subjects in the sham group were 155 minutes and 125 minutes, respectively. Upper lip median recovery times were 50 minutes for subjects in the PM group and 133 minutes for subjects in the sham group. These differences were significant (P < .0001). Recovery from actual functional deficits and subject-perceived altered function, sensation and appearance also showed significant differences between the PM and the sham groups. PM was efficacious and safe in reducing the duration of local anesthetic- induced soft-tissue numbness and its associated functional deficits. Clinicians can use PM to accelerate reversal of soft-tissue anesthesia and the associated functional deficits.

  9. Dihydroergotamine mesylate-loaded dissolving microneedle patch made of polyvinylpyrrolidone for management of acute migraine therapy.

    Tas, Cetin; Joyce, Jessica C; Nguyen, Hiep X; Eangoor, Padmanabhan; Knaack, Jennifer S; Banga, Ajay K; Prausnitz, Mark R

    2017-12-28

    Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability. In this study, we developed a dissolving microneedle patch (MNP) made of polyvinylpyrrolidone, due to its high aqueous solubility and solubility enhancement properties, using a MNP design previously shown to be painless and simple to administer. DHE-loaded MNPs were shown to have a content uniformity of 108±9% with sufficient mechanical strength for insertion to pig skin ex vivo and dissolution within 2min. In vivo pharmacokinetic studies were carried out on hairless rats, and DHE plasma levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under curve (AUC) value after DHE delivery by MNP (1259±917ng/mL min) was not significantly different (p>0.05) as compared to subcutaneous injection, with a relative bioavailability of 97%. Also, appreciable plasma levels of DHE were seen within 5min for both delivery methods and t max value of MNPs (38±23min) showed no significant difference (p>0.05) compared to subcutaneous injection (24±13min). These results suggest that DHE-loaded MNPs have promise as an alternative DHE delivery method that can be painlessly self-administered with rapid onset and high bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. In vitro inhibitory effects of imatinib mesylate on stromal cells and hematopoietic progenitors from bone marrow

    P.B. Soares

    2013-01-01

    Full Text Available Imatinib mesylate (IM is used to treat chronic myeloid leukemia (CML because it selectively inhibits tyrosine kinase, which is a hallmark of CML oncogenesis. Recent studies have shown that IM inhibits the growth of several non-malignant hematopoietic and fibroblast cells from bone marrow (BM. The aim of the present study was to evaluate the effects of IM on stromal and hematopoietic progenitor cells, specifically in the colony-forming units of granulocyte/macrophage (CFU-GM, using BM cultures from 108 1.5- to 2-month-old healthy Swiss mice. The results showed that low concentrations of IM (1.25 µM reduced the growth of CFU-GM in clonogenic assays. In culture assays with stromal cells, fibroblast proliferation and α-SMA expression by immunocytochemistry analysis were also reduced in a concentration-dependent manner, with a survival rate of approximately 50% with a dose of 2.5 µM. Cell viability and morphology were analyzed using MTT and staining with acrydine orange/ethidium bromide. Most cells were found to be viable after treatment with 5 µM IM, although there was gradual growth inhibition of fibroblastic cells while the number of round cells (macrophage-like cells increased. At higher concentrations (15 µM, the majority of cells were apoptotic and cell growth ceased completely. Oil red staining revealed the presence of adipocytes only in untreated cells (control. Cell cycle analysis of stromal cells by flow cytometry showed a blockade at the G0/G1 phases in groups treated with 5-15 µM. These results suggest that IM differentially inhibits the survival of different types of BM cells since toxic effects were achieved.

  11. Exubera. Inhale therapeutic systems.

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  12. Inhaled plutonium nitrate in dogs

    Dagle, G.E.; Cannon, W.C.; Ragan, H.A.; Watson, C.R.; Stevens, D.L.; Cross, F.T.; Dionne, P.J.; Harrington, T.P.

    1978-01-01

    Beagle dogs given a single inhalation exposure to 239 Pu(NO 3 ) 4 are being observed for life-span dose-effect relationships. Lymphopenia occurred at the two highest dosage levels as early as 1 mo following exposure and was associated with neutropenia and reduction in numbers of circulatory monocytes by 4 mo postexposure. Radiation pneumonitis developed in one dog at the highest dosage level at 14 mo postexposure. More rapid translocation to skeleton and liver occurred following inhalation of 238 Pu(NO 3 ) 4 than after 239 Pu(NO 3 ) 4 inhalation

  13. Imatinib mesylate is effective in children with chronic myelogenous leukemia in late chronic and advanced phase and in relapse after stem cell transplantation

    Millot, F; Guilhot, J; Nelken, B; Leblanc, T; De Bont, ES; Bekassy, AN; Gadner, H; Sufliarska, S; Stary, J; Gschaidmeier, H; Guilhot, F; Suttorp, M

    A multicentric phase 2 study was conducted to determine the efficiency and the tolerance of imatinib mesylate in children with chronic myelogenous leukemia (CML) in advanced phase of the disease, in relapse after stem cell transplantation, or in case of failure to an interferon a-based regimen. In

  14. Population pharmacokinetics of imatinib mesylate and its metabolite in children and young adults.

    Menon-Andersen, Divya; Mondick, John T; Jayaraman, Bhuvana; Thompson, Patrick A; Blaney, Susan M; Bernstein, Mark; Bond, Mason; Champagne, Martin; Fossler, Michael J; Barrett, Jeffrey S

    2009-01-01

    Imatinib mesylate (Gleevec) is a small molecule tyrosine kinase inhibitor approved for use in the management of chronic myeloid leukemia in adults and children and in gastrointestinal stromal tumors in adults. Population pharmacokinetic (PPK) studies evaluating the effect of population covariates on the pharmacokinetics of imatinib and its active metabolite have been developed in adults with chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). However, this still remains to be described in children. The objectives of the analysis were to develop a PPK model of imatinib and its active metabolite, CGP74588, to describe exposure in children and young adults and to identify covariates that are predictors of variability in disposition. Plasma concentrations from 26 subjects with Philadelphia (Ph+) leukemia (Phase I study) and 15 subjects with refractory solid tumors (Phase II study), who received oral imatinib at doses ranging from 260 to 570 mg/m(2), were available for the PPK analysis in NONMEM. Blood samples were drawn prior to dosing and over 24-48 h on days 1 and 8 of the studies. Covariates studied included weight, age, albumin, alanine aminotransferase and the study population. The pharmacokinetics of imatinib and CGP 74588 were well described by one and two compartment models, respectively. Total body weight was the only covariate found to significantly affect Cl/F and V/F. The final imatinib-CGP 74588 model is summarized as follows: CL/F (imatinib) (L/h) = 10.8 x (WT/70)(0.75), V/F (imatinib) (L) = 284 x (WT/70) and D1(duration of zero order absorption,imatinib) (h) = 1.67 and CL/F (CGP 74588) (L/h) = 9.65 x (WT/70)(0.75), V1/F (CGP 74588) (L) = 11.6 x (WT/70), Q (CGP 74588) (L/h) = 2.9 x (WT/70)(0.75) and V2/F (CGP 74588) (L) = 256*(WT/70). Model evaluation indicated that the final model was robust and satisfactory. Current imatinib dosing guidelines in pediatrics is based on the achievement of exposures consistent with doses known to be

  15. Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

    Waring Paul

    2004-10-01

    Full Text Available Abstract Background The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. Case presentation A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression

  16. Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

    Hughes, Brett; Yip, Desmond; Goldstein, David; Waring, Paul; Beshay, Victoria; Chong, Guan

    2004-01-01

    The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply) but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression occurred. This case illustrates that the brain can be a

  17. Inhaled Corticosteroids (ICSs) and Pregnancy

    ... of the airways in the lungs and reduce mucus production so that asthma attacks are less likely. ... of medicine that would be in the breast milk following inhalation is likely too small to cause ...

  18. Up regulation of K A I 1 gene expression and apoptosis effect of imatinib mesylate in gastric adenocarcinoma (AGS cell line

    eyed Ataollah Sadat Shandiz

    2016-02-01

    Full Text Available Objective: To evaluate the effect of imatinib mesylate on KAI1 gene expression and apoptosis properties in human gastric carcinoma AGS cell line. Methods: Cell viability was assessed by MTT assay and quantitative real time PCR method was applied for investigation of Bax, Bcl-2, and KAI1 gene expression in AGS cells. The quantity of KAI1, Bax, and Bcl-2 compared to GAPDH gene expressions were examined using the formula 2-∆∆Ct. Furthermore, cell apoptosis/necrosis was carried out by annexin V/PI staining and quantified with flow cytometry after treatment with imatinib. Results: Imatinib mesylate was showed to have a dose-dependent toxicity effect against AGS cells. KAI1/GAPDH gene expression ratios were 1.07 ± 0.02 (P > 0.05, 1.68 ± 0.19 (P > 0.05, 3.60 ± 0.55 (P < 0.05, 6.54 ± 0.27 (P < 0.001 for 20, 50, 80 and 100 μmol/L of imatinib concentrations. The mRNA levels of Bax detected by real-time PCR after treatment with imatinib mesylate were significantly increased. Also, the number of apoptotic cells was increased from 3.72% (statistically significant; P < 0.05 in untreated AGS cells to 21.72%, 83.04% and 85.80%, respectively, following treatment with 20, 40, and 60 μmol/L imatinib mesylate. Conclusions: The results suggest that imatinib mesylate can induce apoptosis pathway in a dose-dependent mode and might modulate metastasis by up regulating KAI1 gene expression in human gastric carcinoma AGS cell line.

  19. Inhaled plutonium oxide in dogs

    Anon.

    1981-01-01

    This project is concerned with long-term experiments to determine the life-span dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. The tissue distribution of plutonium, radiation effects in the lung and hematologic changes in plutonium-exposed beagles with lung tumors were evaluated

  20. Respirable versus inhalable dust sampling

    Hondros, J.

    1987-01-01

    The ICRP uses a total inhalable dust figure as the basis of calculations on employee lung dose. This paper was written to look at one aspect of the Olympic Dam dust situation, namely, the inhalable versus respirable fraction of the dust cloud. The results of this study will determine whether it is possible to use respirable dust figures, as obtained during routine monitoring to help in the calculations of employee exposure to internal radioactive contaminants

  1. Inhaled Drug Delivery: A Practical Guide to Prescribing Inhaler Devices

    Pierre Ernst

    1998-01-01

    Full Text Available Direct delivery of medication to the target organ results in a high ratio of local to systemic bioavailability and has made aerosol delivery of respiratory medication the route of choice for the treatment of obstructive lung diseases. The most commonly prescribed device is the pressurized metered dose inhaler (pMDI; its major drawback is the requirement that inspiration and actuation of the device be well coordinated. Other requirements for effective drug delivery include an optimal inspiratory flow, a full inspiration from functional residual capacity and a breath hold of at least 6 s. Available pMDIs are to be gradually phased out due to their use of atmospheric ozone-depleting chlorofluorocarbons (CFCs as propellants. Newer pMDI devices using non-CFC propellants are available; preliminary experience suggests these devices greatly increase systemic bioavailability of inhaled corticosteroids. The newer multidose dry powder inhalation devices (DPIs are breath actuated, thus facilitating coordination with inspiration, and contain fewer ingredients. Furthermore, drug delivery is adequate even at low inspired flows, making their use appropriate in almost all situations. Equivalence of dosing among different devices for inhaled corticosteroids will remain imprecise, requiring the physician to adjust the dose of medication to the lowest dose that provides adequate control of asthma. Asthma education will be needed to instruct patients on the effective use of the numerous inhalation devices available.

  2. Combined derivatization and high-performance liquid chromatography with fluorescence and ultraviolet detection for simultaneous analysis of octreotide and gabexate mesylate metabolite in human pancreatic juice samples.

    Carlucci, Giuseppe; Selvaggi, Federico; Sulpizio, Sara; Bassi, Claudio; Carlucci, Maura; Cotellese, Roberto; Ferrone, Vincenzo; Innocenti, Paolo; Locatelli, Marcello

    2015-06-01

    A simple and sensitive method based on the combination of derivatization and high-performance liquid chromatography with ultraviolet and fluorimetric detection was developed for the simultaneous determination of octreotide and gabexate mesylate metabolite in human pancreatic juice samples. Parameters of the derivatization procedure affecting extraction efficiency were optimized. The developed method was validated according to the International Conference on Harmonization guidelines. The calibration curves were linear over a range of 0.1-15 µg/mL for octreotide and 0.20-15 µg/mL for gabexate mesylate metabolite. Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The limits of detection were 0.025 and 0.05, respectively, for octreotide and gabexate mesylate metabolite. This paper reports the validation of a quantitative high performance liquid chromatography-photodiode array-fluorescence (HPLC-PDA-FL) method for the simultaneous analysis of octreotide and gabexate mesylate metabolite in pancreatic juice by protein precipitation using zinc sulfate-methanol-acetonitrile containing the derivatizing reagent, 4-fluoro-7-nitro-[2,1,3]-benzoxadiazole (NBD-F). Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The method was validated over the concentration ranges 0.1-15 and 0.2-15 µg/mL for octreotide and gabexate mesylate metabolite, respectively, in human pancreatic juice. Biphalin and methyl-p-hydroxybenzoate were used as the internal standards. This method was successfully utilized to support clinical studies in humans. The results from assay validations show that the method is selective, sensitive and robust. The limit

  3. Inhaled plutonium nitrate in dogs

    Dagle, G.E.

    1987-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. They have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 3 tables

  4. Inhaled plutonium nitrate in dogs

    Dagle, G.E.

    1986-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in predicting health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; lymphopenia and neutropenia occurred at the two highest dose levels. The authors have also observed radiation pneumonitis, lung cancer, and bone cancer at the three highest dose levels. 1 figure, 4 tables

  5. Inhaled plutonium nitrate in dogs

    Dagle, G.E.

    1982-01-01

    The major objective of this project is to determine dose-effect relationships of inhaled plutonium nitrate in dogs to aid in the prediction of health effects of accidental exposure in man. For lifespan dose-effect studies, beagle dogs were given a single inhalation exposure to 239 Pu(NO 3 ) 4 , in 1976 and 1977. The earliest biological effect was on the hematopoietic system; as described in previous Annual Reports, lymphopenia and neutropenia occurred at the two highest dose levels. Radiation pneumonitis, lung cancer, and bone cancer have been observed at the highest dose levels

  6. Know How to Use Your Asthma Inhaler

    Full Text Available ... for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma ...

  7. Electrostatic Properties of Particles for Inhalation

    Rowland, Martin

    2015-01-01

    Dry powder inhalers (DPIs) and pressurised metered dose inhalers (pMDIs) aredevices used to deliver therapeutic agents to the lungs. Typically, inhaled activepharmaceutical ingredients (APIs) are electrically resistive materials and are prone toaccumulating electrostatic charge. The build-up of charge on inhaled therapeutics hastraditionally been viewed as a nuisance as it may result in problems such as weighingerrors, agglomeration, adhesion to surfaces and poor flow. Energetic processing st...

  8. Inhalation Injury: State of the Science 2016.

    Foster, Kevin N; Holmes, James H

    This article summarizes research conducted over the last decade in the field of inhalation injury in thermally injured patients. This includes brief summaries of the findings of the 2006 State of the Science meeting with regard to inhalation injury, and of the subsequent 2007 Inhalation Injury Consensus Conference. The reviewed studies are categorized in to five general areas: diagnosis and grading; mechanical ventilation; systemic and inhalation therapy; mechanistic alterations; and outcomes.

  9. Age dependent systemic exposure to inhaled salbutamol

    Bønnelykke, Klaus; Jespersen, Jakob Jessing; Bisgaard, Hans

    2007-01-01

    AIMS: To determine the effect of age on systemic exposure to inhaled salbutamol in children. METHODS: Fifty-eight asthmatic children, aged 3-16 years, inhaled 400 microg of salbutamol from a pressurized metered dose inhaler with spacer. The 20 min serum profile was analyzed. RESULTS: Prescribing...

  10. Know How to Use Your Asthma Inhaler

    Full Text Available ... metered dose inhaler with a spacer [ PDF – 377 KB] Your browser does not support iframes Cómo usar ... inhalador de dosis fija con espaciador [PDF – 343 KB] Using a metered dose inhaler (inhaler in mouth) ...

  11. Estimation of inhalation flow profile using audio-based methods to assess inhaler medication adherence

    Lacalle Muls, Helena; Costello, Richard W.; Reilly, Richard B.

    2018-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) patients are required to inhale forcefully and deeply to receive medication when using a dry powder inhaler (DPI). There is a clinical need to objectively monitor the inhalation flow profile of DPIs in order to remotely monitor patient inhalation technique. Audio-based methods have been previously employed to accurately estimate flow parameters such as the peak inspiratory flow rate of inhalations, however, these methods required multiple calibration inhalation audio recordings. In this study, an audio-based method is presented that accurately estimates inhalation flow profile using only one calibration inhalation audio recording. Twenty healthy participants were asked to perform 15 inhalations through a placebo Ellipta™ DPI at a range of inspiratory flow rates. Inhalation flow signals were recorded using a pneumotachograph spirometer while inhalation audio signals were recorded simultaneously using the Inhaler Compliance Assessment device attached to the inhaler. The acoustic (amplitude) envelope was estimated from each inhalation audio signal. Using only one recording, linear and power law regression models were employed to determine which model best described the relationship between the inhalation acoustic envelope and flow signal. Each model was then employed to estimate the flow signals of the remaining 14 inhalation audio recordings. This process repeated until each of the 15 recordings were employed to calibrate single models while testing on the remaining 14 recordings. It was observed that power law models generated the highest average flow estimation accuracy across all participants (90.89±0.9% for power law models and 76.63±2.38% for linear models). The method also generated sufficient accuracy in estimating inhalation parameters such as peak inspiratory flow rate and inspiratory capacity within the presence of noise. Estimating inhaler inhalation flow profiles using audio based methods may be

  12. Passive inhalation of cannabis smoke

    Law, B; Mason, P A; Moffat, A C; King, L J; Marks, V

    1984-09-01

    Six volunteers each smoked simultaneously, in a small unventilated room (volume 27 950 liter), a cannabis cigarette containing 17.1 mg delta 9-tetrahydrocannabinol (THC). A further four subjects - passive inhalers - remained in the room during smoking and afterwards for a total of 3 h. Blood and urine samples were taken from all ten subjects and analyzed by radioimmunoassay for THC metabolites. The blood samples from the passive subjects taken up to 3 h after the start of exposure to cannabis smoke showed a complete absence of cannabinoids. In contrast, their urine samples taken up to 6 h after exposure showed significant concentrations of cannabinoid metabolites (less than or equal to 6.8 ng ml-1). These data, taken with the results of other workers, show passive inhalation of cannabis smoke to be possible. These results have important implications for forensic toxicologists who are frequently called upon to interpret cannabinoid levels in body fluids.

  13. Inhaled plutonium oxide in dogs

    Park, J.F.

    1982-01-01

    This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for lifespan dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary-fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12μCi. Nineteen of the dogs exposed to 238 Pu haved died during the first 7-1/2 yr after exposure due to bone and/or lung tumors; their body burdens at death ranged from 0.7 to 10μCi. Chronic lymphopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2

  14. Two 238Pu inhalation incidents

    Fleming, R.R.; Hall, R.M.

    1978-06-01

    Two employees inhaled significant amounts of 238 Pu in separate unrelated contamination incidents in 1977. Both acute exposure incidents are described and the urine, feces, and in-vivo chest count data for each employee. Case B ( 238 PuNO 3 ) received 24 DTPA treatments beginning the day of the incident while, for medical reasons, Case A ( 238 PuO 2 ) received no therapy

  15. Inhaled plutonium oxide in dogs

    Park, J.F.

    1985-01-01

    This project is concerned with long-term experiments to determine the lifespan dose-effect relationships of inhaled 239 PuO 2 and 238 PuO 2 in beagles. The data will be used to estimate the health effects of inhaled transuranics. Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols to obtain graded levels of initial lung burdens are being observed for lifespan dose-effect relationships. Mortality due to radiation pneumonitis and lung tumor increased in the four highest dose-level groups exposed to 239 PuO 2 , during the 13-yr postexposure period. During the 10 1/2 years after exposure to 238 PuO 2 , mortality due to lung and/or bone tumors increased in the three highest dose-level groups. Chronic lymphopenia, occurring 0.5 to 2 year after exposure, was the earliest observed effect after inhalation of either 239 PuO 2 or 238 PuO 2 in the four highest dose-level groups that had initial lung burdens greater than or equal to 80 nCi. 3 figures, 6 tables

  16. Cancer hazard from inhaled plutonium

    Gofman, J.W.

    1975-01-01

    The best estimate of the lung cancer potential in humans for inhaled insoluble compounds of plutonium (such as PuO 2 particles) has been grossly underestimated by such authoritative bodies as the International Commission on Radiological Protection and the British Medical Research Council. Calculations are presented of lung cancer induction by 239 Pu as insoluble particles and for deposited reactor-grade Pu. The reason for the gross underestimate of the carcinogenic effects of Pu by ICRP or the British Medical Research Council (BMRC) is their use of a totally unrealistic idealized model for the clearance of deposited Pu from the lungs and bronchi plus their non-recognition of the bronchi as the true site for most human lung cancers. The erroneous model used by such organizations also fails totally to take into account the effect of cigarette-smoking upon the physiological function of human lungs. Plutonium nuclides, such as 239 Pu, or other alpha particle-emitting nuclides, in an insoluble form represent an inhalation cancer hazard in a class some 100,000 times more potent than the potent chemical carcinogens, weight for weight. The already-existing lung cancer data for beagle dogs inhaling insoluble PuO 2 particles is clearly in order of magnitude agreement with calculations for humans

  17. Evaluating complications of local anesthesia administration and reversal with phentolamine mesylate in a portable pediatric dental clinic.

    Boynes, Sean G; Riley, Amah E; Milbee, Sarah; Bastin, Meghan R; Price, Maylyn E; Ladson, Andrea

    2013-08-01

    This study sought to identify and quantify complications with local anesthetic administration and reversal on consecutive patients seen for comprehensive dental care in a school-based, portable dental clinic, and includes data on the patients seen by the participating portable dental providers. In 923 dental visits where local anesthetic was administered, a standardized form was used to gain further information and identify any complications; this was accompanied by a questionnaire for the student's teacher, in order to quantify the student's distraction and disruption ratings following the dental visit. After statistical analysis of the 923 consecutive cases, the overall complication rate was 5.3%. All of the complications were considered to be mild or moderate, and there were no severe event reports. The complications encountered most frequently (n = 49) were associated with self-inflicted soft tissue injury. The results of this study indicate that comprehensive care with local anesthesia delivered by a school-based portable dental clinic has a low risk of complications. Whereas safe administration of dental care is achievable with or without phentolamine mesylate as a local anesthetic reversal agent, its use was determined to improve safety outcomes. Three factors appeared to directly increase the incidence of complications: the administration of an inferior alveolar nerve block, attention deficit disorder, and obesity. Teacher evaluations demonstrated that children receiving care by a portable dental team were able to reorient back to classwork and were not disruptive to classmates.

  18. Thermodynamic solution properties of pefloxacin mesylate and its interactions with organized assemblies of anionic surfactant, sodium dodecyl sulphate

    Usman, Muhammad; Rashid, Muhammad Abid; Mansha, Asim; Siddiq, Mohammad

    2013-01-01

    Graphical abstract: - Highlights: • Free energy of adsorption is more negative than free energy of micellization. • Micellization becomes more spontaneous at high temperature. • There is strong interaction between PFM and SDS. - Abstract: This manuscript reports the physicochemical behavior of antibiotic amphiphilic drug pefloxacin mesylate (PFM) and its interaction with anionic surfactant, sodium dodecyl sulfate (SDS). The data of surface tension and electrical conductivity are helpful to detect the CMC as well as to calculate surface parameters, i.e. surface pressure, π, surface excess concentration, Γ, area per molecule of drug and standard Gibbs free energy of adsorption, ΔG ads and thermodynamic parameters like standard free energy of micellization, ΔG m , standard enthalpy of micellization, ΔH m and standard entropy of micellization, ΔS m . The interaction of this drug with anionic surfactant, sodium dodecyl sulfate (SDS) was studied by electrical conductivity and UV/visible spectroscopy. This enabled us to compute the values of partition coefficient (K x ), free energy of partition, ΔG p , binding constant, K b , free energy of binding, ΔG b , number of drug molecules per micelle, n, and thermodynamic parameters of drug–surfactant interaction

  19. Measurement and prediction of dabigatran etexilate mesylate Form II solubility in mono-solvents and mixed solvents

    Xiao, Yan; Wang, Jingkang; Wang, Ting; Ouyang, Jinbo; Huang, Xin; Hao, Hongxun; Bao, Ying; Fang, Wen; Yin, Qiuxiang

    2016-01-01

    Highlights: • Solubility of DEM Form II in mono-solvents and binary solvent mixtures was measured. • Regressed UNIFAC model was used to predict the solubility in solvent mixtures. • The experimental solubility data were correlated by different models. - Abstract: UV spectrometer method was used to measure the solubility data of dabigatran etexilate mesylate (DEM) Form II in five mono-solvents (methanol, ethanol, ethane-1,2-diol, DMF, DMAC) and binary solvent mixtures of methanol and ethanol in the temperature range from 287.37 K to 323.39 K. The experimental solubility data in mono-solvents were correlated with modified Apelblat equation, van’t Hoff equation and λh equation. GSM model and Modified Jouyban-Acree model were employed to correlate the solubility data in mixed solvent systems. And Regressed UNIFAC model was used to predict the solubility of DEM Form II in the binary solvent mixtures. Results showed that the predicted data were consistent with the experimental data.

  20. Spectrofluorimetric determination of gemifloxacin mesylate and linezolid in pharmaceutical formulations: Application of quinone-based fluorophores and enhanced native fluorescence

    Moussa Bahia Abbas

    2014-03-01

    Full Text Available Quinone-based fluorophores and enhanced native fluorescence techniques were applied for a fast quantitative analysis of gemifloxacin mesylate (GEM and linezolid (LIN in pharmaceutical formulations. For this purpose, three sensitive, accurate and precise spectrofluorimetric methods were developed. GEM, as an n-electron donor, reacts with 7,7,8,8-tetracyanoquinodimethane (method A and 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (method B as п-electron acceptors, forming charge transfer complexes that exhibit high fluorescence intensity at 441 and 390 nm upon excitation at 260 and 339 nm, respectively. Method C depends on measurement of enhanced native fluorescence of LIN in phosphate buffer (pH 5 at 380 nm upon excitation at 260 nm. Experimental factors affecting fluorescence intensity were optimized. Linearity was obtained over concentration ranges 50-500, 10-60 and 20-400 ng mL-1 for methods A, B and C, respectively. The developed methods were validated and successfully applied for determination of the cited drugs in tablets.

  1. Electroanalytical Determination of Gemifloxacin Mesylate in Bulk, Tablets and Human Urine Using Gold Nanoparticles Modified Carbon Paste Electrode

    Ali Attia

    2014-12-01

    Full Text Available A simple, precise, inexpensive and sensitive voltammetric method has been developed for the determination of gemifloxacin mesylate (GEM in the presence of tween 80 in the bulk, farmaceutical dosage forms and human urine at gold nanoparticles modified carbon paste electrode (GNCPE. The electrochemical behavior of GEM has been investigated by using cyclic voltammetry (CV and differential pulse voltammetry (DPV techniques. The electrochemical oxidation of GEM was an irreversible process which exhibited adsorption-diffusion controlled process behavior in Britton-Robinson (BR buffer over the entire pH range of values from 2 to 9. The adsorptive stripping response was evaluated as a function of some variables such as pH, type of surfactant, scan rate and accumulation time. The anodic peak current varied linearly over the range from 8.0 × 10-7 to 2.8 × 10-5 M. The limits of detection and quantification were 7.32 × 10-8 M and 2.44 × 10-7 M, respectively. The relative standard deviations and the percentage recoveries were found in the following ranges: 0.58-1.35% and 99.37-101.76%, respectively.

  2. How to use an inhaler - no spacer

    ... MDI) administration - no spacer; Bronchial nebulizer; Wheezing - nebulizer; Reactive airway - nebulizer; COPD - ... 66. National Asthma Education and Prevention Program website. How to use a metered-dose inhaler. ...

  3. Know How to Use Your Asthma Inhaler

    Full Text Available ... on Spirometry Parents Preventing and Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ...

  4. Inhaled ciclesonide versus inhaled budesonide or inhaled beclomethasone or inhaled fluticasone for chronic asthma in adults: a systematic review

    Halpin David MG

    2006-06-01

    Full Text Available Abstract Background Ciclesonide is a new inhaled corticosteroids licensed for the prophylactic treatment of persistent asthma in adults. Currently beclomethasone dipropionate, budesonide and fluticasone propionate are the most commonly prescribed inhaled corticosteroids for the treatment of asthma but there has been no systematic review comparing the effectiveness and safety ciclesonide to these agents. We therefore aimed to systematically review published randomised controlled trials of the effectiveness and safety of ciclesonide compared to alternative inhaled corticosteroids in people with asthma. Methods We performed literature searches on MEDLINE, EMBASE, PUBMED, the COCHRANE LIBRARY and various Internet evidence sources for randomised controlled trials or systematic reviews comparing ciclesonide to beclomethasone or budesonide or fluticasone in adult humans with persistent asthma. Data was extracted by one reviewer. Results Five studies met the inclusion criteria. Methodological quality was variable. There were no trials comparing ciclesonide to beclomethasone. There was no significant difference between ciclesonide and budesonide or fluticasone on the following outcomes: lung function, symptoms, quality of life, airway responsiveness to a provoking agent or inflammatory markers. However, the trials were very small in size, increasing the possibility of a type II error. One trial demonstrated that the combined deposition of ciclesonide (and its active metabolite in the oropharynx was 47% of that of budesonide while another trial demonstrated that the combined deposition of ciclesonide (and its active metabolite in the oropharynx was 53% of that of fluticasone. One trial demonstrated less suppression of cortisol in overnight urine collection after ciclesonide compared to fluticasone (geometric mean fold difference = 1.5, P Conclusion There is very little evidence comparing CIC to other ICS, restricted to very small, phase II studies of low

  5. Chronic myeloid leukemia: an overview of the determinants of effectiveness and therapeutic response in the first decade of treatment with imatinib mesylate in a Brazilian hospital

    Danielle Maria Camelo Cid

    2013-01-01

    Full Text Available Background: In the last decade, there has been a revolution in chronic myeloid leukemia treatment with the introduction of tyrosine kinase inhibitors with imatinib mesylate becoming the frontline therapy. Objective: To evaluate the therapeutic efficacy of imatinib mesylate in treating chronic myeloid leukemia patients and to identify factors related to therapeutic efficacy. Methods: This retrospective study was based on information obtained from patients'records in the Hematology Service of Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará (HUWC / UFC. All patients diagnosed with chronic myeloid leukemia that took imatinib mesylate for a minimum of 12 months in the period from January 2001 to January 2011 were included. From a population of 160 patients, 100 were eligible for analysis. Results: The study population consisted of 100 patients who were mostly male (51% with ages rangingbetween 21 and 40 years (42%, from the countryside (59%, in the chronic phase (95%, with high-riskprognostic factors (40%; the prognosis of high risk was not associated with complete hematologic responseor complete cytogenetic response, but correlated to complete molecular response or major molecularresponse. Reticulin condensation was associated with complete hematologic response and completecytogenetic response. It was found that 53% of patients had greater than 90% adherence to treatment. Thehigh adherence was correlated to attaining complete cytogenetic response in less than 12 months. Moreover,20% of patients had good response. Conclusion: Significant changes are indispensable in the monitoring of patients with chronic myeloid leukemia. Thus, the multidisciplinary team is important as it provides access to the full treatment and not just to medications.

  6. Experimental study of inhalation injury

    Hamamoto, Junji; Ohura, Takehiko; Yoshida, Tetsunori; Ono, Ichiro; Iida, Kazunori; Ooiwa, Akira

    1984-01-01

    We conducted the following inhalation injury experiment on dogs. A hose was connected to the chimney of a stove so that wood smoke could be led to the dog by means of damper adjustment. Under intravenous anesthesia, the dog was intubated and made to inhale the wood smoke for from 5 to 10 minutes at a smoke temperature of between 55 and 60 C. After this inhalation, observation of trachea by a fiberoptic bronchoscopy was done and blood gas change, blood analysis, serum electrolytes and cardiac output were observed with a passage of time. Furthermore, we did lung scan using 133xe and performed autopsies. We injected 0.3 microcurie of 133Xe per 1 kg body weight in its vein of the dog's foreleg. The concentration in the lung reached maximum 20 seconds after the injection and then washed out with expiration. In the control experiment with a normal dog, it was almost all washed out 70 seconds after the 133Xe injection. But the delay of wash out time was observed in smoke inhaled dogs. In other words it can be said that the wash out time was dependent on the degree of injury. When these data were processed by a computer, and exponential approximation decay curve was obtained. Then these data were replotted into semi-logarithmic chart and a linear line was obtained. One may interprete the clearance rate recorded on the graph as the ability of the lung to wash out 133Xe, that is, the degree of injury of the lung. The clearance rate had a tendancy to concentrate between 3.5 to 5.0 when observed 2 to 7 hours after the injury. However when observed 20 to 27 hours, concentration was between 2.4 to 3.2. Furthermore, the clearance rate for each lung regions were obtained and compared with one another by means of proper computer program. The clearance rate had lower values at lower region of lung, that is, deterioration of lung function was greater. (J.P.N.)

  7. Preparation of 14C-labeled 8,9-didehydro-6,8-dimethyl-2-methylthioergoline mesylate, a dopamine antagonist potentially useful in the treatment of schizophrenia

    Wheeler, W.J.

    1988-01-01

    We have prepared 14 C-labeled 8,9-didehydro-6,8-dimethyl-2-methyl-thioergoline mesylate (LY 170542), a dopamine antagonist potentially useful as an anti-psychotic. The 14 C-label was introduced via a novel application of the Wittig reaction on 1-(4'-toluene-sulfonyl)-8,9-didehydro-6-methyl-ergolin-8-one and subsequent reduction of 1-(4'-toluenesulfonyl)-17-[ 14 C]-lysergene by lithium/ammonia at -33 0 C. The 17-[ 14 C]-agroclavine thus prepared was converted into 17-[ 14 C]-LY 170542 by reaction with methanesulfenyl chloride/methanesulfonic acid. (author)

  8. Subcellular distribution of [3H]-dexamethasone mesylate binding sites in Leydig cells using electron microscope radioautography

    Stalker, A.; Hermo, L.; Antakly, T.

    1991-01-01

    The present view is that glucocorticoid hormones bind to their cytoplasmic receptors before reaching their nuclear target sites, which include specific DNA sequences. Although it is believed that cytoplasmic sequestration of steroid receptors and other transcription factors (such as NFKB) may regulate the overall activity of these factors, there is little information on the exact subcellular sites of steroid receptors or even of any other transcription factors. Tritiated (3H)-dexamethasone 21-mesylate (DM) is an affinity label that binds covalently to the glucocorticoid receptor (GR), thereby allowing morphological localization of the receptor at the light and electron microscope levels as well as for quantitative radioautographic (RAG) analysis. After injection of 3H-DM into the testis, a specific radioautographic signal was observed in Leydig cells, which correlated with a high level of immunocytochemically demonstrable GR in these cells at the light-microscope level. To localize the 3H-DM binding sites at the electron microscope (EM) level, the testes of 5 experimental and 3 control adrenalectomized rats were injected directly with 20 microCi 3H-DM; control rats received simultaneously a 25-fold excess of unlabeled dexamethasone; 15 min later, rats were fixed with glutaraldehyde and the tissue was processed for EM RAG analysis combined with quantitative morphometry. The radioautographs showed that the cytosol, nucleus, smooth endoplasmic reticulum (sER), and mitochondria were labeled. Since the cytosol was always adjacent to tubules of the sER, the term sER-rich cytosol was used to represent label over sER networks, which may also represent cytosol labeling due to the limited resolution of the radioautographic technique. Labeling was highest in sER-rich cytosol and mitochondria, at 53% and 31% of the total, respectively

  9. Maximizing the Therapeutic Efficacy of Imatinib Mesylate-Loaded Niosomes on Human Colon Adenocarcinoma Using Box-Behnken Design.

    Kassem, Mohammed A; El-Sawy, Hossam S; Abd-Allah, Fathy I; Abdelghany, Tamer M; El-Say, Khalid M

    2017-01-01

    This research purposed to formulate an optimized imatinib mesylate (IM)-loaded niosomes to improve its chemotherapeutic efficacy. The influence of 3 formulation factors on niosomal vesicular size (Y 1 ), zeta potential (Y 2 ), entrapment capacity percentage (Y 3 ), the percentage of initial drug release after 2 h (Y 4 ), and the percentage of cumulative drug release after 24 h (Y 5 ) were studied and optimized using Box-Behnken design. Optimum desirability was specified and the optimized formula was prepared, stability tested, morphologically examined, checked for vesicular bilayer formation and evaluated for its in vitro cytotoxicity on 3 different cancer cell lines namely MCF-7, HCT-116, and HepG-2 in addition to 1 normal cell line to ensure its selectivity against cancer cells. The actual responses of the optimized IM formulation were 425.36 nm, -62.4 mV, 82.96%, 18.93%, and 89.45% for Y 1 , Y 2 , Y 3 , Y 4 , and Y 5 , respectively. The optimized IM-loaded niosomes confirmed the spherical vesicular shape imaged by both light and electron microscopes and further proven by differential scanning calorimetry. Moreover, the optimized formula exhibited improved stability on storage at 4 ± 2°C and superior efficacy on MCF7, HCT-116, and HepG2 as IC 50 values were 6.7, 16.4, and 7.3 folds less than those of free drug, respectively. Interestingly, IC 50 of the optimized formula against normal cell line was ranged from 3 to 11 folds higher than in different cancer cells indicating a higher selectivity of the optimized formula to cancer cells. In conclusion, the incorporation of IM in niosomes enhanced its efficacy and selectivity toward cancer cells, presenting a promising tool to fight cancer using this approach. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  10. The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice.

    Laurent L Reber

    Full Text Available Gouty arthritis is caused by the deposition of monosodium urate (MSU crystals in joints. Despite many treatment options for gout, there is a substantial need for alternative treatments for patients unresponsive to current therapies. Tyrosine kinase inhibitors have demonstrated therapeutic benefit in experimental models of antibody-dependent arthritis and in rheumatoid arthritis in humans, but to date, the potential effects of such inhibitors on gouty arthritis has not been evaluated. Here we demonstrate that treatment with the tyrosine kinase inhibitor imatinib mesylate (imatinib can suppress inflammation induced by injection of MSU crystals into subcutaneous air pouches or into the ankle joint of wild type mice. Moreover, imatinib treatment also largely abolished the lower levels of inflammation which developed in IL-1R1-/- or KitW-sh/W-sh mice, indicating that this drug can inhibit IL-1-independent pathways, as well as mast cell-independent pathways, contributing to pathology in this model. Imatinib treatment not only prevented ankle swelling and synovial inflammation when administered before MSU crystals but also diminished these features when administrated after the injection of MSU crystals, a therapeutic protocol more closely mimicking the clinical situation in which treatment occurs after the development of an acute gout flare. Finally, we also assessed the efficiency of local intra-articular injections of imatinib-loaded poly(lactic-co-glycolic acid (PLGA nanoparticles in this model of acute gout. Treatment with low doses of this long-acting imatinib:PLGA formulation was able to reduce ankle swelling in a therapeutic protocol. Altogether, these results raise the possibility that tyrosine kinase inhibitors might have utility in the treatment of acute gout in humans.

  11. Inhalants

    ... most commonly abuse glue, shoe polish, spray paints, gasoline, and lighter fluid. New users ages 16–17 ... paint thinners or removers, degreasers, dry- cleaning fluids, gasoline, and lighter fluid  Art or office supply solvents , ...

  12. Inhalants

    ... Viral) HIV/AIDS Mental Health Military Opioid Overdose Reversal with Naloxone (Narcan, Evzio) Pain Prevention Recovery Substance ... chest pain, are misused in order to improve sexual pleasure by expanding and relaxing blood vessels. What ...

  13. Potential consequences of yellowcake inhalation

    Eidson, A.F.; Damon, E.G.; Hahn, F.F.; Pickrell, J.A.; Muggenburg, B.A.

    1988-01-01

    The uranium ore milling process includes dusty operations and workers can be exposed to aerosols of highly concentrated uranium. Measurements made during uranium milling operations were used to predict that, if a worker was not wearing respiratory protection, 0.14-50 μg U/min might be deposited in the respiratory tract, predominantly in the nesopharyngeal compartment. Yellowcake was shown by infrared and solubility measurements to be a highly variable mixture of ammonium diuranate and U 3 O 8 . Biokinetic studies of inhaled yellowcake in beagle dogs showed that the more soluble fraction caused kidney damage. After inhalation of 0.5 mg U/kg body wt of soluble uranium, kidney concentration was 0.3 to 3.5 μg U/g kidney within 4-8 days; and was accompanied by kidney damage. Kidney damage was neither severe nor widespread, and was repaired within 64 days after exposure. The damage seen is due to heavy metal nephrotoxicity of uranium, and not to radiation damage

  14. Inhaler devices - from theory to practice

    Sanchis, Joaquin; Corrigan, Chris; Levy, Mark L

    2013-01-01

    This brief overview of the factors determining lung deposition of aerosols provides background information required by health care providers when instructing patients to use their prescribed inhalers. We discuss differences in the optimal inhalation manoeuvres for each type of aerosol generator a...

  15. Toxicological perspectives of inhaled therapeutics and nanoparticles.

    Hayes, Amanda J; Bakand, Shahnaz

    2014-07-01

    The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

  16. Inhalant Dependence and its Medical Consequences

    Mehmet Hamid Boztaş

    2010-12-01

    Full Text Available The term of inhalants is used for matters easily vapors. Inhalants are preferred for rapid, positive reinforcement and mild high effects. Products including inhalants are cheap, accessible, legal substances and are prevalently used in community. The prevalence of inhalant use in secondary schools in Turkey is about 5.1%. Inhalant substance dependence is generally observed within 14-15 age group. Age at first use could be as low as 5 to 6 years of age. Substance dependence is more probable in adults working in substance existing places. Inhalant usage is common in disadvantaged groups, children living in street, people with history of crimes, prison, depression, suicide, antisocial attitudes and conflict of family, history of abuse, violence and any other drug dependence and isolated populations. Inhalants are absorbed from lungs, after performing their quick and short effect metabolized by cytochrom P450 enzyme system except inhalant nitrites group which has a depressing effect like alcohol. In chronic use general atrophy, ventricular dilatation and wide sulcus were shown in cerebrum, cerebellum and pons by monitoring brain. Defects are mostly in periventricular, subcortical regions and in white matter. Demyelinization, hyperintensity, callosal slimming and wearing off in white and gray matter margins was also found. Ravages of brain shown by brain monitorisation are more and serious in inhalant dependence than in other dependences. It is important to decrease use of inhalants. Different approaches should be used for subcultures and groups in prevention. Prohibiting all the matters including inhalant is not practical as there are too many substances including inhalants. Etiquettes showing harmful materials can be used but this approach can also lead the children and adolescents recognize these substances easily.. Despite determintal effects of inhalant dependence, there are not yet sufficient number of studies conducted on prevention and

  17. Falla cardiaca asociada con el uso de imatinib mesilato: Reporte de un caso Heart failure associated to imatinib mesylate use: Case report

    Clara Saldarriaga

    2008-12-01

    Full Text Available La cardiotoxicidad por medicamentos es un evento cada vez más frecuente en la práctica clínica diaria. Inhibidores de la proteína de fusión Brc/Abl como el imatinib mesilato, son una nueva herramienta para el tratamiento de algunas neoplasias hematológicas, en especial de la leucemia mieloide crónica. Sin embargo, en la literatura se reporta desarrollo de cardiotoxicidad a causa de este medicamento. Se presenta el caso de una mujer joven con corazón de estructura sana quien desarrolla cardiotoxicidad por imatinib pocas semanas después de iniciarlo.Cardiotoxicity due to drugs has become a frequent event in the daily clinical practice. Fusion protein Brc/Abl inhibitors such as imatinib mesylate constitute a new tool for the treatment of some hematogical neoplasias, especially chronic myeloid leukemia. Nevertheless, there have been reports in the literature regarding imatinib mesylate toxicity. We present the case of a young woman with a structurally healthy heart who developed cardiotoxicity with imatinib few weeks after its initiation.

  18. Simultaneous regression of Philadelphia chromosome and multiple nonrecurrent clonal chromosomal abnormalities with imatinib mesylate in a patient autografted 22 years before for chronic myelogenous leukemia.

    Van Den Akker, J; Coppo, P; Portnoï, M F; Barbu, V; Bories, D; Gorin, N C

    2007-09-01

    A 31-year-old patient developed chronic myelogenous leukemia (CML) in November, 1983. In November 1984, following a diagnosis of acceleration, he received an autologous hemopoietic transplant after conditioning with cyclophosphamide and total body irradiation. The autologous marrow was purged with mafosfamide. Over 20 years, the patient remained in chronic phase of CML. Multiple nonrecurrent clonal chromosomal abnormalities appeared leading to a very complex karyotype, including among others involvement of chromosomes 1, 7, 9, 13, 19, and X. Fluorescent in situ hybridization showed that the two chromosomes 9 were involved. Acute myeloid crisis was diagnosed in February, 2004. Treatment with imatinib mesylate resulted within 6 months in a total disappearance of all chromosomal abnormalities with a complete cytogenetic and molecular response, which persists 3 years later. We question whether the ex vivo purging procedure with mafosfamide has favored the occurrence of these particular cytogenetic abnormalities (with no independent oncogenic potential) within the original leukemic stem cell pool. It remains unclear whether the autologous transplantation has indeed resulted into some prolongation of the duration of the chronic phase, which lasted for 20 years. At time of acute crisis, the dramatic response to imatinib mesylate leading to a complete cytogenetic and molecular response is noteworthy.

  19. Reactive Periostitis from Inhalant Abuse.

    Hock, Lauren E; Honkanen, Iiro; Fiordellisi, Wendy; Bettendorf, Brittany

    2018-04-16

    The patient, a 36-year-old woman, presented with a 6-week history of swollen hands and fingers and associated arthralgia. She had a history of polysubstance abuse. The arthralgia and swelling started one month after she began inhaling two cans of "Dust-Off" (1,1-difluoroethane) daily. Physical examination revealed tender proximal and middle phalanges of all fingers bilaterally with bulbous appearance (A). There was no clubbing. Radiography of the hands revealed diffuse reactive periostitis with discrete layering of periosteal bone formation without bony destruction (B). TSH was normal. Serum alkaline phosphatase was 854 U/L. Computed tomography of the chest, abdomen, and pelvis showed no evidence of malignancy or pulmonary disease This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. [Methemoglobinemia after inhalation of poppers].

    Janssens, U; Hillen, S; Janssens, T; Grafe, J

    2018-04-17

    This case report presents a case of symptomatic methemoglobinemia (MetHb 31.6%) after inhalation of volatile nitrites (poppers). The patient's medical history and symptoms are discussed together with pathophysiology of methemoglobinemia, diagnostics, and antidote therapy. Pulse oxymetry, arterial blood gas analysis, and CO-oximetry receive particular attention as well as antidote therapy with methylene blue. The patient was treated successfully with intravenous methylene blue. Within 60 min methemoglobinemia returned to normal values (MetHb 0.6%). Stimulating compounds such as volatile nitrites (poppers) may lead to potentially fatal methemoglobinemia. Swift and accurate diagnosis and targeted therapy with methylene blue can lead to rapid recovery.

  1. Inhaled actinides: some safety issues and some research problems

    Bair, W.J.

    1978-01-01

    The following topics are discussed: limited research funds; risk coefficients for inhaled particles; the hot particle hypothesis; the Gofman-Martell contention; critical tissues for inhaled actinides inhalation hazards associated with future nuclear fuel cycles; and approach to be used by the inhalation panel

  2. Know How to Use Your Asthma Inhaler

    Full Text Available ... Evaluation Roadblocks 1A. Focus On: Walking Through the Steps and Standards 2. Getting Started 3. Describing and ... to use your metered dose inhaler. Print the step-by-step instructions and keep them with your ...

  3. Know How to Use Your Asthma Inhaler

    Full Text Available ... on this page will be unavailable. For more information about this message, please visit this page: About CDC.gov . ... Asthma Action Plan Flu Shots Inhalers Data, Statistics, ...

  4. Know How to Use Your Asthma Inhaler

    Full Text Available ... Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, and Surveillance Most ... control over their asthma. Quick Links Asthma Action Plan America Breathing Easier [PDF – 1.1 MB] ASL ...

  5. Know How to Use Your Asthma Inhaler

    Full Text Available ... Brochures Facts Guidance on Spirometry Parents Preventing and Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ...

  6. Know How to Use Your Asthma Inhaler

    Full Text Available ... How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma ... RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton Road ...

  7. Know How to Use Your Asthma Inhaler

    Full Text Available ... Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma and avoid an attack by ... you to do and by avoiding things that can cause an attack. Watch a video to follow ...

  8. Know How to Use Your Asthma Inhaler

    Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... Case Studies Open Airways for Schools Asthma Care Training Wee Wheezers Adventures of Puff Inner City Asthma ...

  9. Know How to Use Your Asthma Inhaler

    Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act ...

  10. Know How to Use Your Asthma Inhaler

    Full Text Available ... In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, and Surveillance Most Recent ... AsthmaStats Asthma as the Underlying Cause of Death Flu Vaccination among Adults with Current Asthma Flu Vaccination ...

  11. Health risks associated with inhaled nasal toxicants

    Feron, VJ; Arts, JHE; Kuper, CF; Slootweg, PJ; Woutersen, RA

    2001-01-01

    Health risks of inhaled nasal toxicants were reviewed with emphasis on chemically induced nasal lesions in humans, sensory irritation, olfactory and trigeminal nerve toxicity, nasal immunopathology and carcinogenesis, nasal responses to chemical mixtures, in vitro models, and nasal dosimetry- and

  12. Know How to Use Your Asthma Inhaler

    Full Text Available ... for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers Data, Statistics, ... Mixed Methods 5. Purpose Informs Design Other Evaluation Resources Multimedia ... USA.gov TOP

  13. Know How to Use Your Asthma Inhaler

    Full Text Available ... Asthma & Community Health Know How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma and avoid an attack by taking your medicine ...

  14. Know How to Use Your Asthma Inhaler

    Full Text Available ... and Publications Related Articles, Publications, and Links Asthma’s Impact on the Nation Fact Sheet State Data Profiles ( ... How to Use Your Asthma Inhaler Recommend on Facebook Tweet Share Compartir You can control your asthma ...

  15. [INHALED ANTIBIOTICS IN TREATMENT OF NOSOCOMIAL PNEUMONIA].

    Kuzovlev, A N; Moroz, V V; Golubev, A M

    2015-01-01

    Nosocomial pneumonia is the most common infection in intensive care units. Currently the problem of resistance of noso-comial pathogens to miost of antibiotics is crucial. Using of inhaled antibiotics in combination with intravenous drugs is eff ective and safe method for treatment of nosocomial pneumonia. The literature review describes current opportunities of ihhaled antibiotic therapy of nosocomial pneumonia, descriptions of drugs, the advantages and disadvantages of this treatment. Special attention is paid for using inhaled aminoglycosides for nosocomial pneumonia.

  16. Intestinal circulation during inhalation anesthesia

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86 Rb and 9-microns spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO 2 ) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines

  17. Prolonged treatment with imatinib mesylate in patients with advanced chronic myeloid leukemia causes a reduction of bcr/abl mRNA levels independent of cytogenetic response.

    Cariani, E; Capucci, M; Micheletti, M; Spalenza, F; Zanella, I; Albertini, A; Rossi, G

    2003-06-01

    Bcr/abl mRNA levels were monitored in 13 patients with chronic myeloid leukemia receiving imatinib mesylate over a period of 78 weeks. During treatment median bcr/abl mRNA levels progressively declined from 77.2 normalized dose (nD) at baseline to 11.28 nD after 13 weeks ( P<0.05) and to 1.28 nD after 78 weeks ( P<0.05). After 13 weeks, bcr/abl mRNA levels were significantly lower in cytogenetic responders compared to nonresponders ( P<0.05), but subsequent decrease in the transcript levels caused the loss of any correlation to the cytogenetic status. These results suggest that bcr/abl mRNA levels may reflect cytogenetic response only during the early phases of imatinib therapy.

  18. [Disappearance of a Philadelphia chromosome-positive clone and appearance of a -negative clone following treatment with imatinib mesylate in acute myelomonocytic leukemia].

    Takahashi, Wataru; Arai, Yukihiro; Tadokoro, Jiro; Takeuchi, Kengo; Yamagata, Tetsuya; Mitani, Kinuko

    2006-02-01

    A 63-year-old female was diagnosed as having Philadelphia chromosome-positive acute myelomonocytic leukemia in June 2002. The patient received monotherapy with imatinib mesylate or combination therapy with DCM and idarubicin/cytarabine, both of which failed in attaining disease remission. However, the second imatinib administration plus CAG therapy resulted in disappearance of the Philadelphia chromosome-positive clone and increase of Philadelphia chromosome-negative cells. During a therapy-withholding period due to fungal infection, the Philadelphia chromosome-positive clone expanded and the patient died of cerebral hemorrhage in February 2003. The transient suppression of the Philadelphia chromosome-positive clone may have brought about amplification of the Philadelphia chromosome-negative cells after the secondary imatinib treatment.

  19. Assessing inhalation injury in the emergency room

    Tanizaki S

    2015-07-01

    Full Text Available Shinsuke Tanizaki Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Japan Abstract: Respiratory tract injuries caused by inhalation of smoke or chemical products are related to significant morbidity and mortality. While many strategies have been built up to manage cutaneous burn injuries, few logical diagnostic strategies for patients with inhalation injuries exist and almost all treatment is supportive. The goals of initial management are to ensure that the airway allows adequate oxygenation and ventilation and to avoid ventilator-induced lung injury and substances that may complicate subsequent care. Intubation should be considered if any of the following signs exist: respiratory distress, stridor, hypoventilation, use of accessory respiratory muscles, blistering or edema of the oropharynx, or deep burns to the face or neck. Any patients suspected to have inhalation injuries should receive a high concentration of supplemental oxygen to quickly reverse hypoxia and to displace carbon monoxide from protein binding sites. Management of carbon monoxide and cyanide exposure in smoke inhalation patients remains controversial. Absolute indications for hyperbaric oxygen therapy do not exist because there is a low correlation between carboxyhemoglobin levels and the severity of the clinical state. A cyanide antidote should be administered when cyanide poisoning is clinically suspected. Although an ideal approach for respiratory support of patients with inhalation injuries do not exist, it is important that they are supported using techniques that do not further exacerbate respiratory failure. A well-organized strategy for patients with inhalation injury is critical to reduce morbidity and mortality. Keywords: inhalation injury, burn, carbon monoxide poisoning, cyanide poisoning

  20. Evaluation of the Safety of Imatinib Mesylate in 200 Iraqi Patients with Chronic Myeloid Leukemia in the Chronic Phase: Single-Center Study

    Bassam Francis Matti

    2013-12-01

    Full Text Available OBJECTIVE: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML. During therapy, a few patients may develop hematological and non-hematological adverse effects. METHODS: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day. RESULTS: Two hundred CML patients in chronic phase were included in this study; the male: female ratio was 0.7: 1 with mean age 39.06±13.21 years (ranged from 15-81 years. The study showed that the commonest hematological side effects were grade 2 anemia (12.5% followed by leukopenia (8% and thrombocytopenia (4%, while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%, followed by musculoskeletal pain (35.5%, then gastro-intestinal symptoms (vomiting, diarrhea (19%. Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity. CONCLUSION: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectively.

  1. Inhaled mannitol for cystic fibrosis.

    Nevitt, Sarah J; Thornton, Judith; Murray, Clare S; Dwyer, Tiffany

    2018-02-09

    Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review. To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences.Date of last search: 28 September 2017. All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment. Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE. Six studies (reported in 50 publications) were included with a total of 784 participants.Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were

  2. Inhaled antibiotics for lower airway infections.

    Quon, Bradley S; Goss, Christopher H; Ramsey, Bonnie W

    2014-03-01

    Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

  3. Acute renal failure from inhalation of mycotoxins.

    Di Paolo, N; Guarnieri, A; Loi, F; Sacchi, G; Mangiarotti, A M; Di Paolo, M

    1993-01-01

    Mysterious deaths of archeologists after opening Egyptian tombs have been suspected to be secondary to inhalation of mycotoxin, however, the hypothesis has never been verified. Recently, we observed a case of acute renal failure (ARF) undeniably due to inhalation of ochratoxin of Aspergillus ochraceus. After spending 8 h in a granary which had been closed for several months, a farmer and his wife suffered temporary respiratory distress; 24 h later, the woman developed nonoliguric ARF and biopsy revealed tubulonecrosis which healed in 24 days. Toxic substances were not found, but a strain of A. ochraceus producing ochratoxin was isolated from the wheat.

  4. Inhaled mycotoxins lead to acute renal failure.

    Di Paolo, N; Guarnieri, A; Garosi, G; Sacchi, G; Mangiarotti, A M; Di Paolo, M

    1994-01-01

    Mysterious deaths of archeologists after opening Egyptian tombs have been suspected, but never proved, to be secondary to inhalation of mycotoxin. We observed a case of acute renal failure (ARF) due to inhalation of ochratoxin A produced by a mould of the species Aspergillus ochraceus. After working 8 h in a granary closed for several months, a farmer and his wife suffered respiratory distress; the woman developed non-oliguric ARF and biopsy revealed tubulonecrosis. A strain of Aspergillus ochraceus producing ochratoxin was isolated from the wheat.

  5. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis: A European consensus

    Heijerman, Harry; Westerman, Elsbeth; Conway, Steven

    2009-01-01

    , mucolytics/mucous mobilizers, anti-inflammatory drugs, bronchodilators and combinations of solutions. Additionally, we review the current knowledge on devices for inhalation therapy with regard to optimal particle sizes and characteristics of wet nebulisers, dry powder and metered dose inhalers. Finally, we...... review the current status of inhaled medication in CF, including the mechanisms of action of the various drugs, their modes of administration and indications, their effects on lung function, exacerbation rates, survival and quality of life, as well as side effects. Specifically we address antibiotics...

  6. Cow Dung Ingestion and Inhalation Dependence: A Case Report

    Khairkar, Praveen; Tiple, Prashant; Bang, Govind

    2009-01-01

    Although abuse of several unusual inhalants had been documented, addiction to cow dung fumes or their ashes has not been reported in medical literature as yet. We are reporting a case of cow dung dependence in ingestion and inhalational form.

  7. Social stigma stops adolescents from using inhalers for asthma.

    2017-07-10

    Forgetfulness, poor routines, inadequate inhaler technique, organisational difficulties and families not understanding or accepting their children's asthma are described as barriers to the use of inhalers among adolescents with asthma.

  8. Activities of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro.

    Patick, A K; Boritzki, T J; Bloom, L A

    1997-01-01

    Nelfinavir mesylate (formerly AG1343) is a potent and selective, nonpeptidic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease that was discovered by protein structure-based design methodologies. We evaluated the antiviral and cytotoxic effects of two-drug combinations of nelfinavir with the clinically approved antiretroviral therapeutics zidovudine (ZDV), lamivudine (3TC), dideoxycytidine (ddC; zalcitabine), stavudine (d4T), didanosine (ddI), indinavir, saquinavir, and ritona...

  9. Marrow signal changes observed in follow-up whole-body MRI studies in children and young adults with neurofibromatosis type 1 treated with imatinib mesylate (Gleevec) for plexiform neurofibromas

    Karmazyn, Boaz; Cohen, Mervyn D. [Riley Hospital for Children, Indiana University Health, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN (United States); Jennings, Samuel Gregory [Indiana University School of Medicine, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Robertson, Kent A. [Riley Hospital for Children, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN (United States)

    2012-10-15

    We observed bone marrow signal changes (BMSC) in patients with plexiform neurofibromas after treatment with imatinib mesylate (Gleevec). To evaluate the pattern and natural history of BMSC. The data were obtained from a pilot study of imatinib mesylate in patients with plexiform neurofibromas. All patients underwent baseline and sequential whole-body STIR 1.5-T MRI after treatment. The bone marrow signal on MRI was evaluated for abnormalities, location and pattern, and any change on follow-up studies. The study group included 16 patients (8 males) with a median age of 14 years (range 4 to 25 years). The mean whole-body MRI follow-up duration was 1.9 years. Of the 16 patients, 14 (88%) developed BMSC. The signal change was asymmetrical in 9 of the 14 patients (64%). The appendicular skeleton was involved in all 14 patients and the axial skeleton in 3 patients (21%). BMSC was followed in 13 patients and decreased signal was seen in 9 patients (69%) after a mean duration of 1.3 years of treatment (range 0.6 to 2.9 years); no complications were observed. BMSC appeared in most patients with neurofibromatosis type 1 following treatment with imatinib mesylate. BMSC was unusually asymmetrical and involved the lower extremities. On follow-up, BMSC often showed a decrease without complications. (orig.)

  10. Effect of inhaled formoterol and budesonide on exacerbations of asthma

    Pauwels, RA; Lofdahl, CG; Postma, DS; Tattersfield, AE; OByrne, P; Barnes, PJ; Ullman, A

    1997-01-01

    Background The role of long-acting, inhaled beta(2)-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. Methods After a four-week run-in period of treatment

  11. Terbutaline accumulates in blood and urine following daily therapeutic inhalation

    Krogh, Nanna; Rzeppa, Sebastian; Dyreborg, Anders

    2017-01-01

    ×d) of inhaled terbutaline. After inhalation of terbutaline at each trial, subjects performed 90 min of bike ergometer exercise at 65% of maximal oxygen consumption after which they stayed inactive. Blood and urine samples were collected before and after inhalation of terbutaline. Samples were analyzed by high...

  12. Evaluation of Inhaler Techniques Among Asthma Patients Seen in ...

    hanumantp

    Drug inhalation is an important and a common mode of .... to evaluate the use of inhaler technique among asthma patients in a .... The median duration of the use of the inhalers is 24 ..... Scalabrini A, Cukier A. Incorrect application technique of.

  13. Teaching inhaler use in chronic obstructive pulmonary disease patients.

    Lareau, Suzanne C; Hodder, Richard

    2012-02-01

    To review barriers to the successful use of inhalers in patients with chronic obstructive pulmonary disease (COPD), and the role of the nurse practitioner (NP) in facilitating optimum inhaler use. Review of the national and international scientific literature. Pharmacologic treatment of COPD patients comprises mainly inhaled medications. Incorrect use of inhalers is very common in these individuals. Some of the consequences of poor inhaler technique include reduced therapeutic dosing, medication adherence, and disease stability, which can lead to increased morbidity, decreased quality of life, and a high burden on the healthcare system. Knowledgeable evaluation and frequent reassessment of inhaler use coupled with education of patients, caregivers, and healthcare professionals can significantly improve the benefits COPD patients derive from inhaled therapy. Patient education is vital for correct use of inhalers and to ensure the effectiveness of inhaled medications. The NP has a critical role in assessing potential barriers to successful learning by the patient and improving inhaler technique and medication management. The NP can also facilitate success with inhaled medications by providing up-to-date inhaler education for other healthcare team members, who may then act as patient educators. ©2011 The Author(s) Journal compilation ©2011 American Academy of Nurse Practitioners.

  14. Knowledge of spacer device, peak flow meter and inhaler technique ...

    Background: Metered dose inhalers are cornerstone in effective management of bronchial asthma when correctly used. Most studies hitherto have focused on assessing patient's knowledge of inhaler technique. We sought to assess the knowledge of inhaler technique, spacer device and peak flow meter among doctors and ...

  15. 49 CFR 172.555 - POISON INHALATION HAZARD placard.

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false POISON INHALATION HAZARD placard. 172.555 Section... REQUIREMENTS, AND SECURITY PLANS Placarding § 172.555 POISON INHALATION HAZARD placard. (a) Except for size and color, the POISON INHALATION HAZARD placard must be as follows: ER22JY97.025 (b) In addition to...

  16. 49 CFR 172.429 - POISON INHALATION HAZARD label.

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false POISON INHALATION HAZARD label. 172.429 Section... REQUIREMENTS, AND SECURITY PLANS Labeling § 172.429 POISON INHALATION HAZARD label. (a) Except for size and color, the POISON INHALATION HAZARD label must be as follows: ER22JY97.023 (b) In addition to complying...

  17. Dosage of DTPA administration by inhalation

    Koizumi, Akira; Fukuda, Satoshi; Yamada, Yuji; Iida, Haruzo; Shimo, Michikuni

    2000-01-01

    The administration of DTPA by inhalation was examined as an emergency medical treatment. In order to estimate the practical dosage to the human, an accurate model of the human air way was connected to a anesthetizer and respiration was simulated. Ca-DTPA, aerosolized by an ultra-sonic nebulizer, was administered by inhalation to the model. For the experiments, the respiratory volume (tidal volume) and the respiration rate was 12 per minute. Irrigation water from the model of larynx and mouth, and the air filter were collected and measured by chelate titration in order to determine the quantity of aerosolized DTPA and the amount deposited on the trachea and lang. The results indicated that the quantity of aerosolized DTPA varied with dilution of the DTPA solution in a ample. It was found that a 3 time dilution was the most practical and that 73 mg of DTPA per minute could be aerosolized. Furthermore, the results indicated that 46% of the aerosolized DTPA was taken in through inhalation and that 26% of DTPA was deposited in the trachea and lung. These results suggest that in practical application in the emergency medical treatment, 15 minutes of inhalation could delivered to approximately 500 mg of DTPA, and 130 mg could be delivered to the trachea and lung. It is considered that these quantity are enough amount to increase the effects of radioactive nuclides from the body, comparing with the recommended dosage for injection administration. (author)

  18. Aerosol lung inhalation scintigraphy in normal subjects

    Sui, Osamu; Shimazu, Hideki

    1985-03-01

    We previously reported basic and clinical evaluation of aerosol lung inhalation scintigraphy with /sup 99m/Tc-millimicrosphere albumin (milli MISA) and concluded aerosol inhalation scintigraphy with /sup 99m/Tc-milli MISA was useful for routine examination. But central airway deposit of aerosol particles was found in not only the patients with chronic obstructive pulmonary disease (COPD) but also normal subjects. So we performed aerosol inhalation scintigraphy in normal subjects and evaluated their scintigrams. The subjects had normal values of FEVsub(1.0)% (more than 70%) in lung function tests, no abnormal findings in chest X-ray films and no symptoms and signs. The findings of aerosol inhalation scintigrams in them were classified into 3 patterns; type I: homogeneous distribution without central airway deposit, type II: homogeneous distribution with central airway deposit, type III: inhomogeneous distribution. These patterns were compared with lung function tests. There was no significant correlation between type I and type II in lung function tests. Type III was different from type I and type II in inhomogeneous distribution. This finding showed no correlation with %VC, FEVsub(1.0)%, MMF, V radical50 and V radical50/V radical25, but good correlation with V radical25 in a maximum forced expiratory flow-volume curve. Flow-volume curve is one of the sensitive methods in early detection of COPD, so inhomogeneous distribution of type III is considered to be due to small airway dysfunction.

  19. Elemental Concentration of Inhalable and Respirable Particulate ...

    20537 and respirable foam for I.O.M sampler. The elemental composition (Co, Ni, Zn, Cu, Fe, Pb, Cr, Mn and Cd) were analyzed by using Atomic Absorption Spectrophotometric (AAS). The data generated were subjected to descriptive analysis. In inhalable fraction,the enrichment factor ranged from 1-73.3 while in respirable ...

  20. Know How to Use Your Asthma Inhaler

    Full Text Available ... Facebook Tweet Share Compartir You can control your asthma and avoid an attack by taking your medicine exactly as your doctor ... and by avoiding things that can cause an attack. Watch a video to follow ... keep them with your Asthma Action Plan. Using a metered dose inhaler with ...

  1. Know How to Use Your Asthma Inhaler

    Full Text Available ... Controlling Tools for Control Triggers Indoors In the Workplace Outdoors Management Asthma Action Plan Flu Shots Inhalers ... clinics/physicians’ office Mixed Age Groups – Pharmacies Pregnant Women – Home Pregnant Women – Medical clinics/physicians’ office Health ...

  2. Dry powder inhalers for pulmonary drug delivery

    Frijlink, H.W.; De Boer, A.H.

    2004-01-01

    The pulmonary route is an interesting route for drug administration, both for effective local therapy (asthma, chronic obstructive pulmonary disease or cystic fibrosis) and for the systemic administration of drugs (e.g., peptides and proteins). Well-designed dry powder inhalers are highly efficient

  3. Report of the panel on inhaled actinides

    Anon.

    1978-01-01

    Some topics discussed are as follows: assessment of risks to man of inhaling actinides; use of estimates for developing protection standards; epidemiology of lung cancer in exposed human populations; development of respiratory tract models; and effects in animals: dose- and effect-modifying factors

  4. Treatment of proctalgia fugax with salbutamol inhalation.

    Eckardt, V F; Dodt, O; Kanzler, G; Bernhard, G

    1996-04-01

    Although no generally effective treatment for proctalgia fugax is known, inhalation of salbutamol has been reported to shorten pain attacks in isolated cases. We conducted a randomized, double-blind, placebo-controlled, crossover trial of inhaled salbutamol in 18 patients with proctalgia fugax. The clinical effect was evaluated by recording the duration of severe pain and discomfort during acute attacks. In addition, anorectal motility recordings were analyzed for possible changes in anal resting tone, sphincter relaxation during rectal distension and in rectal compliance prior to and following administration of the two test substances. Sixteen patients completed all investigations. Compared to placebo, salbutamol inhalation shortened the duration of severe pain (p = 0.019). The effect was most marked in patients having prolonged attacks. In the asymptomatic state, neither salbutamol nor placebo led to a significant change in anal resting pressure, anal relaxation during rectal distension, or rectal compliance. Salbutamol also did not alter the threshold for rectal sensation. Salbutamol inhalation shortens attacks of severe pain in patients with proctalgia fugax. The mechanism of this effect remains unexplained.

  5. A breath actuated dry powder inhaler

    de Boer, Anne; Frijlink, Henderik W.; Hagedoorn, Paul

    2015-01-01

    A breath actuated dry powder inhaler with a single air circulation chamber for de-agglomeration of entrained powdered medicament using the energy of the inspiratory air stream. The chamber has a substantially polygonal sidewall, a plurality of air supply channels entering the chamber substantially

  6. Inhalation drug delivery devices: technology update

    Ibrahim M

    2015-02-01

    Full Text Available Mariam Ibrahim, Rahul Verma, Lucila Garcia-ContrerasDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: The pulmonary route of administration has proven to be effective in local and systemic delivery of miscellaneous drugs and biopharmaceuticals to treat pulmonary and non-pulmonary diseases. A successful pulmonary administration requires a harmonic interaction between the drug formulation, the inhaler device, and the patient. However, the biggest single problem that accounts for the lack of desired effect or adverse outcomes is the incorrect use of the device due to lack of training in how to use the device or how to coordinate actuation and aerosol inhalation. This review summarizes the structural and mechanical features of aerosol delivery devices with respect to mechanisms of aerosol generation, their use with different formulations, and their advantages and limitations. A technological update of the current state-of-the-art designs proposed to overcome current challenges of existing devices is also provided.Keywords: pulmonary delivery, asthma, nebulizers, metered dose inhaler, dry powder inhaler

  7. Inhalation of antibiotics in cystic fibrosis

    Touw, D J; Brimicombe, R W; Hodson, M E; Heijerman, H G; Bakker, W

    Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of

  8. Pneumonitis after Inhalation of Mercury Vapours

    JD Glezos

    2006-01-01

    Full Text Available A 43-year-old man presented to hospital with pneumonia but only after discharge from hospital did he admit to deliberate prior inhalation of mercury. His pulmonary involvement appeared to resolve almost completely with antibiotics and supportive care. Nevertheless, persisting elevated urinary excretion of mercury required two courses of chelation therapy. No serious systemic sequelae were observed.

  9. Fate of inhaled azodicarbonamide in rats

    Mewhinney, J.A.; Ayres, P.H.; Bechtold, W.E.; Dutcher, J.S.; Cheng, Y.S.; Bond, J.A.; Medinsky, M.A.; Henderson, R.F.; Birnbaum, L.S.

    1987-01-01

    Azodicarbonamide (ADA) is widely used as a blowing agent in the manufacture of expanded foam plastics, as an aging and bleaching agent in flour, and as a bread dough conditioner. Human exposures have been reported during manufacture as well as during use. Groups of male F344/N rats were administered ADA by gavage, by intratracheal instillation, and by inhalation exposure to determine the disposition and modes of excretion of ADA and its metabolites. At 72 hr following gavage, 30% of the administered ADA was absorbed whereas following intratracheal instillation, absorption was 90%. Comparison between groups of rats exposed by inhalation to ADA to achieve body burdens of 24 or 1230 micrograms showed no significant differences in modes or rates of excretion of [ 14 C]ADA equivalents. ADA was readily converted to biurea under physiological conditions and biurea was the only 14 C-labeled compound present in excreta. [ 14 C]ADA equivalents were present in all examined tissues immediately after inhalation exposure, and clearance half-times on the order of 1 day were evident for all tissues investigated. Storage depots for [ 14 C]ADA equivalents were not observed. The rate of buildup of [ 14 C]ADA equivalents in blood was linearly related to the lung content as measured from rats withdrawn at selected times during a 6-hr inhalation exposure at an aerosol concentration of 25 micrograms ADA/liter. In a study extending 102 days after exposure, retention of [ 14 C]ADA equivalents in tissues was described by a two-component negative exponential function. The results from this study indicate that upon inhalation, ADA is rapidly converted to biurea and that biurea is then eliminated rapidly from all tissues with the majority of the elimination via the urine

  10. Workplace Inhalant Abuse in Adult Female: Brief Report

    Rohit Verma

    2011-01-01

    Full Text Available Inhalant abuse is the purposeful inhalation of intoxicating gases and vapors for the purpose of achieving an altered mental state. With its propensity for being yet an under-recognized form of substance use, being gateway to hard substances, cross-cultural penetration crossing socioeconomic boundaries, and causing significant morbidity and mortality in early ages, the prevention of inhalant misuse is a highly pertinent issue. This clinical report identifies a newer perspective in the emergence of inhalant abuse initiation. We report a case of an adult female with late onset of inhalant dependence developing at workplace and recommend for greater awareness, prevention, and management of this expanding substance abuse problem.

  11. Studies on the toxic effects of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on early embryonic development of SD rat

    Zheng-mou DONG

    2011-01-01

    Full Text Available Objective To evaluate the toxic effects of periodontal sustained release drug containing ornidazole and pefloxacin mesylate on early embryonic development of SD rats.Methods A total of 100female SD rats were randomly divided into negative control,low-,medium-,high-dose group and intervention group(20each.Rats in low-,medium-and high-dose group were fed daily with the sustained release drug at 1,4,and 8g/kg respectively;those in negative control group were fed daily with distilled water from the 14th day before mating to the 7th day of pregnancy continuously,and those in intervention group received cyclophosphamide(40mg/kgby intraperitoneal injection for 5successive days.During this period,the general status,mating,pregnancy,coefficient of ovary and uterus,the numbers of corpus luteum,nidation,live births,stillbirths,absorbed embryo,prenidatory and postnidatory mortality,serum testosterone(Tand estradiol(E2were determined respectively.Histopathologic examination of the ovary and uterus,immunohistochemical observation of ovaries for proliferating cell nuclear antigen(PCNAand Bcl-2associated X protein(Baxwere also performed respectively.Results The general status of those rats was good except one in the low-dose group and one in the intervention group died on the 14th day of administration,and one in negative control and one in high dose group died on the 5th day of pregnancy,respectively.The body weight of animals decreased significantly(P 0.05.The serum T level in medium-and high-dose group and the E2level in high-dose group declined compared to that in negative control group(P < 0.05.Conclusions Although the periodontal sustained release drug containing ornidazole and pefloxacin mesylate shows no toxicity to the early embryonic development of SD rats,the high dose drug has certain toxicity to ovary.Declined serum concentrations of T and E2,reduced expression of PCNA,and increased Bax may be the causes of the toxicity.

  12. Multi criteria decision making to select the best method for the preparation of solid lipid nanoparticles of rasagiline mesylate using analytic hierarchy process

    Viveksarathi Kunasekaran

    2014-01-01

    Full Text Available The objective of this study was to select best method for the development of rasagiline mesylate (RM loaded nanoscale solid lipid particles using analytic hierarchy process (AHP. Improper method selection may lead to waste of time, loss of material and financial resources. One of the possibilities to overcome these difficulties, AHP was employed to find the suitable method. In the AHP, a decision of hierarchy was constructed with a goal, criteria, sub-criteria, and alternatives. After constructing the AHP, the expert choice software was used to compute the overall priority of criteria, sub-criteria and alternatives. The best alternative selected was based on the highest priority. Nanoscale solid lipid particles of RM was formulated by the selected microemulsion method (M4 and it shows the particle size, polydispersity index and zeta potential were within acceptable limits. Drug content and entrapment efficiency of the RM-solid lipid nanoparticles were 97.26% and 86.57%, respectively. This study concludes that the AHP was viable and effective tool for selecting a most suitable method for the fabrication of RM loaded nanoscale solid lipid particles.

  13. Penetrable silica microspheres for immobilization of bovine serum albumin and their application to the study of the interaction between imatinib mesylate and protein by frontal affinity chromatography.

    Ma, Liyun; Li, Jing; Zhao, Juan; Liao, Han; Xu, Li; Shi, Zhi-guo

    2016-01-01

    In the current study, novel featured silica, named penetrable silica, simultaneously containing macropores and mesopores, was immobilized with bovine serum albumin (BSA) via Schiff base method. The obtained BSA-SiO2 was employed as the high-performance liquid chromatographic (HPLC) stationary phase. Firstly, D- and L-tryptophan were used as probes to investigate the chiral separation ability of the BSA-SiO2 stationary phase. An excellent enantioseparation factor was obtained up to 4.3 with acceptable stability within at least 1 month. Next, the BSA-SiO2 stationary phase was applied to study the interaction between imatinib mesylate (IM) and BSA by frontal affinity chromatography. A single type of binding site was found for IM with the immobilized BSA, and the hydrogen-bonding and van der Waals interactions were expected to be contributing interactions based on the thermodynamic studies, and this was a spontaneous process. Compared to the traditional silica for HPLC stationary phase, the proposed penetrable silica microsphere possessed a larger capacity to bond more BSA, minimizing column overloading effects and enhancing enantioseparation ability. In addition, the lower running column back pressure and fast mass transfer were meaningful for the column stability and lifetime. It was a good substrate to immobilize biomolecules for fast chiral resolution and screening drug-protein interactions.

  14. O tratamento da Leucemia Mielóide Crônica com mesilato de imatinibe Therapy of Chronic Myeloid Leukemia with imatinib mesylate

    Vaneuza M. Funke

    2008-04-01

    Full Text Available O mesilato de imatinibe é atualmente o tratamento de escolha para pacientes com Leucemia mielóide Crônica (LMC recém-diagnosticados. Desde os primeiros estudos clínicos em 1998 até o estudo IRIS, que comparou o uso em primeira linha de imatinibe com interferon + ara-C, esta droga vem se consolidando em segurança e eficácia. Ainda há, entretanto questionamentos sobre a melhor dose inicial, a identificação dos pacientes que mais se beneficiariam e a melhor abordagem frente a respostas sub-ótimas e resistência. Os principais estudos clínicos publicados com mesilato de imatinibe são revisados no presente artigo, e discutidos sob a perspectiva da realidade brasileira.Imatinib mesylate is currently the gold-standard therapy for patients with newly diagnosed Chronic Myelogenous Leukemia. From the clinical trials in 1998 to the IRIS study, which compared first line imatinib treatment with interferon and low dose ara-C, this drug has been consolidated in regards to its safety and efficacy. There are still some questions to answer. Which would be the best initial dose? Are there any patients who benefit more than others? What is the best approach to suboptimal response and resistance? The most important published clinical studies are reviewed in the current article and discussed from a Brazilian perspective.

  15. Quality-by-design based development of a self-microemulsifying drug delivery system to reduce the effect of food on Nelfinavir mesylate.

    Kamboj, Sunil; Rana, Vikas

    2016-03-30

    Poor aqueous solubility and moderate permeability of Nelfinavir mesylate (NFM) leads to high variability in absorption after oral administration. To improve the solubility and bioavailability of NFM, the self microemulsifying drug delivery system (SMEDDS) was developed. For this purpose, Quality by design (QbD) approach employing D-optimal mixture design was used to prepare SMEDDS of NFM. Further, the software generated numerically optimized SMEDDS were developed by utilizing desirability function. Maisine 35-1, Tween 80, and Transcutol HP were identified as oil, surfactant, and co-surfactant that had best solubility for NFM. Ternary phase diagrams were plotted to identify the self-emulsification region. Dissolution of putative NFM in simulated fasted or fed small intestinal conditions, respectively, predicted that there is a positive food effect. However, NFM loaded SMEDDS showed absence of food effect with no significant difference in dissolution performance either in Fasted or fed state simulated intestinal fluid (FaSSIF or FeSSIF) biorelevent dissolution media. The prepared SMEDDS were thermodynamically stable with droplet size (121 nm), poly dispersity index (PDI) (0.198) and emulsification time (food effect on pure NFM suspension. However, absence of food effect and 3.5-3.6 fold enhancement in the oral bioavailability was observed when NFM was formulated into SMEDDS. Thus, it could be envisaged that development of SMEDDS formulation of NFM could be one of the best alternative to enhance oral bioavailability of NFM. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Administration of imatinib mesylate in rats impairs the neonatal development of intramuscular interstitial cells in bladder and results in altered contractile properties.

    Gevaert, Thomas; Hutchings, Graham; Everaerts, Wouter; Prenen, Hans; Roskams, Tania; Nilius, Bernd; De Ridder, Dirk

    2014-04-01

    The KIT receptor is considered as a reliable marker for a subpopulation of interstitial cells (IC), and by persistent neonatal inhibition of KIT we have investigated the role of this receptor in the development of IC-networks in bladder and we have observed the functional consequences of this inhibition. Newborn rat pups were treated daily with the KIT inhibitor imatinib mesylate (IM). After 7 days animals were sacrificed and bladder samples were dissected for morphological and functional studies. Morphological research consisted of immunohistochemistry with IC specific antigens (KIT and vimentin) and electron microscopy. The functional studies were based on isolated bladder strips in organ baths, in which spontaneous bladder contractility and the response to a non-subtype selective muscarinic agonist was evaluated. Suburothelial and intramuscular IC were found and characterized in neonatal rat bladder. IM-treatment induced a significant decrease in numbers of IC based on specific immunohistochemical markers, and electron microscopy revealed evidence of IC cell injury. These morphological alterations were observed on intramuscular IC only and not on IC in the suburothelium. Isolated muscle strips from IM-treated animals had a lower contractile frequency and an altered response to muscarinic agonists. The present study shows the presence of regional subpopulations of IC in neonatal rat bladder, provides evidence for a dependence on KIT of the development of intramuscular IC and supports the hypothesis that a poor development of networks of intramuscular IC might have repercussions on spontaneous and muscarinic-induced bladder contractility. © 2013 Wiley Periodicals, Inc.

  17. The Effects of Imatinib Mesylate on Cellular Viability, Platelet Derived Growth Factor and Stem Cell Factor in Mouse Testicular Normal Leydig Cells.

    Kheradmand, Fatemeh; Hashemnia, Seyyed Mohammad Reza; Valizadeh, Nasim; Roshan-Milani, Shiva

    2016-01-01

    Growth factors play an essential role in the development of tumor and normal cells like testicular leydig cells. Treatment of cancer with anti-cancer agents like imatinib mesylate may interfere with normal leydig cell activity, growth and fertility through failure in growth factors' production or their signaling pathways. The purpose of the study was to determine cellular viability and the levels of, platelet derived growth factor (PDGF) and stem cell factor (SCF) in normal mouse leydig cells exposed to imatinib, and addressing the effect of imatinib on fertility potential. The mouse TM3 leydig cells were treated with 0 (control), 2.5, 5, 10 and 20 μM imatinib for 2, 4 and 6 days. Each experiment was repeated three times (15 experiments in each day).The cellular viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, one-way ANOVA with Tukey's post hoc and Kruskal-Wallis test were performed. A p-value less than 0.05 was considered statistically significant. With increasing drug concentration, cellular viability decreased significantly (pcellular viability, PDGF and SCF levels. Imatinib may reduce fertility potential especially at higher concentrations in patients treated with this drug by decreasing cellular viability. The effect of imatinib on leydig cells is associated with PDGF stimulation. Of course future studies can be helpful in exploring the long term effects of this drug.

  18. Insulin inhalation for diabetic patients: Nursing considerations

    Hanan Mohammed Mohammed

    2016-04-01

    Full Text Available Scientific knowledge has advanced to enable the development of inhaled insulin. It is a form of diabetes medication administered via the pulmonary system that studies have shown to be efficacious in the treatment of both type 1 and type 2 diabetes. Inhaled insulin is a new, safe means to deliver insulin that may increase patient compliance with insulin therapy, helping them to achieve optimal glycemic control and possibly reducing their risk of developing cardiovascular complications. However, diabetes is a chronic illness requiring lifetime intervention. Empowering patients with the knowledge of the diabetes disease process may give them the confidence to be more autonomous in managing their diabetes. HIIP gives nurse practitioners a new option that may improve their patients’ acceptance of insulin therapy, and improve glycemic control.

  19. Evaluating inhaler use technique in COPD patients

    Pothirat C

    2015-07-01

    Full Text Available Chaicharn Pothirat, Warawut Chaiwong, Nittaya Phetsuk, Sangnual Pisalthanapuna, Nonglak Chetsadaphan, Woranoot Choomuang Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Background: Poor inhalation techniques are associated with decreased medication delivery and poor disease control in chronic obstructive pulmonary disease (COPD. The purpose of this study was to evaluate techniques for using inhaler devices in COPD patients.Methods: A prospective cross-sectional study was conducted to assess patient compliance with correct techniques for using inhaler devices across four regimens, ie, the pressurized metered-dose inhaler (pMDI, the pMDI with a spacer, the Accuhaler®, and the Handihaler®. The percentage of compliance with essential steps of correct device usage for each regimen was recorded without prior notification when COPD patients presented for a routine visit, and 1 month after receiving face-to-face training. We compared the percentage of compliance between the devices and risk factors related to incorrect techniques using logistic regression analysis. Percentage of patient compliance with correct techniques was compared between the two visits using the chi-square test. Statistical significance was set at P<0.05.Results: A total of 103 COPD patients (mean age 71.2±9.2 years, males 64.1%, low education level 82.5%, and percent predicted forced expiratory volume in 1 second 51.9±22.5 were evaluated. Seventy-seven patients (74.8% performed at least one step incorrectly. Patients using the Handihaler had the lowest compliance failure (42.5%, and the odds ratio for failure with the other devices compared with the Handihaler were 4.6 (95% confidence interval [CI] 1.8–11.8 for the pMDI, 3.1 (95% CI 1.2–8.2 for the pMDI with a spacer, and 2.4 (95% CI 1.1–5.2 for the Accuhaler. Low education level was the single most important factor related

  20. Inhaled medicinal cannabis and the immunocompromised patient.

    Ruchlemer, Rosa; Amit-Kohn, Michal; Raveh, David; Hanuš, Lumír

    2015-03-01

    Medicinal cannabis is an invaluable adjunct therapy for pain relief, nausea, anorexia, and mood modification in cancer patients and is available as cookies or cakes, as sublingual drops, as a vaporized mist, or for smoking. However, as with every herb, various microorganisms are carried on its leaves and flowers which when inhaled could expose the user, in particular immunocompromised patients, to the risk of opportunistic lung infections, primarily from inhaled molds. The objective of this study was to identify the safest way of using medicinal cannabis in immunosuppressed patients by finding the optimal method of sterilization with minimal loss of activity of cannabis. We describe the results of culturing the cannabis herb, three methods of sterilization, and the measured loss of a main cannabinoid compound activity. Systematic sterilization of medicinal cannabis can eliminate the risk of fatal opportunistic infections associated with cannabis among patients at risk.

  1. Inhaled Antibiotics for Ventilator-Associated Infections.

    Palmer, Lucy B

    2017-09-01

    Multidrug-resistant organisms are creating a challenge for physicians treating the critically ill. As new antibiotics lag behind the emergence of worsening resistance, intensivists in countries with high rates of extensively drug-resistant bacteria are turning to inhaled antibiotics as adjunctive therapy. These drugs can provide high concentrations of drug in the lung that could not be achieved with intravenous antibiotics without significant systemic toxicity. This article summarizes current evidence describing the use of inhaled antibiotics for the treatment of bacterial ventilator-associated pneumonia and ventilator-associated tracheobronchitis. Preliminary data suggest aerosolized antimicrobials may effectively treat resistant pathogens with high minimum inhibitory concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Inhalation of nanoplatelets - Theoretical deposition simulations.

    Sturm, Robert

    2017-12-01

    Primary objective of the contribution was the theoretical prediction of nanoplatelet deposition in the human respiratory tract. Modeling was founded on the hypothetical inhalation of graphene nanoplatelets (GNP) measuring 0.01 and 0.1μm in thickness and adopting a projected area diameter of 1-30μm. Particle uptake was assumed to take place with inhalation flow rates of 250, 500, 750, and 1000cm 3 s -1 , respectively. For an appropriate description of pulmonary particle behavior, transport of GNP in a stochastic lung structure and deposition formulae based on analytical and numerical studies were presupposed. The results obtained from the theoretical approach clearly demonstrate that GNP with a thickness of 0.01μm deposit in the respiratory tract by 20-50%, whereas GNP with a thickness of 0.1μm exhibit a deposition of 20-90%. Larger platelets deposit with higher probability than small ones. Increase of inhalation flow rate is accompanied by decreased deposition in the case of thin GNP, whilst thicker GNP are preferably accumulated in the extrathoracic region. Generation-specific deposition ranges from 0.05 to 7% (0.01μm) and from 0.05 to 9%, with maximum values being obtained in airway generation 20. In proximal airway generations (0-10), deposition is increased with inhalation flow rate, whereas in intermediate to distal generations a reverse effect may be observed. Health consequences of GNP deposition in different lung compartments are subjected to an intense debate. Copyright © 2017. Published by Elsevier GmbH.

  3. Animal Model Selection for Inhalational HCN Exposure

    2016-08-01

    effects. Following acute inhalation exposure in humans and animals, cyanide is found in the lung, heart, blood , kidneys, and brain (Ballantyne, 1983...Pritchard, 2007). Other direct or secondary effects associated with CN are reacting with the ferric and carbonyl group of enzymes (e.g. catalase...mechanisms occurs before myocardial depression. Clinically, an initial period of bradycardia and hypertension may occur, followed by hypotension with reflex

  4. Electrostatics in pharmaceutical aerosols for inhalation.

    Wong, Jennifer; Chan, Hak-Kim; Kwok, Philip Chi Lip

    2013-08-01

    Electrostatics continues to play an important role in pharmaceutical aerosols for inhalation. Despite its ubiquitous nature, the charging process is complex and not well understood. Nonetheless, significant advances in the past few years continue to improve understanding and lead to better control of electrostatics. The purpose of this critical review is to present an overview of the literature, with an emphasis on how electrostatic charge can be useful in improving pulmonary drug delivery.

  5. Influence of inhaled Ca-DTPA on the long-term effects of inhaled Pu nitrate

    Ballou, J.E.; Dagle, G.E.; McDonald, K.E.; Buschbom, R.L.

    1975-01-01

    Inhaled Ca-DTPA administered to rats in 6 weekly, one-hour treatments of 3 mg/rat did not affect weight gain or life-span compared to Pu burdened animals (78 nCi ILB) or nontreated controls. In addition, the drug did not appear to promote the development of malignant lung tumors and bone tumors in Pu burdened rats although one rat exposed only to Ca-DTPA aerosols did develop a malignant lung tumor. This single lung tumor can not be considered significant although the normal incidence of this lesion is quite low. Inhaled Ca-DTPA therapy administered 20 days after Pu inhalation showed little effect in reducing the lung burden of plutonium. Skeletal deposition was decreased possibly because Ca-DTPA was administered during a time of active translocation of the inhaled Pu when Pu may have been available for chelation in the blood. Inhaled Ca-DTPA therapy did not appear to be beneficial in reducing the number of malignant lung tumors or bone tumors in plutonium burdened rats but on the other hand the chelate did not appear to promote these lesions. (U.S.)

  6. Inhalation dose assessment for Maralinga and Emu

    Johnston, P.N.; Lokan, K.H.; Williams, G.A.

    1990-01-01

    Dose assessments for the inhalation of artificial radionuclides are presented for all types of contaminated areas at Maralinga and Emu. These enable Committed Effective Dose Equivalent (CEDE), to be estimated by scaling at any area of interest where activity concentrations are known. In the case of Aborigines, these dose are estimated assuming respirable dust loadings of 1 mg/m 3 for adults and 1.5 mg/m 3 for children and infants. Details of the calculations are presented in the appendix. The model of the respiratory system used in this assessment is that described in Interantional Commission on Radiological Protection (ICRP) Publication 30 (ICRP, 1979a). With the exception of Kuli, which is contaminated with uranium, at all other sites it is only the inhalation of plutonium and americium that contributes significantly to the dose, and of these 239 Pu is the largest contributor. Therefore, considering the long half lives of the radionuclides concerned, it appears that the inhalation problems highlighted by this dose assessment will not diminish significantly within any reasonable period of time and hence management strategies must be developed to deal with such problems. 32 refs., 5 tabs., 1 fig

  7. Inhaled Antibiotic Therapy in Chronic Respiratory Diseases

    Diego J. Maselli

    2017-05-01

    Full Text Available The management of patients with chronic respiratory diseases affected by difficult to treat infections has become a challenge in clinical practice. Conditions such as cystic fibrosis (CF and non-CF bronchiectasis require extensive treatment strategies to deal with multidrug resistant pathogens that include Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Burkholderia species and non-tuberculous Mycobacteria (NTM. These challenges prompted scientists to deliver antimicrobial agents through the pulmonary system by using inhaled, aerosolized or nebulized antibiotics. Subsequent research advances focused on the development of antibiotic agents able to achieve high tissue concentrations capable of reducing the bacterial load of difficult-to-treat organisms in hosts with chronic respiratory conditions. In this review, we focus on the evidence regarding the use of antibiotic therapies administered through the respiratory system via inhalation, nebulization or aerosolization, specifically in patients with chronic respiratory diseases that include CF, non-CF bronchiectasis and NTM. However, further research is required to address the potential benefits, mechanisms of action and applications of inhaled antibiotics for the management of difficult-to-treat infections in patients with chronic respiratory diseases.

  8. Fragrance sensitisers: Is inhalation an allergy risk?

    Basketter, David; Kimber, Ian

    2015-12-01

    It is well established that some fragrance substances have the potential to cause skin sensitisation associated with the development of allergic contact dermatitis (ACD). Fragrances are invariably relatively volatile leading to the consideration that inhalation of fragrances might be a relevant route for either the induction of allergic sensitisation or the elicitation of allergic reactions. Moreover, there has been increasing recognition that allergic sensitisation of the respiratory tract can be induced by topical exposure to certain chemical allergens. Here the central question addressed is whether inhalation exposure to fragrance allergens has the potential to cause skin and/or respiratory sensitisation via the respiratory tract, or elicit allergic symptoms in those already sensitised. In addressing those questions, the underlying immunobiology of skin and respiratory sensitisation to chemicals has been reviewed briefly, and the relevant experimental and clinical evidence considered. The essential mechanistic differences between skin and respiratory allergy appear consistent with other sources of information, including the phenomenon of ACD that can arise from topical exposure to airborne allergens, but in the absence of accompanying respiratory effects. The conclusion is that, in contrast to topical exposure (including topical exposure to airborne material), inhalation of fragrance sensitisers does not represent a health risk with respect to allergy. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Whole-body nanoparticle aerosol inhalation exposures.

    Yi, Jinghai; Chen, Bean T; Schwegler-Berry, Diane; Frazer, Dave; Castranova, Vince; McBride, Carroll; Knuckles, Travis L; Stapleton, Phoebe A; Minarchick, Valerie C; Nurkiewicz, Timothy R

    2013-05-07

    Inhalation is the most likely exposure route for individuals working with aerosolizable engineered nano-materials (ENM). To properly perform nanoparticle inhalation toxicology studies, the aerosols in a chamber housing the experimental animals must have: 1) a steady concentration maintained at a desired level for the entire exposure period; 2) a homogenous composition free of contaminants; and 3) a stable size distribution with a geometric mean diameter generation of aerosols containing nanoparticles is quite challenging because nanoparticles easily agglomerate. This is largely due to very strong inter-particle forces and the formation of large fractal structures in tens or hundreds of microns in size (6), which are difficult to be broken up. Several common aerosol generators, including nebulizers, fluidized beds, Venturi aspirators and the Wright dust feed, were tested; however, none were able to produce nanoparticle aerosols which satisfy all criteria (5). A whole-body nanoparticle aerosol inhalation exposure system was fabricated, validated and utilized for nano-TiO2 inhalation toxicology studies. Critical components: 1) novel nano-TiO2 aerosol generator; 2) 0.5 m(3) whole-body inhalation exposure chamber; and 3) monitor and control system. Nano-TiO2 aerosols generated from bulk dry nano-TiO2 powders (primary diameter of 21 nm, bulk density of 3.8 g/cm(3)) were delivered into the exposure chamber at a flow rate of 90 LPM (10.8 air changes/hr). Particle size distribution and mass concentration profiles were measured continuously with a scanning mobility particle sizer (SMPS), and an electric low pressure impactor (ELPI). The aerosol mass concentration (C) was verified gravimetrically (mg/m(3)). The mass (M) of the collected particles was determined as M = (Mpost-Mpre), where Mpre and Mpost are masses of the filter before and after sampling (mg). The mass concentration was calculated as C = M/(Q*t), where Q is sampling flowrate (m(3)/min), and t is the sampling

  10. Special aspects of pharmacokinetics of inhalation anesthesia.

    Hendrickx, J F A; De Wolf, A

    2008-01-01

    Recent interest in the use of low-flow or closed circuit anesthesia has rekindled interest in the pharmacokinetics of inhaled anesthetics. The kinetic properties of inhaled anesthetics are most often modeled by physiologic models because of the abundant information that is available on tissue solubilities and organ perfusion. These models are intuitively attractive because they can be easily understood in terms of the underlying anatomy and physiology. The use of classical compartment modeling, on the other hand, allows modeling of data that are routinely available to the anesthesiologist, and eliminates the need to account for every possible confounding factor at each step of the partial pressure cascade of potent inhaled agents. Concepts used to describe IV kinetics can readily be applied to inhaled agents (e.g., context-sensitive half-time and effect site concentrations). The interpretation of the F(A)/F(I) vs time curve is expanded by reintroducing the concept of the general anesthetic equation-the focus is shifted from "how F(A) approaches F(I)" to "what combination of delivered concentration and fresh gas flow (FGF) can be used to attain the desired F(A)." When the desired F(A) is maintained with a FGF that is lower than minute ventilation, rebreathing causes a discrepancy between the concentration delivered by the anesthesia machine (=selected by the anesthesiologist on the vaporizer, F(D)) and that inspired by the patient. This F(D)-F(I) discrepancy may be perceived as "lack of control" and has been the rationale to use a high FGF to ensure the delivered matched the inspired concentration. Also, with low FGF there is larger variability in F(D) because of interpatient variability in uptake. The F(D)-F(I) discrepancy increases with lower FGF because of more rebreathing, and as a consequence the uptake pattern seems to be more reflected in the F(D) required to keep F(A) constant. The clinical implication for the anesthesiologist is that with high FGF few F

  11. E-cigarette versus nicotine inhaler: comparing the perceptions and experiences of inhaled nicotine devices.

    Steinberg, Michael B; Zimmermann, Mia Hanos; Delnevo, Cristine D; Lewis, M Jane; Shukla, Parth; Coups, Elliot J; Foulds, Jonathan

    2014-11-01

    Novel nicotine delivery products, such as electronic cigarettes (e-cigarettes), have dramatically grown in popularity despite limited data on safety and benefit. In contrast, the similar U.S. Food and Drug Administration (FDA)-approved nicotine inhaler is rarely utilized by smokers. Understanding this paradox could be helpful to determine the potential for e-cigarettes as an alternative to tobacco smoking. To compare the e-cigarette with the nicotine inhaler in terms of perceived benefits, harms, appeal, and role in assisting with smoking cessation. A cross-over trial was conducted from 2012 to 2013 PARTICIPANTS/INTERVENTIONS: Forty-one current smokers age 18 and older used the e-cigarette and nicotine inhaler each for 3 days, in random order, with a washout period in between. Thirty-eight participants provided data on product use, perceptions, and experiences. The Modified Cigarette Evaluation Questionnaire (mCEQ) measured satisfaction, reward, and aversion. Subjects were also asked about each product's helpfulness, similarity to cigarettes, acceptability, image, and effectiveness in quitting smoking. Cigarette use was also recorded during the product-use periods. The e-cigarette had a higher total satisfaction score (13.9 vs. 6.8 [p e-cigarette received higher ratings for helpfulness, acceptability, and "coolness." More subjects would use the e-cigarette to make a quit attempt (76 %) than the inhaler (24 %) (p e-cigarette vs. 10 % (4/38) using the inhaler (p = 0.18). The e-cigarette was more acceptable, provided more satisfaction, and had higher perceived benefit than the inhaler during this trial. E-cigarettes have the potential to be important nicotine delivery products owing to their high acceptance and perceived benefit, but more data are needed to evaluate their actual efficacy and safety. Providers should be aware of these issues, as patients will increasingly inquire about them.

  12. Inhalant abuse in the youth : A reason for concern

    J Simlai

    2008-01-01

    Full Text Available In recent times Inhalant or Volatile substances are emerging as a major drug of abuse in the preadolescent and adolescent age group. Most of the children are from broken homes and poor backgrounds. Inhalants have serious immediate and longterm side-effects and can also cause sudden sniffing death syndrome. It is difficult to control this ever-growing problem because Inhalants or Solvents are widely available. Management issues have been discussed in the review.

  13. Economic considerations in the use of inhaled anesthetic agents.

    Golembiewski, Julie

    2010-04-15

    To describe the components of and factors contributing to the costs of inhaled anesthesia, basis for quantifying and comparing these costs, and practical strategies for performing pharmacoeconomic analyses and reducing the costs of inhaled anesthetic agents. Inhaled anesthesia can be costly, and some of the variable costs, including fresh gas flow rates and vaporizer settings, are potential targets for cost savings. The use of a low fresh gas flow rate maximizes rebreathing of exhaled anesthetic gas and is less costly than a high flow rate, but it provides less control of the level of anesthesia. The minimum alveolar concentration (MAC) hour is a measure that can be used to compare the cost of inhaled anesthetic agents at various fresh gas flow rates. Anesthesia records provide a sense of patterns of inhaled anesthetic agent use, but the amount of detail can be limited. Cost savings have resulted from efforts to reduce the direct costs of inhaled anesthetic agents, but reductions in indirect costs through shortened times to patient recovery and discharge following the judicious use of these agents are more difficult to demonstrate. The patient case mix, fresh gas flow rates typically used during inhaled anesthesia, availability and location of vaporizers, and anesthesia care provider preferences and practices should be taken into consideration in pharmacoeconomic evaluations and recommendations for controlling the costs of inhaled anesthesia. Understanding factors that contribute to the costs of inhaled anesthesia and considering those factors in pharmacoeconomic analyses and recommendations for use of these agents can result in cost savings.

  14. The Advantages of Low-Flow Inhalational Anesthesia

    P. Torok

    2005-01-01

    Full Text Available The paper deals with the economical and ecological use of inhalation anesthetics in low-flow anesthesia (LFA, 1—0.5 l/ min and high-flow anesthesia (HFA, more than 2—6 l/min. Four hundred and ninety six inhalational anesthesias lasting at least 80 minutes were analyzed in each group under consideration. The concentration of inhalation anesthetics was measures in the atmosphere of an operative theatre if inhalational anesthesia lasted more than 4 hours. There is evidence for the economical and ecological benefits in the use of LFA in terms of the availability of appropriate anesthesiological equipment, monitoring, and a highly skilled anesthesiologist.

  15. Oral versus inhaled antibiotics for bronchiectasis.

    Spencer, Sally; Felix, Lambert M; Milan, Stephen J; Normansell, Rebecca; Goeminne, Pieter C; Chalmers, James D; Donovan, Tim

    2018-03-27

    Bronchiectasis is a chronic inflammatory disease characterised by a recurrent cycle of respiratory bacterial infections associated with cough, sputum production and impaired quality of life. Antibiotics are the main therapeutic option for managing bronchiectasis exacerbations. Evidence suggests that inhaled antibiotics may be associated with more effective eradication of infective organisms and a lower risk of developing antibiotic resistance when compared with orally administered antibiotics. However, it is currently unclear whether antibiotics are more effective when administered orally or by inhalation. To determine the comparative efficacy and safety of oral versus inhaled antibiotics in the treatment of adults and children with bronchiectasis. We identified studies through searches of the Cochrane Airways Group's Specialised Register (CAGR), which is maintained by the Information Specialist for the group. The Register contains trial reports identified through systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched ClinicalTrials.gov and the WHO trials portal. We searched all databases in March 2018 and imposed no restrictions on language of publication. We planned to include studies which compared oral antibiotics with inhaled antibiotics. We would have considered short-term use (less than four weeks) for treating acute exacerbations separately from longer-term use as a prophylactic (4 weeks or more). We would have considered both intraclass and interclass comparisons. We planned to exclude studies if the participants received continuous or high-dose antibiotics immediately before the start of the trial, or if they have received a diagnosis of cystic fibrosis (CF), sarcoidosis, active allergic bronchopulmonary aspergillosis or active non-tuberculous Mycobacterial infection

  16. Health effects of inhaled gasoline engine emissions.

    McDonald, Jacob D; Reed, Matthew D; Campen, Matthew J; Barrett, Edward G; Seagrave, JeanClare; Mauderly, Joe L

    2007-01-01

    Despite their prevalence in the environment, and the myriad studies that have shown associations between morbidity or mortality with proximity to roadways (proxy for motor vehicle exposures), relatively little is known about the toxicity of gasoline engine emissions (GEE). We review the studies conducted on GEE to date, and summarize the findings from each of these studies. While there have been several studies, most of the studies were conducted prior to 1980 and thus were not conducted with contemporary engines, fuels, and driving cycles. In addition, many of the biological assays conducted during those studies did not include many of the assays that are conducted on contemporary inhalation exposures to air pollutants, including cardiovascular responses and others. None of the exposures from these earlier studies were characterized at the level of detail that would be considered adequate today. A recent GEE study was conducted as part of the National Environmental Respiratory Center (www.nercenter.org). In this study several in-use mid-mileage General Motors (Chevrolet S-10) vehicles were purchased and utilized for inhalation exposures. An exposure protocol was developed where engines were operated with a repeating California Unified Driving Cycle with one cold start per day. Two separate engines were used to provide two cold starts over a 6-h inhalation period. The exposure atmospheres were characterized in detail, including detailed chemical and physical analysis of the gas, vapor, and particle phase. Multiple rodent biological models were studied, including general toxicity and inflammation (e.g., serum chemistry, lung lavage cell counts/differentials, cytokine/chemokine analysis, histopathology), asthma (adult and in utero exposures with pulmonary function and biochemical analysis), cardiovascular effects (biochemical and electrocardiograph changes in susceptible rodent models), and susceptibility to infection (Pseudomonas bacteria challenge). GEE resulted in

  17. Lung dosimetry for inhaled radon progeny

    Hofmann, W.

    1986-01-01

    Lung cancer risk assessment for inhaled radon progeny requires a detailed knowledge of the dose distribution pattern throughout the human respiratory tract. Current lung dosimetry models take into acocunt aerosol deposition in a formalized airway structrue, modification of the initial deposition pattern by clearance mechanisms, and the energy deposited by alpha particles in sensitive cells of the bronchial epithelium. The resulting dose distribution pattern depends on the characteristics of the inhaled aerosol and the breathing pattern. Special emphasis has been laid on the age dependency of the anatomical structure of the human lung and the resulting doses, as well as on the rediological significance of enhanced aerosol deposition at bronchial bifuraction. The biological variability inherent in all morphometric, physiological and histological parameters involved in lung dosimetry suggests the application of stochastic modelling techniques. Examples for the use of Monte Carlo methods presented here are the random walk of inhaled particles through a random airway geometry, and the influence of the intra-subject variability of radiation doses on radiation protection standards. At the cellular level the concept of absorbed dose loses its significance and has to be replaced by microdosimetric concepts, such as internal microdosimtry or track structure theory. An image-analysis model allows us to construct specific energy distributions in sensitive lung cells. Application of a track structure model of alpha particle interaction with bronchial epithelial cells permits the calculation of probabilities for inactivation, transformation, and tumor induction. The latter has been used to analyse lung cancer risk at low doses in Chinese high background areas

  18. Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma

    Bisgaard, H; Klug, B; Sumby, B S

    1998-01-01

    (1) from the 8 yr old children, respectively. Similar particle fractions from the Budesonide Turbuhaler were 35 (9), 21 (10) and 7 (5) from 4 yr old children and 30 (7), 32 (9) and 12 (6) from 8 yr old children. In conclusion, the Diskus inhaler provides an improved dose consistency through...

  19. Inhalation treatment of primary lung cancer using liposomal curcumin dry powder inhalers

    Tongtong Zhang

    2018-05-01

    Full Text Available Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency. Key words: Curcumin, Dry powder inhaler, Liposome, Primary lung cancer, Pulmonary delivery

  20. Inhaled medication and inhalation devices for lung disease in patients with cystic fibrosis : A European consensus

    Heijerman, Harry; Westerman, Elsbeth; Conway, Steven; Touw, Daan; Döring, Gerd; Frijlink, Henderik

    In cystic fibrosis inhalation of drugs for the treatment of CF related lung disease has been proven to be highly effective. Consequently, an increasing number of drugs and devices have been developed for CF lung disease or are currently under development. In this European consensus document we

  1. Effects of WIN 55,212-2 mesylate on the anticonvulsant action of lamotrigine, oxcarbazepine, pregabalin and topiramate against maximal electroshock-induced seizures in mice.

    Luszczki, Jarogniew J; Wlaz, Aleksandra; Karwan, Slawomir; Florek-Luszczki, Magdalena; Czuczwar, Stanislaw J

    2013-11-15

    The aim of this study was to determine the effect of WIN 55,212-2 mesylate (WIN - a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of four second-generation antiepileptic drugs (lamotrigine, oxcarbazepine, pregabalin and topiramate) in the mouse maximal electroshock seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2s stimulus duration) delivered via auricular electrodes. Drug-related adverse effects were ascertained by use of the chimney test (evaluating motor performance), the step-through passive avoidance task (assessing long-term memory) and the grip-strength test (evaluating skeletal muscular strength). Total brain concentrations of antiepileptic drugs were measured by high-pressure liquid chromatography to ascertain any pharmacokinetic contribution to the observed antiseizure effect. Results indicate that WIN (5mg/kg, i.p.) significantly enhanced the anticonvulsant action of lamotrigine (Poxcarbazepine in the maximal electroshock-induced tonic seizure test in mice. Furthermore, none of the investigated combinations of WIN with antiepileptic drugs were associated with any concurrent adverse effects with regards to motor performance, long-term memory or muscular strength. Pharmacokinetic characterization revealed that WIN had no impact on total brain concentrations of lamotrigine, oxcarbazepine, pregabalin and topiramate in mice. These preclinical data would suggest that WIN in combination with lamotrigine, pregabalin and topiramate is associated with beneficial anticonvulsant pharmacodynamic interactions in the maximal electroshock-induced tonic seizure test. © 2013 Published by Elsevier B.V.

  2. Evaluation of a novel educational strategy, including inhaler-based reminder labels, to improve asthma inhaler technique.

    Basheti, Iman A; Armour, Carol L; Bosnic-Anticevich, Sinthia Z; Reddel, Helen K

    2008-07-01

    To evaluate the feasibility, acceptability and effectiveness of a brief intervention about inhaler technique, delivered by community pharmacists to asthma patients. Thirty-one pharmacists received brief workshop education (Active: n=16, CONTROL: n=15). Active Group pharmacists were trained to assess and teach dry powder inhaler technique, using patient-centered educational tools including novel Inhaler Technique Labels. Interventions were delivered to patients at four visits over 6 months. At baseline, patients (Active: 53, CONTROL: 44) demonstrated poor inhaler technique (mean+/-S.D. score out of 9, 5.7+/-1.6). At 6 months, improvement in inhaler technique score was significantly greater in Active cf. CONTROL patients (2.8+/-1.6 cf. 0.9+/-1.4, p<0.001), and asthma severity was significantly improved (p=0.015). Qualitative responses from patients and pharmacists indicated a high level of satisfaction with the intervention and educational tools, both for their effectiveness and for their impact on the patient-pharmacist relationship. A simple feasible intervention in community pharmacies, incorporating daily reminders via Inhaler Technique Labels on inhalers, can lead to improvement in inhaler technique and asthma outcomes. Brief training modules and simple educational tools, such as Inhaler Technique Labels, can provide a low-cost and sustainable way of changing patient behavior in asthma, using community pharmacists as educators.

  3. Systematic Review of Errors in Inhaler Use

    Sanchis, Joaquin; Gich, Ignasi; Pedersen, Søren

    2016-01-01

    in these outcomes over these 40 years and when partitioned into years 1 to 20 and years 21 to 40. Analyses were conducted in accordance with recommendations from Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Strengthening the Reporting of Observational Studies in Epidemiology. Results Data...... A systematic search for articles reporting direct observation of inhaler technique by trained personnel covered the period from 1975 to 2014. Outcomes were the nature and frequencies of the three most common errors; the percentage of patients demonstrating correct, acceptable, or poor technique; and variations...

  4. Asthma, inhaled corticosteroid treatment, and growth.

    Ninan, T K; Russell, G

    1992-01-01

    To evaluate the effects on growth of inhaled corticosteroid treatment (ICT) and of the quality of control of asthma, height velocity was studied in 58 prepubertal children attending a specialist asthma clinic because of chronic asthma that was difficult to control. The height velocity standard deviation (SD) score was maximal when the asthma was well controlled both before (0.01) and after (-0.07) starting ICT. It was least when the asthma was poorly controlled both before (-1.50) and after (...

  5. Skeletal lesions from inhaled plutonium in beagles

    Dagle, G.E.; Park, J.F.; Weller, R.E.; Ragan, H.A.; McClanahan, B.J.; Fisher, D.R.

    1984-10-01

    The report briefly reviews the skeletal effects observed in ongoing lifespan studies in beagle dogs at 13, 10, and 7 years, respectively, after inhalation exposure to 239 Pu oxide and nitrate or 238 Pu oxide. Plutonium nitrate was chosen to represent soluble material more readily translocated to bone and other tissues than the oxide. Bone lesions related to plutonium exposure were observed only in dogs exposed to 238 Pu oxide and 239 Pu nitrate. The skeleton accumulated approximately 2% ( 239 Pu oxide), 45% ( 238 Pu oxide) or 50% ( 239 Pu nitrate) of the final body burdens at 13, 10, and 7 years, respectively, after exposure. 11 references, 2 figures

  6. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

  7. The Toxicity of Inhaled Sulphur Mustard

    2012-10-01

    lobes, weighed and then dried in an oven (40 oC). The samples were weighed daily until a stable weight had been achieved (approx. 5 days), to...into account). Lung samples were taken, weighed and then dried in an oven (40o C) until a stable weight had been achieved, to determine lung wet...large porcine model: A 6 hour study. Inhal. Tox. (in press). 16. Garner JP, Watts S, Parry C, Bird J and Kirkman E. 2009. Development of a large

  8. Inhalation Exposure Method for Illegal Drugs.

    Inomata, Akiko; Ogata, Akio; Tada, Yukie; Nagasawa, Akemichi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Takahashi, Hiroshi; Kaihoko, Fujifumi; Tanaka, Kazuyoshi; Nakajima, Jun'ichi; Suzuki, Atsuko; Uemura, Nozomi; Moriyasu, Takako; Watanabe, Daisuke; Ishihara, Kei; Usami, Takashi; Kamei, Satoru; Kohno, Yasuaki

    2017-01-01

    We developed a new inhalation exposure method to evaluate effects of synthetic cannabimimetics that are being distributed as new, unregulated drugs in the Tokyo area. We selected the commercial product "SOUTOU" containing AB-CHMINACA and 5F-AMB as the test drug and dried marshmallow (Althaea officinalis) leaves as the negative control. A half cigarette packed with dried marshmallow leaves or SOUTOU was ignited, then mainstream smoke from each was delivered to five mice in an exposure box. After the cigarettes were fully consumed, neurobehavioral observations and a catalepsy test were performed at 15, 30 and 60 min after exposure. The effluent air from the exposure box was poured into impingers containing acetonitrile (first impinger) and dimethyl sulfoxide (second impinger). The resulting solutions were analyzed to assess decomposition of the synthetic cannabimimetics. Mice exposed to SOUTOU smoke showed many excitement behaviors and some suppressive behaviors at 15, 30 and 60 min. These clearly included cannabimimetic specific pharmacological actions. Negative control mice also showed some suppressive behaviors at 15 min but these were attenuated at later times, nearly disappearing at 60 min. In addition, the behavioral effects observed in controls were less pronounced than those in SOUTOU exposed mice. The inhalation exposure method developed in our study would be effective for determining cannabinoid specific pharmacological effects of illegal drugs, as well as for assessing the presence of active compound(s) by comparing the test substance with a negative control.

  9. Inhalational anaesthesia with low fresh gas flow

    Christian Hönemann

    2013-01-01

    Full Text Available During the inhalation of anaesthesia use of low fresh gas flow (0.35-1 L/min has some important advantages. There are three areas of benefit: pulmonary - anaesthesia with low fresh gas flow improves the dynamics of inhaled anaesthesia gas, increases mucociliary clearance, maintains body temperature and reduces water loss. Economic - reduction of anaesthesia gas consumption resulting in significant savings of > 75% and Ecological - reduction in nitrous oxide consumption, which is an important ozone-depleting and heat-trapping greenhouse gas that is emitted. Nevertheless, anaesthesia with high fresh gas flows of 2-6 L/min is still performed, a technique in which rebreathing is practically negligible. This special article describes the clinical use of conventional plenum vaporizers, connected to the fresh gas supply to easily perform low (1 L/min, minimal (0.5 L/min or metabolic flow anaesthesia (0.35 L/min with conventional Primus Draeger® anaesthesia machines in routine clinical practice.

  10. Alveolar proteinosis associated with aluminium dust inhalation.

    Chew, R; Nigam, S; Sivakumaran, P

    2016-08-01

    Secondary alveolar proteinosis is a rare lung disease which may be triggered by a variety of inhaled particles. The diagnosis is made by detection of anti-granulocyte-macrophage colony-stimulating factor antibodies in bronchoalveolar lavage fluid, which appears milky white and contains lamellar bodies. Aluminium has been suggested as a possible cause, but there is little evidence in the literature to support this assertion. We report the case of a 46-year-old former boilermaker and boat builder who developed secondary alveolar proteinosis following sustained heavy aluminium exposure. The presence of aluminium was confirmed both by histological examination and metallurgical analysis of a mediastinal lymph node. Despite cessation of exposure to aluminium and treatment with whole-lung lavage which normally results in improvements in both symptoms and lung function, the outcome was poor and novel therapies are now being used for this patient. It may be that the natural history in aluminium-related alveolar proteinosis is different, with the metal playing a mediating role in the disease process. Our case further supports the link between aluminium and secondary alveolar proteinosis and highlights the need for measures to prevent excessive aluminium inhalation in relevant industries. © The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Hematologic effects of inhaled plutonium in beagles

    Ragan, H.A.; Buschbom, R.L.; Park, J.F.; Dagle, G.E.; Weller, R.E.

    1986-01-01

    Beagle dogs were exposed, by inhalation, 5 to 11 years ago, to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 , at six dose levels resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Translocation of the plutonium to extrapulmonary sites was related to the physical-chemical characteristics of the plutonium compound. The highly insoluble 239 PuO 2 was retained primarily in the lung and associated lymph nodes, whereas 239 Pu(NO 3 ) 4 was much more soluble and translocated relatively rapidly to the skeleton and other extrapulmonary tissues. The 238 PuO 2 was intermediate in solubility and translocation characteristics. The hematologic effects of plutonium inhalation were most pronounced on lymphocyte populations. Evidence suggests that these effects result from irradiation of lymphocytes via the pulmonary lymph nodes with insoluble 239 PuO 2 , and via these same lymph nodes, extrapulmonary lymph nodes, and bone marrow lymphocytes with the more soluble forms, i.e., 238 PuO 2 and 239 Pu(NO 3 ) 4 . There is no evidence suggesting that these exposures increase the risk of developing myeloid or lymphoid neoplasia. 8 refs., 4 figs., 3 tabs

  12. The effect of smoking status on burn inhalation injury mortality.

    Knowlin, Laquanda; Stanford, Lindsay; Cairns, Bruce; Charles, Anthony

    2017-05-01

    Three factors that effect burn mortality are age, total body surface of burn (TBSA), and inhalation injury. Of the three, inhalation injury is the strongest predictor of mortality thus its inclusion in the revised Baux score (age+TBSA+17* (inhalation injury, 1=yes, 0=no)). However, the weighted contribution of specific comorbidities such as smoker status on mortality has traditionally not been accounted for nor studied in this subset of burn patients. We therefore sought to examine the impact of current tobacco and/or marijuana smoking in patients with inhalation injury. A retrospective analysis of patients admitted to a regional burn center from 2002 to 2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, and smoker status. Bivariate analysis was performed and logistic regression modeling using significant variables was utilized to estimate odds of mortality. There were a total of 7640 patients over the study period. 7% (n=580) of the burn cohort with inhalation injury were included in this study. In-hospital burn mortality for inhalation injury patients was 23%. Current smokers (20%) included cigarette smokers and marijuana users, 19% and 3%, respectively. Preexisting respiratory disease (17%) was present in 36% of smokers compared to 13% of non-smokers (psmoke inhalation injury. Future prospective studies in human and/or animal models are needed to confirm these findings. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  13. Inhalation of Budesonide/Formoterol Increases Diaphragm Muscle Contractility

    Chiyohiko Shindoh

    2012-01-01

    Conclusions: BUD/FORM inhalation has an inotropic effect on diaphragm muscle, protects diaphragm muscle deterioration after endotoxin injection, and inhibits NO production. Increments in muscle contractility with BUD/FORM inhalation are induced through a synergistic effect of an anti-inflammatory agent and 02-agonist.

  14. Influence of treatment with inhalable heroin on pulmonary function

    Buster, M. C. A.; van den Brink, W.; van Brussel, G. H. A.; van Ree, J. M.

    2011-01-01

    This study aims to asses the influence of inhalable heroin on pulmonary function in chronic heroin-dependent patients treated with inhalable heroin. Among 32 patients (all cigarette smokers), a spirometric test was conducted at baseline and after an average period of 10 months of treatment with

  15. Education on Correct Inhaler Technique in Pharmacy Schools ...

    Conclusion: Standard educational training may not be the most appropriate method of teaching students the correct use of inhalers. Clearly, there is a practice element missing which needs to be addressed in a feasible way. Keywords: Inhaler technique, Pharmacy education, Hands-on training, Training barrier ...

  16. Evaluation of Inhaler Techniques Among Asthma Patients Seen in ...

    Background: An Adequate and an effective dose of inhalation drugs can be administered only if the correct inhaler‑specific technique is followed by asthma patients. There is paucity of data on this subject among Nigerians and Africans. Aims: This observational study was to assess the inhaler techniques among asthma ...

  17. Personal exposure to inhalable cement dust among construction workers

    Peters, Susan; Kromhout, Hans; Thomassen, Yngvar; Fechter-Rink, Edeltraud

    2009-01-01

    A case study was carried out in 2006-2007 to assess the actual cement dust exposure among construction workers involved in a full-scale construction project and as a comparison among workers involved in various stages of cement and concrete production. Full-shift personal exposure measurements were performed for several job types. Inhalable dust and cement dust (based on analysis of elemental calcium) concentrations were determined. Inhalable dust exposures at the construction site ranged from 0.05 to 34 mg/m3, with a mean concentration of 1.0 mg/m3. For inhalable cement dust mean exposure was 0.3 mg/m3 (range 0.02-17 mg/m3). Reinforcement and pouring workers had the lowest average concentrations. Inhalable dust levels in the ready-mix and pre-cast concrete plants were, on average, below 0.5 mg/m3 for inhalable dust and below 0.2 mg/m3 for inhalable cement dust. Highest dust concentrations were measured in cement production, particularly during cleaning tasks (inhalable dust GM=55 mg/m3; inhalable cement dust GM=33 mg/m3) at which point the workers wore personal protective equipment. Elemental measurements showed highest but very variable cement percentages in the cement plant and very low percentages of cement during reinforcement work and pouring.

  18. Use of nitrite inhalants ("poppers") among American youth.

    Wu, Li-Tzy; Schlenger, William E; Ringwalt, Chris L

    2005-07-01

    We examined the patterns and correlates of nitrite inhalant use among adolescents aged 12 to 17 years. Study data were drawn from the 2000 and 2001 National Household Surveys on Drug Abuse. Logistic regression was used to identify the characteristics associated with nitrite inhalant use. Among adolescents aged 12 to 17 years, 1.5% reported any lifetime use of nitrite inhalants. The prevalence of lifetime nitrite inhalant use increased to 12% and 14% among adolescents who were dependent on alcohol and any drug in the past year, respectively. Many nitrite inhalant users used at least three other types of inhalants (68%) and also met the criteria for alcohol (33%) and drug (35%) abuse or dependence. Increased odds of nitrite inhalant use were associated with residing in nonmetropolitan areas, recent utilization of mental health services, delinquent behaviors, past year alcohol and drug abuse and dependence, and multi-drug use. Adolescents who had used nitrite inhalants at least once in their lifetime tend to engage in delinquent activities and report co-occurring multiple drug abuse and mental health problems in the past year.

  19. Conference report: 1st Medicon Valley Inhalation Symposium.

    Lastow, Orest

    2013-02-01

    The 1st Medicon Valley Inhalation Symposium was arranged by the Medicon Valley Inhalation Consortium. It was held at the Medicon Village site, which is the former AstraZeneca site in Lund, Sweden. It was a 1-day symposium focused on inhaled drug delivery and inhalation product development. A total of 90 delegates listened to 15 speakers. The program was organized to follow the value chain of an inhalation product development. The benefits and future opportunities of inhaled drug delivery were discussed together with some new disease areas that can be targeted with inhalation. The pros and cons of the two main formulation types; dry powder and liquid formulations, were discussed by a panel. The different requirements of the drug molecules from a pharmacology, chemical and physical perspective were explained. The modeling of the physics inside an inhaler was demonstrated and the potential strategic benefits of device design were highlighted together with the many challenges of formulation manufacturing. Lung deposition mechanisms and the difficulties of the generic bioequivalence concept were discussed. Using an anatomically correct impactor inlet is a valuable tool in lung deposition predictions and the planning of clinical trials. The management of the biological material generated in clinical studies is key to successful studies.

  20. Lung deposition of inhaled drugs increases with age

    Onhøj, J; Thorsson, L; Bisgaard, H

    2000-01-01

    Budesonide plasma concentrations after inhalation of a fixed dose of the drug from a pressurized metered dose inhaler (pMDI) with spacer (Nebuchamber) were compared in young children and adults: 26 patients with mild asthma comprising 8 children 2-3 yr, 8 children 4-6 yr, and 10 adults 20-41 yr...

  1. Inhaling habits among smokers of different types of cigarette

    Wald, N.J.; Idle, M.; Boreham, J.; Bailey, A.

    1980-12-01

    Inhaling habits were studied in 1316 men who freely smoked their usual brands of cigarette. An index of inhaling was calculated for each person by dividing the estimated increase in carboxyhaemoglobin level from a standard number of cigarettes by the carbon monoxide yield of the cigarette smoked. Smokers of ventilated filter cigarettes inhaled 82% more than smokers of plain cigarettes (p less than 0.001) and those who smoked unventilated filter cigarettes inhaled 36% more (p less than 0.001). Cigarette consumption was similar among smokers of each type of cigarette. Assuming that the intake of tar and nicotine is proportional to the inhaling index, the intake in either group of filter cigarette smokers would have been less than that in plain cigarette smokers. Among smokers of unventilated cigarettes, however, the intake would not have been much less.

  2. Inhaler technique maintenance: gaining an understanding from the patient's perspective.

    Ovchinikova, Ludmila; Smith, Lorraine; Bosnic-Anticevich, Sinthia

    2011-08-01

    The aim of this study was to determine the patient-, education-, and device-related factors that predict inhaler technique maintenance. Thirty-one community pharmacists were trained to deliver inhaler technique education to people with asthma. Pharmacists evaluated (based on published checklists), and where appropriate, delivered inhaler technique education to patients (participants) in the community pharmacy at baseline (Visit 1) and 1 month later (Visit 2). Data were collected on participant demographics, asthma history, current asthma control, history of inhaler technique education, and a range of psychosocial aspects of disease management (including adherence to medication, motivation for correct technique, beliefs regarding the importance of maintaining correct technique, and necessity and concern beliefs regarding preventer therapy). Stepwise backward logistic regression was used to identify the predictors of inhaler technique maintenance at 1 month. In total 145 and 127 participants completed Visits 1 and 2, respectively. At baseline, 17% of patients (n = 24) demonstrated correct technique (score 11/11) which increased to 100% (n = 139) after remedial education by pharmacists. At follow-up, 61% (n = 77) of patients demonstrated correct technique. The predictors of inhaler technique maintenance based on the logistic regression model (X(2) (3, N = 125) = 16.22, p = .001) were use of a dry powder inhaler over a pressurized metered-dose inhaler (OR 2.6), having better asthma control at baseline (OR 2.3), and being more motivated to practice correct inhaler technique (OR 1.2). Contrary to what is typically recommended in previous research, correct inhaler technique maintenance may involve more than repetition of instructions. This study found that past technique education factors had no bearing on technique maintenance, whereas patient psychosocial factors (motivation) did.

  3. Personal exposure to inhalable cement dust among construction workers.

    Peters, Susan; Thomassen, Yngvar; Fechter-Rink, Edeltraud; Kromhout, Hans

    2009-01-01

    Objective- A case study was carried out to assess cement dust exposure and its determinants among construction workers and for comparison among workers in cement and concrete production.Methods- Full-shift personal exposure measurements were performed and samples were analysed for inhalable dust and its cement content. Exposure variability was modelled with linear mixed models.Results- Inhalable dust concentrations at the construction site ranged from 0.05 to 34 mg/m(3), with a mean of 1.0 mg/m(3). Average concentration for inhalable cement dust was 0.3 mg/m(3) (GM; range 0.02-17 mg/m(3)). Levels in the ready-mix and pre-cast concrete plants were on average 0.5 mg/m(3) (GM) for inhalable dust and 0.2 mg/m(3) (GM) for inhalable cement dust. Highest concentrations were measured in cement production, particularly during cleaning tasks (inhalable dust GM = 55 mg/m(3); inhalable cement dust GM = 33 mg/m(3)) at which point the workers wore personal protective equipment. Elemental measurements showed highest but very variable cement percentages in the cement plant and very low percentages during reinforcement work and pouring. Most likely other sources were contributing to dust concentrations, particularly at the construction site. Within job groups, temporal variability in exposure concentrations generally outweighed differences in average concentrations between workers. 'Using a broom', 'outdoor wind speed' and 'presence of rain' were overall the most influential factors affecting inhalable (cement) dust exposure.Conclusion- Job type appeared to be the main predictor of exposure to inhalable (cement) dust at the construction site. Inhalable dust concentrations in cement production plants, especially during cleaning tasks, are usually considerably higher than at the construction site.

  4. Bronchospasm and anaphylactic shock following lidocaine aerosol inhalation in a patient with butane inhalation lung injury.

    Lee, Min-Young; Park, Kyong Ah; Yeo, So-Jeong; Kim, Shin-Hee; Goong, Hyeun-Jeong; Jang, An-Soo; Park, Choon-Sik

    2011-10-01

    Allergic reactions to local anesthetics are very rare and represent inhalation lung injury due to butane gas fuel. On the fifth day, he developed an asthmatic attack and anaphylactic shock immediately after lidocaine aerosol administration to prepare for bronchoscopy to confirm an acute inhalational lung injury diagnosis. Cardiopulmonary resuscitation was performed immediately after respiratory arrest, and the patient was admitted to the intensive care unit intubated and on a ventilator. He was extubated safely on the third post-cardiopulmonary resuscitation day. These observations suggest that aerosol lidocaine anesthesia may cause airway narrowing and anaphylactic shock. Practitioners should be aware of this potential complication. We report on this case with a brief review of the literature.

  5. Asthma, inhaled corticosteroid treatment, and growth.

    Ninan, T K; Russell, G

    1992-06-01

    To evaluate the effects on growth of inhaled corticosteroid treatment (ICT) and of the quality of control of asthma, height velocity was studied in 58 prepubertal children attending a specialist asthma clinic because of chronic asthma that was difficult to control. The height velocity standard deviation (SD) score was maximal when the asthma was well controlled both before (0.01) and after (-0.07) starting ICT. It was least when the asthma was poorly controlled both before (-1.50) and after (-1.55) starting ICT. The effectiveness of control correlated significantly with the height velocity SD score, both before and after ICT was started. No evidence was found that the administration of ICT has an adverse effect on growth.

  6. Toxic spongiform leucoencephalopathy after inhaling heroin vapour

    Weber, W.; Henkes, H.; Kuehne, D. [Klinik fuer Allgemeine Roentgendiagnostik und Neuroradiologie, Alfried-Krupp-Krankenhaus, Alfried Krupp Strasse 21, D-45117, Essen (Germany); Moeller, P.; Bade, K. [Neurologische Klinik, Knappschafts-Krankenhaus, D-45657 Recklinghausen (Germany)

    1998-06-02

    This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism. (orig.) With 2 figs., 2 tabs., 26 refs.

  7. Toxic spongiform leucoencephalopathy after inhaling heroin vapour

    Weber, W.; Henkes, H.; Kuehne, D.; Moeller, P.; Bade, K.

    1998-01-01

    This is a report of clinical, CT and MRI findings in a patient with toxic spongiform leucoencephalopathy after heroin ingestion. The disease is observed in drug addicts who inhale pre-heated heroin. The clinical onset, which usually occurs some days or even longer after the last heroin consumption, is characterized by a cerebellar syndrome. The cerebellar hemispheres, the cerebellar and cerebral peduncles and the pyramidal tract may be affected. Spongiform demyelination is the morphological substrate of the lesions, which are not contrast enhancing, hypodense on CT and hyperintense on T2-weighted MRI. The frequently perfect symmetry of the affection of functional systems points to a toxic and/or metabolic pathophysiological mechanism. (orig.)

  8. Pathology associated with inhaled plutonium in beagles

    Dagle, G.E.; Park, J.F.; Weller, R.E.; Ragan, H.A.; Stevens, D.L.

    1986-01-01

    The pathology associated with the inhalation of plutonium was studied in beagle dogs given a single exposure to aerosols of 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 . The temporal-spatial relationships between plutonium deposition and the development of lesions in dogs were evaluated up to 11 years, 8 years, or 5 years, respectively, after exposures, resulting in initial lung burdens ranging from ∼2 to ∼5500 nCi. Exposure of the lung to high dose levels produced a spectrum of progressively more severe morphological changes, ranging from radiation pneumonitis to fibrosis. Lung tumors occurred at exposure levels that did not result in early death from radiation pneumonitis or fibrosis. Bronchiolar-alveolar carcinomas, papillary adenocarcinomas, epidermoid carcinomas, and combined epidermoid and adenocarcinomas were observed. Sclerosing tracheobronchial lymphadenitis, radiation osteodystrophy, osteosarcoma, and hepatic adenomatous hyperplasia were the principal extrapulmonary lesions resulting from translocation of plutonium. 15 refs., 2 tabs

  9. Fatal accidental inhalation of brake cleaner aerosols.

    Veit, F; Martz, W; Birngruber, C G; Dettmeyer, R B

    2018-04-23

    Brake cleaner liquid is commonly used for cleaning of engines and motor parts. The commercially available products usually contain mainly volatile organic compounds. As a consequence brake cleaner evaporates fast and almost completely from the cleaned surface. This case report presents a fatal accidental inhalation of brake cleaner liquid aerosols due to the attempted cleaning of a boat engine. A 16year old boy was found lifeless in the engine compartment of a boat engine. In close proximity to the body, the police found cleanings wipes soaked with brake cleaner as well as a pump spray bottle filled with brake cleaner. Essentially the autopsy revealed a cerebral oedema with encephalomalacia, no coagulated blood as well as increased blood and tissue fluid content of the lung. Toxicological analysis revealed brake cleaner fluid in the lung, gastric content and heart blood. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Asthma and Adherence to Inhaled Corticosteroids

    Bårnes, Camilla Boslev; Ulrik, Charlotte Suppli

    2015-01-01

    Inhaled corticosteroids (ICS) are the cornerstone of maintenance asthma therapy. However, in spite of this, adherence to ICS remains low. The aim of this systematic literature review was to provide an overview of the current knowledge of adherence to ICS, effects of poor adherence, and means...... was found to be between 22 and 63%, with improvement up to and after an exacerbation. Poor adherence was associated with youth, being African-American, having mild asthma, ... prescribed fixed-combination therapy (ICS and long-acting β2 agonists). Good adherence was associated with higher FEV1, a lower percentage of eosinophils in sputum, reduction in hospitalizations, less use of oral corticosteroids, and lower mortality rate. Overall, 24% of exacerbations and 60% of asthma...

  11. Committed effective dose from thoron daughters inhalation

    Campos, M.P.; Pecequilo, B.R.S.

    2000-01-01

    Mankind's interest in natural radiation exposure levels has increased over the past fifty years and it is now recognized that the most significant contributors to human irradiation by natural sources are the short-lived decay products of radon ( 222 Rn) and thoron ( 220 Rn). Despite the thoron short half-life of 55 s, effective dose from inhalation of thoron an its progeny ( 212 Pb and 212 Bi) must be considered, owing to the high thorium background in countries like Brazil, China and India, for example. The indoor committed effective dose was assessed by air sampling at the thorium purification plant and the nuclear materials storage site of the Instituto de Pesquisas Energeticas e Nucleares; Sao Paulo, Brazil. A total of 21 glass fiber filter samples was analyzed by high resolution gamma ray spectrometry in order to obtain the 212 Pb and 212 Bi activities. The equilibrium equivalent concentration (EEC) varied from 0.3 Bq/m 3 to 6.8 Bq/m 3 for the storage site air samples and from 9.9 Bq/m 3 to 249.8 Bq/m 3 for the thorium purification plant air samples. As retention studies indicate a biological half-life of a few hours inhaled thoron progeny in the human lungs, the main fraction of the potential alpha energy (PAEC) deposited is absorbed in the lungs, meaning negligible to the effective dose the contribution of the dose in other times. The committed effective dose due thoron progeny was performed by compartimental analysis following the ICRP 66 lung compartimental model and ICRP 67 lead compartimental model. The values obtained varied from 0.03 mSv/a to 0.67 mSv/a for the storage site air samples and from 0.12 mSv/a to 6.00 mSv/a for the thorium purification plant air samples. (author)

  12. Radioaerosol inhalation lung scintigraphy in bronchial asthma

    Chiba, Takashi

    1993-01-01

    A study on obstructive changes in airways and mucociliary clearance in children and youth with bronchial asthma was performed. Radioaerosol inhalation lung scintigraphies using 99T c-human serum albumin (HSA) were applied to 50 children and youth with bronchial asthma. The deposition patterns of the radioaerosol and aerosol clearance curves were evaluated. Abnormal deposition patterns, which consisted of non-homogeneous distribution and/or hot spot formation, were likely to be seen in patients with asthmatic attacks at the time of measurements. However, a few asymptomatic patients also revealed abnormal deposition patterns. The deposition patterns were related to FEV 1.0 %, MMF, V 50 and V 25 , but especially to FEV 1.0 %. As an index of mucociliary clearance, β, the rate constant of the 99m Tc-HSA aerosol clearance curve, was introduced. β was significantly lower in patients with abnormal aerosol deposition patterns than in normal persons. β was also significantly lower in patients undergoing asthmatic attack at the time of the measurements than in asymptomatic patients. β correlated negatively with FEV 1.0 %, MMF, V 50 and V 25 , but especially with FEV 1.0 %. Although patients with long term affection or moderate-to-severe asthma tended to reveal abnormal deposition patterns and had low β values, these differences were not statistically significant. Radioaerosol inhalation lung scintigraphy with 99m Tc-HSA is useful for evaluating not only obstructive changes in the airways but also for evaluating mucociliary clearance in children with bronchial asthma. (author)

  13. Bromocriptine Mesylate Attenuates Amyotrophic Lateral Sclerosis: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Research in Japanese Patients.

    Eiichiro Nagata

    Full Text Available Bromocriptine mesylate (BRC, a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS Here we report a first in human trial in ALS.A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial.The trial was conducted between January 2009 and March 2012 on 36 Japanese ALS patients. A 12-week treatment with Riluzole observational period was followed by combined treatment (Riluzole + BRC; n = 29 or Riluzole + placebo; n = 7. The dosing commenced at 1.25 mg/day increasing in steps at two weeks intervals to a maximum of 15 mg/day. The efficacy of BRC was evaluated by comparing BRC and placebo groups upon completion of stepwise dosing at 14 weeks 2 points (1st endpoint and upon completion or discontinuation of the study (2nd endpoint of the dosing.Statistics analyses revealed a marginal BRC treatment efficacy with P≦20%to placebo by 1st and 2nd endpoint analysis. In the 1st endpoint analysis, BRC group was significantly effective on the scores of ALSAQ40-communicaton (P = 1.2%, eating and drinking (P = 2.2%, ALSFRS-R total (P = 17.6%, grip strength (P = 19.8% compared to the placebo group. In the 2nd endpoint analysis, differences between the scores of Limb Norris Scale (P = 18.3%, ALSAQ40-communication (P = 11.9%, eating and drinking (P = 13.6%, and neck forward-bent test (P = 15.4% of BRC group were detected between the two groups. There was no significant difference between the treatment groups for adverse events or serious drug reactions incidence.BRC sustains motoneuronal function at least in part through BRC treatment. Further analysis involving a Phase 2b or 3 clinical trial is required but BRC currently shows promise for ALS treatment.UMIN Clinical Trials UMIN000008527.

  14. Inhaled antibiotics for lower respiratory tract infections: focus on ciprofloxacin.

    Serisier, D J

    2012-05-01

    The administration of antibiotics by the inhaled route offers an appealing and logical approach to treating infectious respiratory conditions. Studies in the cystic fibrosis (CF) population have established the efficacy of this therapeutic concept and inhaled antibiotic therapy is now one of the pillars of management in CF. There are now a number of new inhaled antibiotic formulations that have shown impressive preliminary evidence for efficacy in CF and are commencing phase III efficacy studies. Translation of this paradigm into the non-CF bronchiectasis population has proven difficult thus far, apparently due to problems with tolerability of inhaled formulations. Inhaled versions of ciprofloxacin have shown good tolerability and microbiological efficacy in preliminary studies, suggesting that effective inhaled antibiotics are finally on the horizon for this previously neglected patient population. The increased use of long-term inhaled antibiotics for a wider range of non-CF indications presents risks to the broader community of greater antimicrobial resistance development that must be carefully weighed against any demonstrated benefits. Copyright 2012 Prous Science, S.A.U. or its licensors. All rights reserved.

  15. Inhaled Antibiotics in Reanimatology: Problem State and Development Prospects (Review

    A. N. Kuzovlev

    2017-01-01

    Full Text Available Nosocomial pneumonia is the second most common nosocomial infection in critical care units and most common in ALV patients (9—27%. The purpose of this literature review is to discuss the latest domestic and foreign body of evidence concerning the use of inhaled antibiotics в critical care. Search for domestic publications (literature reviews, observation studies, double blind randomized studies was carried out in elibrary.ru database, for foreign — in PubMed. Database for the period of yrs. 2005—2017. The following search enquiries were used: «inhaled antibiotics», «nosocomial pneumonia», «inhaled tobramycin», «inhaled colistin». The analysis includes 67 publications of yrs. 2007—2017 and 1 publication of yr. 2000. The literature review includes drug descriptions, contemporary capabilities of inhaled antibiotic therapy for nosocomial pneumonia, the advantages and drawbacks of this method of treatment. Special attention is focused on the use of inhaled aminoglycosides and inhaled colistin during nosocomial pneumonia in critical care units.

  16. Pharmacoeconomics of inhaled anesthetic agents: considerations for the pharmacist.

    Chernin, Eric L

    2004-10-15

    Types of economic analyses used for inhaled anesthetic agents, factors to consider in calculating the cost of inhaled anesthetics, limitations of pharmacoeconomic studies of these agents, and strategies for controlling inhaled anesthetic costs are discussed. Inhaled anesthetic agents comprise a substantial component of drug budgets. Calculation of the cost of administering an inhaled anesthetic should take into consideration the cost per mL, potency, waste, concentration and duration of gas delivery, fresh gas flow rate, molecular weight, and density. The use of newer inhaled anesthetic agents with low solubility in blood and tissue provides a more rapid recovery from anesthesia than older, more soluble agents, and also provides the same level of control of depth of anesthesia at a lower fresh gas flow rate and possibly a lower cost than older agents at a higher fresh gas flow rate. A more rapid recovery may facilitate fast-track recovery and yield cost savings if it allows the completion of additional surgical cases or allows a reduction in personnel overtime expenses. Interpretation of pharmacoeconomic studies of inhaled anesthetics requires an appreciation of the limitations in methodology and ability to extrapolate results from one setting to another. Pharmacists' efforts to reduce anesthetic waste and collaborate with anesthesiologists to improve the use of these agents can help contain costs, but improving scheduling and efficiency in the operating room has a greater potential to reduce operating room costs. Much can be done to control costs of anesthetic agents without compromising availability of these agents and patient care.

  17. Inhaled Steroids: First Line Treatment of Adult Asthma

    André Cartier

    1995-01-01

    Full Text Available Corticosteroids are the most potent inhaled anti-inflammatory drugs for asthma treatment. This paper reviews the clinical evidence supporting the early use of inhaled steroids in asthma as a first line treatment. Inhaled steroids can probably alter the course of asthma, especially in mild asthmatics. Once they have been shown to improve control of asthma and even if the need for beta2-agonists is virtually nil, their use should be continued at low doses (ie, equivalent to 400 to 500 μg of budesonide or beclomethasone for at least one year before attempting to reduce the dosage.

  18. Inhalation Toxicology Research Institute annual report 1987-1988

    Mauderly, J.L.; Mewhinney, J.A.; Bechtold, W.E.; Sun, J.D.; Coons, T.A.

    1988-12-01

    The mission of the Inhalation Toxicology Research Institute is to investigate the magnitude of human health effects that result from the inhalation of airborne materials at home, in the work place, or in the general environment. Diseases of the respiratory tract are major causes of suffering and death, and many of these diseases are directly related to the materials that people breath. The Institute's research is directed toward obtaining a better understanding of the basic biology of the respiratory tract and the mechanisms by which inhaled materials produce respiratory disease. Special attention is focused on studying the airborne materials released by various energy technologies, as well as those associated with national defense activities. The research uses a wide-ranging, comprehensive array of investigative approaches that are directed toward characterizing the source of the airborne material, following the material through its potential transformation in the air, identifying the mechanisms that govern its inhalation and deposition in the respiratory tract, and determining the fate of these inhaled materials in the body and the health effects they produce. The ultimate objectives are to determine the roles played by inhaled materials in the development of disease processes adn to estimate the risk they pose by inhaled materials in the development of disease processes and to estimate the risk they pose to humans who may be exposed to them. This report contains brief research papers that reflect the scope and recent findings of the Institute's research funded by the U.S. Department of Energy, principally through the Office of Health and Environmental Research. The papers are divided into topical sections. The first section, Characterization of Airborne Materials and Generation of Experimental Exposure Atmospheres, reflects the Institute's capabilities for fundamental aerosol research and the application of that expertise to toxicological studies. The second

  19. Inhalation Toxicology Research Institute annual report 1987-1988

    Mauderly, J L; Mewhinney, J A; Bechtold, W E; Sun, J D; Coons, T A [eds.

    1988-12-01

    The mission of the Inhalation Toxicology Research Institute is to investigate the magnitude of human health effects that result from the inhalation of airborne materials at home, in the work place, or in the general environment. Diseases of the respiratory tract are major causes of suffering and death, and many of these diseases are directly related to the materials that people breath. The Institute's research is directed toward obtaining a better understanding of the basic biology of the respiratory tract and the mechanisms by which inhaled materials produce respiratory disease. Special attention is focused on studying the airborne materials released by various energy technologies, as well as those associated with national defense activities. The research uses a wide-ranging, comprehensive array of investigative approaches that are directed toward characterizing the source of the airborne material, following the material through its potential transformation in the air, identifying the mechanisms that govern its inhalation and deposition in the respiratory tract, and determining the fate of these inhaled materials in the body and the health effects they produce. The ultimate objectives are to determine the roles played by inhaled materials in the development of disease processes adn to estimate the risk they pose by inhaled materials in the development of disease processes and to estimate the risk they pose to humans who may be exposed to them. This report contains brief research papers that reflect the scope and recent findings of the Institute's research funded by the U.S. Department of Energy, principally through the Office of Health and Environmental Research. The papers are divided into topical sections. The first section, Characterization of Airborne Materials and Generation of Experimental Exposure Atmospheres, reflects the Institute's capabilities for fundamental aerosol research and the application of that expertise to toxicological studies. The second

  20. Age of Inhalant First Time Use and Its Association to the Use of Other Drugs

    Ding, Kele; Chang, G. Andy; Southerland, Ron

    2009-01-01

    Inhalants are the 4th most commonly abused drugs after alcohol, tobacco, and marijuana. Although inhalants are often referred as Gateway Drugs this hypothesis is less examined. Using the 2003 National Survey on Drug Use and Health data, age of first time inhalant use was compared with the age of onset of other drugs among 6466 inhalant users who…

  1. The Chemo and the Mona: Inhalants, devotion and street youth in Mexico City

    Gigengack, R.A.

    2014-01-01

    This paper understands inhalant use – the deliberate inhalation of volatile solvents or glues with intentions of intoxication – as a socially and culturally constituted practice. It describes the inhalant use of young street people in Mexico City from their perspective (“the vicioso or inhalant

  2. The chemo and the mona : Inhalants, devotion and street youth in Mexico city

    Gigengack, Roy

    This paper understands inhalant use - the deliberate inhalation of volatile solvents or glues with intentions of intoxication - as a socially and culturally constituted practice. It describes the inhalant use of young street people in Mexico City from their perspective ("the vicioso or inhalant

  3. Deposition of inhaled uranium in Brazilian reference man

    Cardoso, Joaquim Carlos S.; Moraes, Jose Carlos T.B.

    1996-01-01

    Brazilian's morphometric and physiological parameters were selected for use in assessment of deposition of inhaled uranium. The assessment results were compared with estimates of deposition made with parameters recommended in ICRP 66. (author)

  4. Education on Correct Inhaler Technique in Pharmacy Schools ...

    Purpose: To investigate the effectiveness of a standard educational module on pharmacy students' inhaler technique .... found in the market next to a checklist showing its technique steps). ... educational strategies in this area. To ensure.

  5. Inhaled therapy for the management of perioperative pulmonary hypertension

    C A Thunberg

    2015-01-01

    Full Text Available Patients with pulmonary hypertension (PH are at high risk for complications in the perioperative setting and often receive vasodilators to control elevated pulmonary artery pressure (PAP. Administration of vasodilators via inhalation is an effective strategy for reducing PAP while avoiding systemic side effects, chiefly hypotension. The prototypical inhaled pulmonary-specific vasodilator, nitric oxide (NO, has a proven track record but is expensive and cumbersome to implement. Alternatives to NO, including prostanoids (such as epoprostenol, iloprost, and treprostinil, NO-donating drugs (sodium nitroprusside, nitroglycerin, and nitrite, and phosphodiesterase inhibitors (milrinone, sildenafil may be given via inhalation for the purpose of treating elevated PAP. This review will focus on the perioperative therapy of PH using inhaled vasodilators.

  6. Inhalant abuse of computer cleaner manifested as angioedema.

    Kurniali, Peter C; Henry, Letitia; Kurl, Rita; Meharg, Joseph V

    2012-01-01

    Inhalant abuse is the intentional inhalation of chemical vapors or volatile substance to achieve a euphoric effect. Although no statistical data are reported yet, inhalant abuse is potentially life-threatening and has resulted in a wide range of toxic effects such as central nervous system depression, seizures, aspiration, cardiac arrhythmia, asphyxiation, hypoxia, metabolic acidosis, and sudden death among others. We are reporting a 25-year-old white man who was brought to the emergency department after inhaling aerosolized computer-cleaning spray composed of difluoroethane. He was found to have marked upper and lower lip facial swelling consistent with angioedema. The patient also had a prolonged QT interval, mild inspiratory stridor, but no urticaria. In this case, we believe the difluoroethane-related angioedema represents either idiopathic or bradykinin-induced angioedema.

  7. Pharmacogenomics of inhaled corticosteroids and leukotriene modifiers : a systematic review

    Farzan, N.|info:eu-repo/dai/nl/412501929; Vijverberg, S.J.H.|info:eu-repo/dai/nl/325847460; Arets, H.G.M.; Raaijmakers, J.A.M.|info:eu-repo/dai/nl/072763299; van der Zee, A.H.|info:eu-repo/dai/nl/255164688

    BACKGROUND Pharmacogenetics studies of anti-inflammatory medication of asthma have expanded rapidly in recent decades, but the clinical value of their findings remains limited. OBJECTIVE To perform a systematic review of pharmacogenomics and pharmacogenetics of inhaled corticosteroids (ICS) and

  8. Inhaled Nanoparticles Accumulate at Sites of Vascular Disease

    Miller, Mark R; Raftis, Jennifer B; Langrish, Jeremy P; McLean, Steven G; Samutrtai, Pawitrabhorn; Connell, Shea P; Wilson, Simon; Vesey, Alex T; Fokkens, Paul H B; Boere, John A F; Krystek, Petra; Campbell, Colin J; Hadoke, Patrick W F; Donaldson, Ken; Cassee, Flemming R; Newby, David E; Duffin, Rodger; Mills, Nicholas L

    2017-01-01

    The development of engineered nanomaterials is growing exponentially, despite concerns over their potential similarities to environmental nanoparticles that are associated with significant cardiorespiratory morbidity and mortality. The mechanisms through which inhalation of nanoparticles could

  9. [Inhaled treatments in cystic fibrosis: what's new in 2013?].

    Dubus, J-C; Bassinet, L; Chedevergne, F; Delaisi, B; Desmazes-Dufeu, N; Reychler, G; Vecellio, L

    2014-04-01

    In the past few years some new inhaled drugs and inhalation devices have been proposed for the treatment of cystic fibrosis. Breath-controlled nebulizers allow increased pulmonary deposition, with a lower variability and a shorter delivery time. The new dry powder formulations of tobramycin, colistine and mannitol require a change in the inhalation technique which must be slow and deep. In the field of the inhaled mucolytic drugs, hypertonic saline and mannitol have an indication in some patients. With regard to antibiotics, dry-powder tobramycin and colistine can be substituted for the same drug delivered by nebulization. Nebulized aztreonam needs more studies to determine its place. These new treatments represent a definite advance for cystic fibrosis patients and need to be known by all practitioners. Their position in our therapeutic arsenal remains to be accurately defined. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  10. Inhaler Reminders Significantly Improve Asthma Patients' Use of Controller Medications

    ... controller medications Share | Inhaler reminders significantly improve asthma patients’ use of controller medications Published Online: July 22, ... the burden and risk of asthma, but many patients do not use them regularly. This poor adherence ...

  11. Inhaled Antibiotics in the Treatment of Nosocomial Pneumonia

    A. N. Kuzovlev

    2013-01-01

    Full Text Available Nosocomial pneumonia is the most common nosocomial infection in intensive care units. Rational antibiotic therapy is the basis for the treatment of nosocomial pneumonia. There is currently a challenge of the pathogens of nosocomial pneumonia being resistant to most of the antibiotics recommended for its treatment. Inhaled antibiotics used in combination with systemic drugs are an effective and safe treatment for nosocomial pneumonia. This review of literature characterizes the current possibilities of inhaled antibiotic therapy for nosocomial pneumonia in detail and describes medicaments and the advantages and disadvantages of this treatment option. Despite insufficient evidence in circumstances where the microorganisms are polyresistant and where the design of novel antibiotics shows no promise, the use of inhaled antibiotics is an important alternative in the treatment of severe nosocomial pneumonia caused by polyresistant gram-negative bacteria. Key words: nosocomial pneumonia, antibiotic therapy, inhaled antibiotics, resistance.

  12. Outcomes of cancer surgery after inhalational and intravenous anesthesia

    Soltanizadeh, Sinor; Degett, Thea H; Gögenur, Ismail

    2017-01-01

    Perioperative factors are probably essential for different oncological outcomes. This systematic review investigates the literature concerning overall mortality and postoperative complications after cancer surgery with inhalational (INHA) and intravenous anesthesia (TIVA). A search was conducted...

  13. Inhalation of Simulated Smog Affects Cardiac Function in Mice

    Rationale: The health effects of individual criteria air pollutants have been well investigated. Little is known about health effects of inhaled multi-pollutant mixtures that more realistically represent environmental exposures. The present study was designed to evaluate the card...

  14. Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease

    Sin, DD; Wu, L; Anderson, JA; Anthonisen, NR; Buist, AS; Burge, PS; Calverley, PM; Connett, JE; Lindmark, B; Pauwels, RA; Postma, DS; Soriano, JB; Szafranski, W; Vestbo, J

    2005-01-01

    Background: Clinical studies suggest that inhaled corticosteroids reduce exacerbations and improve health status in chronic obstructive pulmonary disease (COPD). However, their effect on mortality is unknown. Methods: A pooled analysis, based on intention to treat, of individual patient data from

  15. Radioaerosol Inhalation Lung Scan in Pulmonary Emphysema

    Jeon, Jeong Soo; Park, Yong Ha; Kyo, Chung Soo; Bahk, Yong Whee [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1990-07-15

    Perfusion and ventilation imagings of the lung are well established procedure for diagnosing pulmonary embolism, differentiation it from chronic obstructive lung disease, and making an early detection of chronic obstructive lung disease. To evaluate the usefulness of radioaerosol inhalation imaging (RII) in chronic obstructive lung disease, especially pulmonary emphysema, we analyzed RIIs of five normal adult non-smokers, five asymptomatic smokers (age 25-42 years with the mean 36), and 21 patients with pulmonary emphysema (age 59-78 years with the mean 67). Scintigrams were obtained with radioaerosol produced by a BARC nebuliser with 15 mCi of {sup 99m}Tc-phytate. Scanning was performed in the anterior, posterior, and lateral projections after five to 10-minute inhalation of the radioaerosol on sitting position. The scans were analyzed and correlated with the results of pulmonary function studies and chest radiographs. Also lung perfusion scan with {sup 99m}Tc-MAA was performed in 12 patients. In five patients, we performed follow-up scans for the evaluation of the effects of a bronchodilator. Based on the X-ray findings and clinical symptoms, pulmonary emphysema was classified into four types: centrilobular (3 patients), panlobular (4 patients), intermediate (10 patients), and combined (4 patients). RII findings were patternized according to the type, extent, and intensity of the aerosol deposition in the central bronchial and bronchopulmonary system and lung parenchyma. 10 controls, normal five non-smokers and three asymptomatic smokers revealed homogeneous parenchymal deposition in the entire lung fields without central bronchial deposition. The remaining two of asymptomatic smokers revealed mild central airway deposition. The great majority of the patients showed either central (9/21) or combined type (10/21) of bronchopulmonary deposition and the remaining two patients peripheral bronchopulmonary deposition. Parenchymal aerosol deposition in pulmonary

  16. Subchronic inhalation toxicity of gold nanoparticles

    Chung Yong

    2011-05-01

    Full Text Available Abstract Background Gold nanoparticles are widely used in consumer products, including cosmetics, food packaging, beverages, toothpaste, automobiles, and lubricants. With this increase in consumer products containing gold nanoparticles, the potential for worker exposure to gold nanoparticles will also increase. Only a few studies have produced data on the in vivo toxicology of gold nanoparticles, meaning that the absorption, distribution, metabolism, and excretion (ADME of gold nanoparticles remain unclear. Results The toxicity of gold nanoparticles was studied in Sprague Dawley rats by inhalation. Seven-week-old rats, weighing approximately 200 g (males and 145 g (females, were divided into 4 groups (10 rats in each group: fresh-air control, low-dose (2.36 × 104 particle/cm3, 0.04 μg/m3, middle-dose (2.36 × 105 particle/cm3, 0.38 μg/m3, and high-dose (1.85 × 106 particle/cm3, 20.02 μg/m3. The animals were exposed to gold nanoparticles (average diameter 4-5 nm for 6 hours/day, 5 days/week, for 90-days in a whole-body inhalation chamber. In addition to mortality and clinical observations, body weight, food consumption, and lung function were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry tests, and organ weights were measured. Cellular differential counts and cytotoxicity measurements, such as albumin, lactate dehydrogenase (LDH, and total protein were also monitored in a cellular bronchoalveolar lavage (BAL fluid. Among lung function test measurements, tidal volume and minute volume showed a tendency to decrease comparing control and dose groups during the 90-days of exposure. Although no statistically significant differences were found in cellular differential counts, histopathologic examination showed minimal alveoli, an inflammatory infiltrate with a mixed cell type, and increased macrophages in the high-dose rats. Tissue

  17. Radioaerosol Inhalation Lung Scan in Pulmonary Emphysema

    Jeon, Jeong Soo; Park, Yong Ha; Chung Soo Kyo; Bahk, Yong Whee

    1990-01-01

    Perfusion and ventilation imagings of the lung are well established procedure for diagnosing pulmonary embolism, differentiation it from chronic obstructive lung disease, and making an early detection of chronic obstructive lung disease. To evaluate the usefulness of radioaerosol inhalation imaging (RII) in chronic obstructive lung disease, especially pulmonary emphysema, we analyzed RIIs of five normal adult non-smokers, five asymptomatic smokers (age 25-42 years with the mean 36), and 21 patients with pulmonary emphysema (age 59-78 years with the mean 67). Scintigrams were obtained with radioaerosol produced by a BARC nebuliser with 15 mCi of 99m Tc-phytate. Scanning was performed in the anterior, posterior, and lateral projections after five to 10-minute inhalation of the radioaerosol on sitting position. The scans were analyzed and correlated with the results of pulmonary function studies and chest radiographs. Also lung perfusion scan with 99m Tc-MAA was performed in 12 patients. In five patients, we performed follow-up scans for the evaluation of the effects of a bronchodilator. Based on the X-ray findings and clinical symptoms, pulmonary emphysema was classified into four types: centrilobular (3 patients), panlobular (4 patients), intermediate (10 patients), and combined (4 patients). RII findings were patternized according to the type, extent, and intensity of the aerosol deposition in the central bronchial and bronchopulmonary system and lung parenchyma. 10 controls, normal five non-smokers and three asymptomatic smokers revealed homogeneous parenchymal deposition in the entire lung fields without central bronchial deposition. The remaining two of asymptomatic smokers revealed mild central airway deposition. The great majority of the patients showed either central (9/21) or combined type (10/21) of bronchopulmonary deposition and the remaining two patients peripheral bronchopulmonary deposition. Parenchymal aerosol deposition in pulmonary emphysema was

  18. Radioaerosol Inhalation Imaging in Bronchial Asthma

    Kim, Bum Soo; Park, Young Ha; Park, Jeong Mi; Chung, Myung Hee; Chung, Soo Kyo; Shinn, Kyung Sub; Bahk, Yong Whee

    1991-01-01

    Radioaerosol inhalation imaging (RII) has been used in radionuclide pulmonary studies for the past 20 years. The method is well accepted for assessing regional ventilation because of its usefulness, easy fabrication and simple application system. To evaluate its clinical utility in the study of impaired regional ventilation in bronchial asthma, we obtained and analysed RIIs in 31 patients (16 women and 15 men; age ranging 21-76 years) with typical bronchial asthma at the Department of Radiology, Kangnam St. Mary's Hospital, Catholic University Medical college, from January, 1988 to August, 1989. Scintiscans were obtained with radioaerosol produced by a HARC(Bhabha Atomic Research Center, India) nebulizer with 15 mCi of 99m Tc-phytate. The scanning was performed in anterior, posterior and lateral projections following 5-minute inhalation of radioaerosol on sitting position. The scans were analysed and correlated with the results of pulmonary function study and the findings of chest radiography. Fifteen patients had concomitant lung perfusion image with 99m Tc-MAA. Follow-up scans were obtained in 5 patients after bronchodilator therapy. 1 he patients were divided into (1) attack type (4 patients), (2) resistant type (5 patients), (3) remittent type (10 patients) and (4) bronchitic type (12 patients). Chest radiography showed hyperinflation, altered pulmonary vascularity, thickening of the bronchial wall and accentuation of hasal interstitial markings in 26 of the 31 patients. Chest radiographs were normal in the remaining 5 patients. Regardless of type, the findings of RII were basically the same, and characterized by the deposition of radioaerosol in the central parts or in the main respiratory air ways along with mottled nonsegmental ventilation defects in the periphery. Peripheral parenchymal defects were more extensive than that of expected findings from clinical symptoms, pulmonary function test and chest radiograph. Broomstick sign was present in 1.7 patients

  19. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle

    2013-01-01

    The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

  20. Acute chemical pneumonitis caused by nitric acid inhalation: case report

    Choe, Hyung Shim; Lee, In Jae; Ko, Eun Young; Lee, Jae Young; Kim, Hyun Beom; Hwang, Dae Hyun; Lee, Kwan Seop; Lee, Yul; Bae, Sang Hoon [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2003-06-01

    Chemical pneumonitis induced by nitric acid inhalation is a rare clinical condition. The previously reported radiologic findings of this disease include acute permeability pulmonary edema, delayed bronchiolitis obliterans, and bronchiectasis. In very few published rare radiologic reports has this disease manifested as acute alveolar injury; we report a case of acute chemical pneumonitis induced by nitric acid inhalation which at radiography manifested as bilateral perihilar consolidation and ground-glass attenuation, suggesting acute alveolar injury.

  1. A whiff of death: fatal volatile solvent inhalation abuse.

    Steffee, C H; Davis, G J; Nicol, K K

    1996-09-01

    Inhalation abuse of volatile solvents, previously known generically as "glue sniffing," is typically pursued by adolescents. A wide range of legal, easily obtained products containing volatile substances are available for abuse. We report two illustrative cases of fatal volatile substance abuse: gasoline sniffing in a 20-year-old man and aerosol propellant gas inhalation (aerosol air freshener) in a 16-year-old girl with underlying reactive airway disease. Although the ratio of deaths to nonfatal inhalation escapades is extremely low, volatile solvent abuse carries the risk of sudden death due to cardiac arrest after a dysrhythmia or vasovagal event, central nervous system respiratory depression, hypoxia and hypercapnia due to the techniques of inhalation, and other mechanisms. Investigation of the patient's substance abuse history, examination of the scene of death, and special toxicologic analyses are critical to identifying volatile substance inhalation abuse as the cause of death because anatomic autopsy findings will typically be nonspecific. Above all, physicians must suspect the diagnosis of volatile substance inhalation abuse, especially in any case of sudden death involving an otherwise healthy young person.

  2. Steam inhalation therapy: severe scalds as an adverse side effect

    Baartmans, Martin; Kerkhof, Evelien; Vloemans, Jos; Dokter, Jan; Nijman, Susanne; Tibboel, Dick; Nieuwenhuis, Marianne

    2012-01-01

    Background Steam inhalation therapy is often recommended in the treatment of a common cold. However, it has no proven benefit and may in fact have serious adverse side effects in terms of burn injuries. Aim To quantify the human and economic costs of steam inhalation therapy in terms of burn injury. Design and setting A prospective database study of all patients admitted to the burn centres (Beverwijk, Groningen, Rotterdam) and the hospital emergency departments in the Netherlands. Method Number and extent of burn injuries as a result of steam inhalation therapy were analysed, as well as an approximation made of the direct costs for their medical treatment. Results Annually, on average three people are admitted to in one of the Dutch burn centres for burns resulting from steam inhalation therapy. Most victims were children, and they needed skin grafting more often than adults. The total direct medical costs for burn centre and emergency department treatment were €115 500 (£93 000), emotional costs are not reflected. Conclusion As steam inhalation therapy has no proven benefit and the number and extent of complications of this therapy in terms of burn injury are significant, especially in children, steam inhalation therapy should be considered a dangerous procedure and not recommended anymore in professional guidelines and patient brochures. PMID:22781995

  3. Unsteady Particle Deposition in a Human Nasal Cavity during Inhalation

    Camby M.K. Se

    2010-12-01

    Full Text Available The present study investigates the deposition efficiency during the unsteady inhalation cycle by using Computational Fluid Dynamics (CFD. The unsteady inhalation profile was applied at the outlet of nasopharynx, which had a maximum flow rate of 40.3L/min which corresponds to an equivalent steady inhalation tidal volume flow rate of 24.6L/min. Aerodynamic particle sizes of 5μm and 20μm were studied in order to reflect contrasting Stokes numbered particle behaviour. Two particle deposition efficiencies in the nasal cavity versus time are presented. In general, the deposition of 5μm particles was much less than 20μm particles. The first 0.2 second of the inhalation cycle was found to be significant to the particle transport, since the majority of particles were deposited during this period (i.e. its residence time. Comparisons were also made with its equivalent steady inhalation flow rate which found that the unsteady inhalation produced lower deposition efficiency for both particle sizes.

  4. Cerebral blood flow (CBF) with 133Xe inhalation method

    Kusunoki, Tadaki; Masumura, Michio; Tamaki, Norihiko; Matsumoto, Satoshi; Yamashita, Hideyuki.

    1982-01-01

    The effects of CO 2 inhalation on the cerebral blood flow (CBF) were examined with 133 Xe inhalation method (Novo Inhalation Cerebrograph) on 9 normal peoples and 20 patients. Nine normal peoples were divided into 3 groups consisting of each 3 peoples, namely young age group, middle age group, and old age group. Each increased CBF (%) by CO 2 inhalation was 40 -- 44 in young age group, 36 -- 37 in middle age group, and 35 -- 36 in old age group in the blood flow of the first compartment (F 1 ), and 27 -- 28 in young age group, 30 -- 31 in middle age group and 23 -- 24 in old age group in the initial slope index (ISI). Each CO 2 reactivity factor (RF) was 5.5 -- 5.8 in young age group, 3.8 -- 4.0 in middle age group and 3.3 in old age group in F 1 , and 3.1 -- 3.2 in young age group, 2.0 -- 3.3 in middle age group, and 1.2 -- 1.3 in old age group in ISI. Twenty patients consisted of 15 patients of occlusive cerebrovascular disease, 2 patients of head injury, 2 patients of normal pressure hydrocephalus and one patient of subarachnoid hemorrhage. RF was abnormally lower than normal value in 5 patients in F 1 , but in 7 in ISI. Clinical benefits of CBF study during CO 2 inhalation with 133 Xe inhalation method were discussed. (author)

  5. Cariogenic Potential of Inhaled Antiasthmatic Drugs.

    Brigic, Amela; Kobaslija, Sedin; Zukanovic, Amila

    2015-08-01

    The organism of children with asthma is exposed to the effects of the disease but also the drugs for its treatment. Antiasthmatic drugs have different modes that promote the caries formation which varies according to their basic pharmacological composition. Namely, these drugs have a relatively low pH (5.5), can contain sweeteners such as lactose monohydrate in order to improve the drug taste or both. Frequent consumption of these inhalers in combination with reduced secretion of saliva increases the risk of caries. The study sample consisted of 200 patients, age from 7-14 years, divided into two groups: control group (n1 = 100) consisted of healthy children and the experimental group consisted of children suffering from asthma (n2 = 100). In both groups of respondents are determined the DMFT index, plaque index value and hygienic-dietary habits using the questionnaire. The subjects in the control group had significantly higher DMFT index than subjects in the experimental group (p = 0.004). It is determined that there are no significant differences in the values of plaque index (p>0.05). The effect of different diseases or medications from their treatment, diet and fermentable carbohydrates in the etiology of dental caries cannot be observed outside the living conditions of subjects, their social epidemiologic status, age, habits, oral hygiene, fluoride use, etc.

  6. Inhalational Steroids and Iatrogenic Cushing's Syndrome.

    A V, Raveendran

    2014-01-01

    Bronchial asthma (BA) and Allergic rhinitis (AR) are common clinical problems encountered in day to day practice, where inhalational corticosteroids (ICS) or intranasal steroids (INS) are the mainstay of treatment. Iatrogenic Cushing syndrome (CS) is a well known complication of systemic steroid administration. ICS /INS were earlier thought to be safe, but now more and more number of case reports of Iatrogenic Cushing syndrome have been reported, especially in those who are taking cytochrome P450 (CYP 450) inhibitors. Comparing to the classical clinical features of spontaneous Cushing syndrome, iatrogenic Cushing syndrome is more commonly associated with osteoporosis, increase in intra-ocular pressure, benign intracranial hypertension, aseptic necrosis of femoral head and pancreatitis, where as hypertension, hirsuitisum and menstrual irregularities are less common. Endocrine work up shows low serum cortisol level with evidence of HPA (hypothalamo-pituitary-adrenal) axis suppression. In all patients with features of Cushing syndrome with evidence of adrenal suppression always suspect iatrogenic CS. Since concomitant administration of cytochrome P450 inhibitors in patients on ICS/INS can precipitate iatrogenic CS, avoidance of CYP450 inhibitors, its dose reduction or substitution of ICS are the available options. Along with those, measures to prevent the precipitation of adrenal crisis has to be taken. An update on ICS-/INS- associated iatrogenic CS and its management is presented here.

  7. Seasonal inhalant insect allergy: Harmonia axyridis ladybug.

    Goetz, David W

    2009-08-01

    The exotic Asian lady beetle, Harmonia axyridis, has become a prominent cause of seasonal inhalant allergy (allergic rhinitis, asthma, and urticaria) in the last two decades in North America and Europe after being introduced into the environment as an agricultural pest-control predator. Seeking winter hibernation sites, ladybug swarms will invade human habitats in the fall. Large fall swarms and smaller spring dispersions produce corresponding peaks in ladybug allergy. Ladybug allergy prevalence in endemic areas has been reported as high as 10%. For some individuals ladybug allergy is their first expression of allergic disease. Exposures at home, work, school, and in other settings may be sensitizing. Ladybug hemolymph is the primary source of allergens. Har a 1 and Har a 2 major ladybug allergens have been characterized. 'Reflex bleeding' from tibiofemoral joints (for communication and during alarm) disperses these allergens. Ladybug skin testing should be routine in endemic areas. Avoidance continues to be the first step in treatment. Allergen vaccine therapy may be effective, but a commercial extract of H. axyridis is needed.

  8. Understanding pressurized metered dose inhaler performance.

    Ivey, James W; Vehring, Reinhard; Finlay, Warren H

    2015-06-01

    Deepening the current understanding of the factors governing the performance of the pressurized metered dose inhaler (pMDI) has the potential to benefit patients by providing improved drugs for current indications as well as by enabling new areas of therapy. Although a great deal of work has been conducted to this end, our knowledge of the physical mechanisms that drive pMDI performance remains incomplete. This review focuses on research into the influence of device and formulation variables on pMDI performance metrics. Literature in the areas of dose metering, atomization and aerosol evolution and deposition is covered, with an emphasis on studies of a more fundamental nature. Simple models which may be of use to those developing pMDI products are summarized. Although researchers have had good success utilizing an empirically developed knowledge base to predict pMDI performance, such knowledge may not be applicable when pursuing innovations in device or formulation technology. Developing a better understanding of the underlying mechanisms is a worthwhile investment for those working to enable the next generation of pMDI products.

  9. The optimization of iloprost inhalation under moderate flow of oxygen therapy in severe pulmonary arterial hypertension.

    Nakayama, Kazuhiko; Emoto, Noriaki; Tamada, Naoki; Okano, Mitsumasa; Shinkura, Yuto; Yanaka, Kenichi; Onishi, Hiroyuki; Hiraishi, Mana; Yamada, Shinichiro; Tanaka, Hidekazu; Shinke, Toshiro; Hirata, Ken-Ichi

    2018-01-01

    Inhaled iloprost efficiently improves pulmonary hemodynamics, exercise capacity, and quality of life in patients with pulmonary arterial hypertension (PAH). However, the process of inhalation is laborious for patients suffering from resting dyspnea. We describe a 75-year-old man with idiopathic PAH and a low gas transfer. Investigations excluded significant parenchymal lung disease and airflow obstruction (presuming FEV1/FVC ration > 70%). The patient struggled to complete iloprost inhalation due to severe dyspnea and hypoxemia. As such, we optimized the methods of oxygen supply from the nasal cannula to the trans-inhalator during the inhalation. We successfully shortened the inhalation duration that effectively reduced the laborious efforts required of patients. We also recorded pulmonary hemodynamics during inhalation of nebulized iloprost. This revealed significant hemodynamic improvement immediately following inhalation but hemodynamics returned to baseline within 2 hours. We hope that this optimization will enable patients with severe PAH to undergo iloprost inhalation.

  10. Pharmacokinetics and Bioavailability of Inhaled Esketamine in Healthy Volunteers.

    Jonkman, Kelly; Duma, Andreas; Olofsen, Erik; Henthorn, Thomas; van Velzen, Monique; Mooren, René; Siebers, Liesbeth; van den Beukel, Jojanneke; Aarts, Leon; Niesters, Marieke; Dahan, Albert

    2017-10-01

    Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained. A multicompartmental pharmacokinetic model was developed using population nonlinear mixed-effects analyses. The pharmacokinetic model consisted of three esketamine, two esnorketamine disposition and three metabolism compartments. The inhalation data were best described by adding two absorption pathways, an immediate and a slower pathway, with rate constant 0.05 ± 0.01 min (median ± SE of the estimate). The amount of esketamine inhaled was reduced due to dose-independent and dose-dependent reduced bioavailability. The former was 70% ± 5%, and the latter was described by a sigmoid EMAX model characterized by the plasma concentration at which absorption was impaired by 50% (406 ± 46 ng/ml). Over the concentration range tested, up to 50% of inhaled esketamine is lost due to the reduced dose-independent and dose-dependent bioavailability. We successfully modeled the inhalation of nebulized esketamine in healthy volunteers. Nebulized esketamine is inhaled with a substantial reduction in bioavailability. Although the reduction in dose-independent bioavailability is best explained by retention of drug and particle exhalation, the reduction in dose-dependent bioavailability is probably due to sedation-related loss of drug into the air.

  11. Inhaled Surfactant Therapy in Newborns in Artificial Lung Ventilation

    S. A. Perepelitsa

    2014-01-01

    Full Text Available Objective: to evaluate the efficiency of inhaled surfactant therapy in neonatal infants with respiratory failure.Subjects and methods. The trial enrolled 13 premature neonatal infants; their mean gestational age was 31.8±2.8 weeks and the birth weight was 1825±600.9 g. They had a oneminute Apgar score of 4.3±1.4. All the neonates needed mechanical ventilation (MV atbirth because the leading clinical sign was respiratory failure caused by acute intranatal hypoxia, neonatal amniotic fluid aspiration, respiratory distress syndrome (RDS, and cerebral ischemia. Curosurf was injected in a dose of 174.7±21 mg/kg in the infants with neonatal RDS at 35 minutes of life. All the babies included in the study were noted to have severe disease and prolonged MV. After stabilization of their status, the neonates received combination therapy involving surfactantBL inhalation to reduce the duration of MV. The dose of the agent was 75 mg. Results. After surfactantBL inhalation, effective spontaneous respiration occurred in 69.2% of the newborn infants; successful extubation was carried out. The median duration ofMV after surfactant BL inhalation was 22 hours (4—68 hours. There were no reintubated cases after inhalation therapy. Following surfactantBL inhalation, 4 (30.8% patients remained to be on MV as a control regimen; 3 of them had highfre quency MV. SurfactantBL inhalation made it possible to change the respiratory support regimen and to reduce MV parame ters in these babies. 

  12. Long-term effects of aluminium dust inhalation.

    Peters, Susan; Reid, Alison; Fritschi, Lin; de Klerk, Nicholas; Musk, A W Bill

    2013-12-01

    During the 1950s and 1960s, aluminium dust inhalation was used as a potential prophylaxis against silicosis in underground miners, including in Australia. We investigated the association between aluminium dust inhalation and cardiovascular, cerebrovascular and Alzheimer's diseases in a cohort of Australian male underground gold miners. We additionally looked at pneumoconiosis mortality to estimate the effect of the aluminium therapy. SMRs and 95% CI were calculated to compare mortality of the cohort members with that of the Western Australian male population (1961-2009). Internal comparisons on duration of aluminium dust inhalation were examined using Cox regression. Aluminium dust inhalation was reported for 647 out of 1894 underground gold miners. During 42 780 person-years of follow-up, 1577 deaths were observed. An indication of increased mortality of Alzheimer's disease among miners ever exposed to aluminium dust was found (SMR=1.38), although it was not statistically significant (95% CI 0.69 to 2.75). Rates for cardiovascular and cerebrovascular death were above population levels, but were similar for subjects with or without a history of aluminium dust inhalation. HRs suggested an increasing risk of cardiovascular disease with duration of aluminium dust inhalation (HR=1.02, 95% CI 1.00 to 1.04, per year of exposure). No difference in the association between duration of work underground and pneumoconiosis was observed between the groups with or without aluminium dust exposure. No protective effect against silicosis was observed from aluminium dust inhalation. Conversely, exposure to aluminium dust may possibly increase the risk of cardiovascular disease and dementia of the Alzheimer's type.

  13. Towards the optimisation and adaptation of dry powder inhalers.

    Cui, Y; Schmalfuß, S; Zellnitz, S; Sommerfeld, M; Urbanetz, N

    2014-08-15

    Pulmonary drug delivery by dry powder inhalers is becoming more and more popular. Such an inhalation device must insure that during the inhalation process the drug powder is detached from the carrier due to fluid flow stresses. The goal of the project is the development of a drug powder detachment model to be used in numerical computations (CFD, computational fluid dynamics) of fluid flow and carrier particle motion through the inhaler and the resulting efficiency of drug delivery. This programme will be the basis for the optimisation of inhaler geometry and dry powder inhaler formulation. For this purpose a multi-scale approach is adopted. First the flow field through the inhaler is numerically calculated with OpenFOAM(®) and the flow stresses experienced by the carrier particles are recorded. This information is used for micro-scale simulations using the Lattice-Boltzmann method where only one carrier particle covered with drug powder is placed in cubic flow domain and exposed to the relevant flow situations, e.g. plug and shear flow with different Reynolds numbers. Therefrom the fluid forces on the drug particles are obtained. In order to allow the determination of the drug particle detachment possibility by lift-off, sliding or rolling, also measurements by AFM (atomic force microscope) were conducted for different carrier particle surface structures. The contact properties, such as van der Waals force, friction coefficient and adhesion surface energy were used to determine, from a force or moment balance (fluid forces versus contact forces), the detachment probability by the three mechanisms as a function of carrier particle Reynolds number. These results will be used for deriving the drug powder detachment model. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Uncertainties on lung doses from inhaled plutonium.

    Puncher, Matthew; Birchall, Alan; Bull, Richard K

    2011-10-01

    In a recent epidemiological study, Bayesian uncertainties on lung doses have been calculated to determine lung cancer risk from occupational exposures to plutonium. These calculations used a revised version of the Human Respiratory Tract Model (HRTM) published by the ICRP. In addition to the Bayesian analyses, which give probability distributions of doses, point estimates of doses (single estimates without uncertainty) were also provided for that study using the existing HRTM as it is described in ICRP Publication 66; these are to be used in a preliminary analysis of risk. To infer the differences between the point estimates and Bayesian uncertainty analyses, this paper applies the methodology to former workers of the United Kingdom Atomic Energy Authority (UKAEA), who constituted a subset of the study cohort. The resulting probability distributions of lung doses are compared with the point estimates obtained for each worker. It is shown that mean posterior lung doses are around two- to fourfold higher than point estimates and that uncertainties on doses vary over a wide range, greater than two orders of magnitude for some lung tissues. In addition, we demonstrate that uncertainties on the parameter values, rather than the model structure, are largely responsible for these effects. Of these it appears to be the parameters describing absorption from the lungs to blood that have the greatest impact on estimates of lung doses from urine bioassay. Therefore, accurate determination of the chemical form of inhaled plutonium and the absorption parameter values for these materials is important for obtaining reliable estimates of lung doses and hence risk from occupational exposures to plutonium.

  15. Species difference in metabolism of inhaled butadiene

    Sabourin, P.J.; Dahl, A.R.; Bechtold, W.E.; Henderson, R.F.; Burka, L.T.

    1991-01-01

    Chronic exposure of B6C3F 1 mice and Sprague-Dawley rats to butadiene (BD) produced a very high incidence of cancer in mice while the incidence in rats was much lower with different tissues affected. Studies at this institute indicate that for equivalent exposures, the blood BD epoxide concentrations in mice are 5-fold higher than in rats and > 10-fold higher than in Cynomolgus monkeys. In this study, the profiles of urinary metabolites of butadiene were determined in Cynomolgus monkeys, F344/N rats, Sprague Dawley rats, B6C3F 1 mice and Syrian hamsters, species containing widely divergent hepatic epoxide hydrolase (EH) activities. Animals were exposed for 2 hr to 8,000 ppm [ 14 C]BD and 24-hr urine samples were analyzed for metabolites. Two major urinary metabolites were identified, N-acetyl-S-(-1(or 2)-3-butene-2(or 1)-ol)cysteine (1) and N-acetyl-S-(-4-butane-1,2-diol)cysteine (2). Monkeys exposed by inhalation produced primarily metabolite 2, while rodent species produced 1-4 times as much of 1 compared to 2. The ratio of 2/1 formation was related to the hepatic epoxide hydrolase activity in different species. The high 2/1 ratio in monkeys was consistent with the lower blood epoxide levels in this species. If BD metabolism by humans is similar to that in the monkey, exposure of humans to BD may result in lower tissue concentrations of reactive metabolites than an equivalent exposure of rodents. This has important implications for assessing the risk to humans of BD exposure based on rodent studies

  16. Exposure levels and determinants of inhalable dust exposure in bakeries.

    Burstyn, I; Teschke, K; Kennedy, S M

    1997-12-01

    The study's objectives were to measure full-shift exposure to inhalable dust in bakeries and define the determinants of full-shift exposure. Inhalable dust was measured gravimetrically. Ninety-six bakery workers, employed in seven different bakeries, participated in the study. Two side-by-side full-shift inhalable dust samples were obtained from each study participant on a single occasion. Samples were collected on 18 days selected at random. During the entire sampling period, bakers were observed and information on 14 different tasks was recorded at 15 min intervals. Other production characteristics were also recorded for each sampling day. These task and production variables were used in statistical modelling to identify significant predictors of exposure. The mean full-shift inhalable dust exposure was 8.2 mg/m3 (range: 0.1-110 mg/m3). A regression model explained 79% of the variability in exposure. The model indicated that tasks such as weighing, pouring and operating dough-brakers and reversible sheeters increased the exposure, while packing, catching and decorating decreased the exposure. Bread and bun production lines were associated with increased full-shift inhalable dust exposure, while cake production and substitution of dusting with the use of divider oil were associated with decreased exposure. Production tasks and characteristics are strong predictors of personal full-shift exposures to flour dust among bakers; these can be altered to reduce exposure levels.

  17. Methanol toxicity secondary to inhalant abuse in adult men.

    Wallace, Erik A; Green, Adam S

    2009-03-01

    The purpose of this report is to evaluate the presentation, treatment, and outcomes of adults with methanol toxicity from inhalation of carburetor cleaning fluid fumes. Retrospective chart review of adults with positive serum volatile screen for methanol and history of carburetor cleaning fluid fume inhalation. Sixteen patients were admitted 68 times. Eleven Native American patients accounted for 90% of admissions. Sixty-five cases presented with nausea/vomiting; 27 with intoxication or altered mental status; 21 with specific visual complaints. About 93% had a pH or=10 mOsm/L, and 69% had anion gap >16. Ten had an initial serum methanol level or=50 mg/dL. Six patients had a measurable serum ethanol level. Of the 29 patients with a methanol level of 20-49 mg/dL, 20 received intravenous antidote (ethanol or fomepizole); three received an antidote and hemodialysis. All who presented with a serum methanol level >or=50 mg/dL received intravenous ethanol or fomepizole. All visual symptoms resolved before discharge and all patients survived without sequelae. Discussion. This is the largest reported number of cases of methanol toxicity from the inhalation of carburetor cleaning fluid fumes and demonstrates a problem with recurrent abuse among some older Native American men. Intentional inhalation of methanol fumes may produce toxicity. Clinicians need to question patients, especially older Native American men, regarding the possible inhalation of carburetor cleaning fluid fumes in those who present with an unexplained metabolic anion gap acidosis.

  18. Accidental Cutaneous Burns Secondary to Salbutamol Metered Dose Inhaler

    Ashutosh Kale

    2010-01-01

    Full Text Available We report a case of accidental cutaneous burns caused by salbutamol metered dose inhaler. A 9-year-old boy underwent dental extraction at a children's hospital and was incidentally noted to have burn injuries on dorsum of both hands. On questioning, the boy revealed that a few days ago his 14-year-old brother, who is an asthmatic, playfully sprayed his salbutamol metered dose inhaler on the back of both his hands with the inhaler's mouth piece being in direct contact with the patient's skin. On examination, there was a rectangular area of erythema with superficial peeling on the dorsum of both hands, the dimensions of which exactly matched those of the inhaler's mouthpiece. It is possible that the injury could have been a chemical burn from the pharmaceutical/preservative/propellant aerosol or due to the physical effect of severe cooling of the skin or mechanical abrasive effect of the aerosol blasts or a combination of some or all the above mechanisms. This case highlights the importance of informing children and parents of the potentially hazardous consequences of misusing a metered dose inhaler.

  19. Titanium dioxide: inhalation toxicology and epidemiology.

    Hext, Paul M; Tomenson, John A; Thompson, Peter

    2005-08-01

    Titanium dioxide (TiO(2)) is manufactured worldwide in large quantities for use in a wide range of applications and is normally considered to be toxicologically inert. Findings of tumours in the lungs of rats exposed chronically to high concentrations of TiO(2), but not in similarly exposed mice or hamsters, suggest that the tumorigenic response may be a rat-specific phenomenon but nonetheless raises concerns for potential human health effects. With the limited toxicological understanding of species differences in response to inhaled TiO(2) and a similarly limited amount of epidemiological information with respect to TiO(2) exposure in the workplace, a consortium of TiO(2) manufacturers in Europe (under the European Chemistry Industry Council; CEFIC) and in North America (under the American Chemistry Council; ACC) initiated a programme of research to investigate inter-species differences as a result of exposure to TiO(2) and to conduct detailed epidemiological surveys of the major manufacturing sites. The toxicology studies exposed rats, mice and hamsters to pigment-grade TiO(2) (PG-TiO(2), 0, 10, 50 and 250 mg m(-3)) or ultrafine TiO(2) (UF-TiO(2), 0, 0.5, 2 and 10 mg m(-3)) for 90 days and the lung burdens and tissue responses were evaluated at the end of the exposure period and for up to 1 year after exposure. Results demonstrated clear species differences. Rats and mice had similar lung burdens and clearance rates while hamsters showed high clearance rates. At high lung particle burdens, rats showed a marked progression of histopathological lesions throughout the post-exposure period while mice and hamsters showed minimal initial lesions with recovery apparent during the post-exposure period. Lung neutrophil responses, a sensitive marker of inflammatory changes, reflected the development or recovery of the histopathological lesions. The use of surface area rather than gravimetric lung burden provided closer correlates of the burden to the biological effect

  20. Criteria for inhalation exposure systems utilizing concurrent flow spirometry

    Raabe, O.G.; Yeh, H.C.

    1974-01-01

    Principles are given for the design and operation of a new class of inhalation exposure systems utilizing concurrent flow spirometry (CFS), a simple method for providing realtime measurement of respiratory volumes and rates during inhalation exposure by mouth or nose of individual experimental animals or man to aerosols or gases. This technique is especially useful for inhalation exposure of larger experimental animals, such as horses, where whole-body plethysmography is usually impractical. Difficulties encountered with conventional exposure systems in maintenance of uniform aerosol or gas concentrations and prevention of large pressure excursions in the exposure chamber during breathing are obviated by systems utilizing the principles of concurrent flow spirometry. For illustration, two exposure units with CFS are described, one for exposure of Beagle dogs and one for ponies. (U.S.)

  1. Contribution of inhalation by food animals to man's ingestion dose

    Zach, R.

    1985-01-01

    Animals' inhalation (AI) pathway was evaluated for 57 radionuclides using infant dose predictions from the food-chain model LIMCAL. With ingestion transfer coefficients fMi to define transfer from the respiratory tract to milk, the AI pathway appeared to be insignificant compared to animals' plant ingestion, as implicitly assumed in most environmental assessment models for nuclear installations. Using ICRP Publication 30 respiratory clearance models for man to adjust ingestion transfer coefficients, animals' inhalation appeared to be important, particularly for some actinide radionuclides. The AI pathway also appeared to be significant relative to man's inhalation, especially for infants. The importance of the AI pathway varied greatly between radionuclides, and results strongly suggest that it cannot be ignored in environmental assessments. Until better data become available to implement this pathway fully, adjusted ingestion transfer coefficient values can be used for transfer from animals' respiratory tract to milk and other food products

  2. Pharmacokinetics of inhaled anesthetics in green iguanas (Iguana iguana).

    Brosnan, Robert J; Pypendop, Bruno H; Barter, Linda S; Hawkins, Michelle G

    2006-10-01

    To test the hypothesis that differences in anesthetic uptake and elimination in iguanas would counter the pharmacokinetic effects of blood:gas solubility and thus serve to minimize kinetic differences among inhaled agents. 6 green iguanas (Iguana iguana). Iguanas were anesthetized with isoflurane, sevoflurane, or desflurane in a Latin-square design. Intervals from initial administration of an anesthetic agent to specific induction events and from cessation of administration of an anesthetic agent to specific recovery events were recorded. End-expired gas concentrations were measured during anesthetic washout. Significant differences were not detected for any induction or recovery events for any inhalation agent in iguanas. Washout curves best fit a 2-compartment model, but slopes for both compartments did not differ significantly among the 3 anesthetics. Differences in blood:gas solubility for isoflurane, sevoflurane, and desflurane did not significantly influence differences in pharmacokinetics for the inhalation agents in iguanas.

  3. Sudden death due to inhalant abuse in youth: Case report

    Ramazan Akcan

    2010-06-01

    Full Text Available Intentional inhalation or abuse of volatile substances is a common public health problem all over the world. As these substances generate euphoria frequency of use among adolescents and young adults is increasing steadily. In cases using inhalants to achieve a euphoric state -without knowing possible consequences- sudden death may occurdue to acute cardio-pulmonary dysfunction.Here we present a case of sudden death of a nineteen-year-old female due to inhalation of volatile from butane containing lighter gas tube, with the findings of autopsy and death scene investigation.In the context of this case; it was aimed to draw attention to the risk of sudden death and steady increase of frequencyof volatile substance abuse among adolescents and young adults due to various psycho-social factors.

  4. Acute Respiratory Distress Syndrome (ARDS After Nitric Acid Inhalation

    Gülay Kır

    2014-12-01

    Full Text Available Lung injury resulting from inhalation of chemical products continues to be associated with high morbidity and mortality. Concentrated nitric acids are also extremely corrosive fuming chemical liquids. Fumes of nitric acid (HNO3 and various oxides of nitrogen such as nitric oxide (NO and nitrogen dioxide (NO2 may cause fatal illnesses such as severe pulmonary edema and acute respiratory distress syndrome (ARDS when inhaled. Intensive respiratory management including mechanical ventilation with positive end expiratory pressure (PEEP, inverse ratio ventilation, replacement of surfactant and extracorporeal membrane oxygenation (ECMO, steroids and n-acetylcysteine (NAC may improve survival. In this case report we present the diagnosis and successful treatment of a 57 years old male patient who developed ARDS following pulmonary edema due to nitric acid fumes inhalation.

  5. Inhalation scan using sup(81m)Kr-gas

    Kobayashi, Hidetoshi; Sasaki, Tsuneo; Senda, Kohei; Ohara, Ken; Kaii, Osamu

    1979-01-01

    Inhalation scan using sup(81m) Kr-gas was performed in the various pulmonary diseases, in order to examine the ventilatory function of the lung after the measurement of ratio of expiratory ratio in the normal and diseased lung field. Inhalation scan is applied to the various pulmonary diseases such as lung cancer, radiation pulmonary fibrosis and chronic obstructive pulmonary disease. In cases of lung cancer, there is disturbance of respiratory function at the site of lesion when compared to the remainder of the normal lung fields. In cases of chronic obstructive pulmonary disease, the inhalation scan is performed at three states such as pre-, in- and post-attack of the disease. During the asthma attack the respiratory function is disturbed considerably when compared to the pre- and post-attack states. In each pulmonary disease, the ratio of expiratory ratio is measured from the histogram and pulmonary function is evaluated. (author)

  6. Imagine the Superiority of Dry Powder Inhalers from Carrier Engineering

    Piyush Mehta

    2018-01-01

    Full Text Available Inhalation therapy has strong history of more than 4000 years and it is well recognized around the globe within every culture. In early days, inhalation therapy was designed for treatment of local disorders such as asthma and other pulmonary diseases. Almost all inhalation products composed a simple formulation of a carrier, usually α-lactose monohydrate orderly mixed with micronized therapeutic agent. Most of these formulations lacked satisfactory pulmonary deposition and dispersion. Thus, various alternative carrier’s molecules and powder processing techniques are increasingly investigated to achieve suitable aerodynamic performance. In view of this fact, more suitable and economic alternative carrier’s molecules with advanced formulation strategies are discussed in the present review. Furthermore, major advances, challenges, and the future perspective are discussed.

  7. Measurements and prediction of inhaled air quality with personalized ventilation

    Cermak, Radim; Majer, M.; Melikov, Arsen Krikor

    2002-01-01

    the room air) at flow rates ranging from less than 5 L/s up to 23 L/s. The air quality assessment was based on temperature measurements of the inhaled air and on the portion of the personalized air inhaled. The percentage of dissatisfied with the air quality was predicted. The results suggest......This paper examines the performance of five different air terminal devices for personalized ventilation in relation to the quality of air inhaled by a breathing thermal manikin in a climate chamber. The personalized air was supplied either isothermally or non-isothermally (6 deg.C cooler than...... that regardless of the temperature combinations, personalized ventilation may decrease significantly the number of occupants dissatisfied with the air quality. Under non-isothermal conditions the percentage of dissatisfied may decrease up to 4 times....

  8. A perspective on the developmental toxicity of inhaled nanoparticles

    Hougaard, Karin Sørig; Campagnolo, Luisa; Chavatte-Palmer, Pascale

    2015-01-01

    This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from the respirat......This paper aimed to clarify whether maternal inhalation of engineered nanoparticles (NP) may constitute a hazard to pregnancy and fetal development, primarily based on experimental animal studies of NP and air pollution particles. Overall, it is plausible that NP may translocate from...... the respiratory tract to the placenta and fetus, but also that adverse effects may occur secondarily to maternal inflammatory responses. The limited database describes several organ systems in the offspring to be potentially sensitive to maternal inhalation of particles, but large uncertainties exist about...

  9. Organ burdens and elimination rates of inhaled thorium and plutonium

    Unnikrishnan, K.; Murthy, K.B.S.; Sunta, C.M.

    1986-01-01

    For the purpose of interpreting observations from internal monitoring programmes, organ burdens and excretion rates resulting from inhalation of long-lived isotopes of plutonium and thorium have been calculated, on the basis of the ICRP model. Two types of inhalation, instantaneous (acute) and at a steady rate (chronic) are considered. The expected buildups of the burden in lungs, lymph nodes, bone, liver and other tissues, as well as the excretion rates, have been calculated for aerosol classes W and Y, and particle sizes of AMAD 1 μm and 6 μm. Further, in view of their use in selecting the periodicity of routine monitoring, theoretical results are also presented for the case of a total inhalation of 1 ALI in one year, instantaneously or at a constant rate. (author)

  10. Emergency department management of smoke inhalation injury in adults [digest].

    Otterness, Karalynn; Ahn, Christine; Nusbaum, Jeffrey; Gupta, Nachi

    2018-03-01

    Smoke inhalation injury portends increased morbidity and mortality in fire-exposed patients. Upper airway thermal burns, inflammation from lower airway irritants, and systemic effects of carbon monoxide and cyanide can contribute to injury. A standardized diagnostic protocol for inhalation injury is lacking, and management remains mostly supportive. Clinicians should maintain a high index of suspicion for concomitant traumatic injuries. Diagnosis is mostly clinical, aided by bronchoscopy and other supplementary tests. Treatment includes airway and respiratory support, lung protective ventilation, 100% oxygen or hyperbaric oxygen therapy for carbon monoxide poisoning, and hydroxocobalamin for cyanide toxicity. Due to its progressive nature, many patients with smoke inhalation injury warrant close monitoring for development of airway compromise. [Points & Pearls is a digest of Emergency Medicine Practice.].

  11. Particle exposure and inhaled dose during commuting in Singapore

    Tan, Sok Huang; Roth, Matthias; Velasco, Erik

    2017-12-01

    Exposure concentration and inhaled dose of particles during door-to-door trips walking and using motorized transport modes (subway, bus, taxi) are evaluated along a selected route in a commercial district of Singapore. Concentrations of particles smaller than 2.5 μm in size (PM2.5), black carbon, particle-bound polycyclic aromatic hydrocarbons, number of particles, active surface area and carbon monoxide have been measured in-situ using portable instruments. Simultaneous measurements were conducted at a nearby park to capture the background concentrations. The heart rate of the participants was monitored during the measurements as a proxy of the inhalation rate used to calculate the inhaled dose of particles. All measured metrics were highest and well above background levels during walking. No significant difference was observed in the exposure concentration of PM2.5 for the three motorized transport modes, unlike for the metrics associated with ultrafine particles (UFP). The concentration of these freshly emitted particles was significantly lower on subway trips. The absence of combustion sources, use of air conditioning and screen doors at station platforms are effective measures to protect passengers' health. For other transport modes, sections of trips close to accelerating and idling vehicles, such as bus stops, traffic junctions and taxi stands, represent hotspots of particles. Reducing the waiting time at such locations will lower pollutants exposure and inhaled dose during a commute. After taking into account the effect of inhalation and travel duration when calculating dose, the health benefit of commuting by subway for this particular district of Singapore became even more evident. For example, pedestrians breathe in 2.6 and 3.2 times more PM2.5 and UFP, respectively than subway commuters. Public buses were the second best alternative. Walking emerged as the worst commuting mode in terms of particle exposure and inhaled dose.

  12. Pentoxifylline does not alter the response to inhaled grain dust.

    Jagielo, P J; Watt, J L; Quinn, T J; Knapp, H R; Schwartz, D A

    1997-05-01

    Pentoxifylline (PTX) has been shown to reduce sepsis-induced neutrophil sequestration in the lung and inhibit endotoxin-mediated release of tumor necrosis factor-alpha (TNF-alpha). Previously, we have shown that endotoxin appears to be the principal agent in grain dust causing airway inflammation and airflow obstruction following grain dust inhalation. To determine whether PTX affects the physiologic and inflammatory events following acute grain dust inhalation, 10 healthy, nonsmoking subjects with normal airway reactivity were treated with PTX or placebo (PL) followed by corn dust extract (CDE) inhalation (0.08 mL/kg), using a single-blinded, crossover design. Subjects received PTX (1,200 mg/d) or PL for 4 days prior to CDE inhalation and 400 mg PTX or PL on the exposure day. Both respiratory symptoms and declines in FEV1 and FVC occurred following CDE exposure in both groups, but there were no significant differences in the frequency of symptoms or percent declines from baseline in the FEV1 and FVC at any of the time points measured in the study. Elevations in peripheral blood leukocyte and neutrophil concentrations and BAL total cell, neutrophil, TNF-alpha, and interleukin-8 concentrations were measured 4 h following exposure to CDE in both the PTX- and PL-treated subjects, but no significant differences were found between treatment groups. These results suggest that pretreatment with PTX prior to inhalation of CDE, in the doses used in this study, does not alter the acute physiologic or inflammatory events following exposure to inhaled CDE.

  13. Inhaled budesonide for treatment of recurrent wheezing in early childhood

    Bisgaard, H; Munck, Susanne; Nielsen, J P

    1990-01-01

    77 children, aged 11 to 36 months (mean 24) with moderately severe recurrent wheezing, were treated with budesonide pressurised aerosol 400 micrograms twice daily or placebo for 12 weeks in a double-blind, parallel-group trial. Aerosols were inhaled from a spacer with a facemask. Budesonide...... be ascribed to the active treatment. The findings indicate that young children below 3 years of age can inhale a pressurised aerosol from a spacer with a facemask. Use of topically active glucocorticosteroids with this simple device may reduce symptoms and distress in young children with moderately severe...

  14. Toxicity of inhaled alpha-emitting radionuclides - Status report

    Muggenburg, B.A.; Mewhinney, J.A.; Guilmette, R.A.; Gillett, N.A.; Diel, J.H.; Lundgren, D.L.; Hahn, F.F.; Boecker, B.B.; McClellan, R.O.

    1988-01-01

    The toxicity of inhaled alpha-emitting radionuclides is being investigated in a series of interrelated dose-response studies. Dogs, rodents, and nonhuman primates have been exposed to monodisperse or polydisperse aerosols of the oxides of 239 Pu, 238 Pu, 241 Am, or 244 Cm to measure the relative importance of average organ dose, local dose around particles, specific activity, chemical form, particle size, and number of particles inhaled to the development of biological effects. The influence of animal species, age at exposure, and pre-existing lung disease, as well as the effects of repeated exposure, are also being studied, because they may influence the toxicity of these radionuclides. (author)

  15. The reproductive dysfunction effects of gasoline inhalation in albino rats.

    Ugwoke, C C; Nwobodo, E D; Unekwe, P; Odike, M; Chukwumai, S T; Amilo, G

    2005-01-01

    Daily exposure to fuel vapour may pose significant health risk to exposed individuals. Fifteen each of male and female albino rats weighing between 110-230g were divided into test (10) and control (5) groups each. The test animals; were exposed to inhalation gasoline for one hour daily for twenty-one consecutive days. All animals were then bled and the serum levels of the reproductive hormones determined. The results showed significant [P inhalation gasoline exposure significantly [P < 0.05] lowers the levels of reproductive hormones in albino rats and may thus interfere with reproduction.

  16. Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

    Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

    2018-03-08

    Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma

  17. Inhalational and dermal exposures during spray application of biocides.

    Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

    2005-01-01

    Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a

  18. Efficacy of Oritavancin in a Murine Model of Bacillus anthracis Spore Inhalation Anthrax

    Heine, H. S; Bassett, J; Miller, L; Bassett, A; Ivins, B. E; Lehous, D; Arhin, F. F; Parr, Jr., T. R; Moeck, G

    2008-01-01

    The inhaled form of Bacillus anthracis infection may be fatal to humans. The current standard of care for inhalational anthrax postexposure prophylaxis is ciprofloxacin therapy twice daily for 60 days...

  19. Asthma Patients in US Overuse Quick-Relief Inhalers, Underuse Control Medications

    ... quick-relief inhalers, underuse control medications Share | Asthma patients in US overuse quick-relief inhalers, underuse control ... and uncontrolled asthma result in poor health outcomes. Patients with well-controlled asthma are at lower risk ...

  20. Effectiveness of the different methods of inhalation drugs delivery in children with bronchial asthma

    S.M. Nedelska

    2017-02-01

    Full Text Available Aim of the work — to evaluate the effectiveness of inhalation technique when using different types of inhalers (dry powder inhalers — Turbuhaler, Diskus, metered-dose inhalers, breath-actuated inhalers — Easyhaler. Materials and methods. 45 patients aged 6–17 years underwent the evaluation of inhalation technique accuracy with the use of In-Check-Dial — apparatus, which imitates the airway resistance that should be overcome during inspiration through different inhaler types, and measure inspiration velocity. Incidence of mistakes was studied in different age groups. Results. 80 % of children aged 6–7 years made mistakes while using Turbuhaler, 73.3 % — metered-dose inhaler, 60 % — Easyhaler. There were no mistakes in patients making inhalation by means of Diskhaler. 100 % of children aged 12–14 years incorrectly used metered-dose inhaler. Easyhaler was incorrectly used in 66.6 % of cases, Diskhaler — in 26.6 %. Among elder group, incidence of mistakes when making inhalations through Turbuhaler was lower — 40 % in 12–14-year-old group and 25 % — in 15–17-year-old (р < 0.05. Children of 15–17 years old are able to use Turbuhaler and Diskus (mistakes in 33.3 and 46.6 %, respectively. At the same time, none of the patients have done the correct inhalation by means of metered-dose inhaler, 93.3 % of the patients have mistakes when using Easyhaler. Conclusions. The incidence of mistakes depends on the age and inhaler type and reaches 26–100 %. Minimal quantity of mistakes is seen for Diskus (in all age groups, maxi­mal — for metered-dose inhaler. For the purpose of optimal inhaler choice in a child with bronchial asthma, it is advisable to measure the inspiratory flow with the help of In-Check-Dial before therapy administration.

  1. Experiment of aerosol-release time for a novel automatic metered dose inhaler

    Mingrong Zhang; Songhao Wang; Yu-Ching Yang

    2016-01-01

    The objective of this study was to evaluate the aerosol-release time in the development of a new automatic adapter for metered dose inhaler. With this device, regular manually operated metered dose inhalers become automatic. During the study, an inhalation simulator was designed and tested with the newly developed mechatronic system. By adjusting the volume and the pressure of the vacuum tank, most human inhalation waveforms were able to simulate. As an example, regular quick-deep and slow-de...

  2. Clinical effects of prior trastuzumab on combination eribulin mesylate plus trastuzumab as first-line treatment for human epidermal growth factor receptor 2 positive locally recurrent or metastatic breast cancer: results from a Phase II, single-arm, multicenter study

    Puhalla S

    2016-12-01

    Full Text Available Shannon Puhalla,1 Sharon Wilks,2 Adam M Brufsky,1 Joyce O’Shaughnessy,3 Lee S Schwartzberg,4 Erhan Berrak,5 James Song,5 Linda Vahdat6 1Department of Hematology and Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, 2Department of Hematology Oncology, US Oncology-Cancer Care Centers of South Texas, San Antonio, TX, 3Department of Medical Oncology, Texas Oncology-Baylor Charles A. Sammons Cancer Center US Oncology, Dallas, TX, 4Department of Hematology/Oncology, West Cancer Center, University of Tennessee Health Science Center, Memphis, TN, 5Department of Medical Affairs, Formerly of Eisai Inc., Woodcliff Lake, NJ, 6Department of Medicine, Weill Cornell Medical College, New York, NY, USA Abstract: Eribulin mesylate, a novel nontaxane microtubule dynamics inhibitor in the halichondrin class of antineoplastic drugs, is indicated for the treatment of patients with metastatic breast cancer who previously received ≥2 chemotherapy regimens in the metastatic setting. Primary data from a Phase II trial for the first-line combination of ­eribulin plus trastuzumab in human epidermal growth factor receptor 2 positive patients showed a 71% objective response rate and tolerability consistent with the known profile of these agents. Here, we present prespecified analyses of efficacy of this combination based on prior trastuzumab use. Patients received eribulin mesylate 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin [expressed as free base] intravenously on days 1 and 8 plus trastuzumab (8 mg/kg intravenously/cycle 1, then 6 mg/kg on day 1 of each 21-day cycle. Objective response rates, progression-free survival, and tolerability were assessed in patients who had and had not received prior adjuvant or neoadjuvant (neo/adjuvant trastuzumab treatment. Fifty-two patients (median age: 59.5 years received eribulin/trastuzumab for a median treatment duration of ~31 weeks; 40.4% (n=21 had been previously treated with neo/adjuvant trastuzumab prior to

  3. Design and application of a new modular adapter for laser diffraction characterization of inhalation aerosols

    de Boer, Anne; Gjaltema, D; Hagedoorn, P; Schaller, M; Witt, W; Frijlink, H W

    2002-01-01

    An inhaler adapter has been designed for the characterization of the aerosol clouds from medical aerosol generators such as nebulizers, dry powder inhalers (dpis) and metered dose inhalers (mdis) with laser diffraction technology. The adapter has a pre-separator, for separation of large particles

  4. Real-life characteristics of asthma inhaler device use in South Korea

    Wan Yau Ming, S.; Rhee, C.K.; Park, H.Y.; Yoo, K.H.; Kim, D.K.; Van Boven, J.F.; Price, D.; Park, H.S.

    2016-01-01

    Background and Aims: Historically, dry powder inhalers (DPIs) were considered to provide better airway distribution, easier identification of empty devices, and easier handling when compared to pressurized metered dose inhalers (pMDIs). Prior research into the major handling errors with inhaler

  5. Oxidative stress in a rat model of cotton smoke inhalation-induced ...

    Background: Smoke inhalation injury refers to airway and lung parenchyma injury and general chemical damage caused by inhaling toxic gases and substances. The aim of this study was to explore the oxidative stress mechanism of cotton smoke inhalation-induced pulmonary injury in a rat model. Materials and Methods: ...

  6. Inhalation Toxicology Research Institute annual report, October 1, 1983-September 30, 1984

    Guilmette, R.A.; Medinsky, M.A.

    1984-12-01

    The report describes research in the following areas: (1) aerosol generation and characterization; (2) deposition and fate of inhaled materials; (3) dose-response relationships for inhaled radionuclides; (4) dose-response relationships for inhaled chemical toxicants; and (5) biological factors that influence dose-response relationships. Project descriptions have been individually entered into the date base

  7. Brugada syndrome unmasked by accidental inhalation of gasoline vapors

    Kranjcec, Darko; Bergovec, Mijo; Rougier, Jean-Sébastien

    2007-01-01

    Loss-of-function mutations in the gene SCN5A can cause Brugada syndrome (BrS), which is an inherited form of idiopathic ventricular fibrillation. We report the case of a 46-year-old patient, with no previous medical history, who had ventricular fibrillation after accidental inhalation of gasoline...

  8. Exposure to inhalable, respirable, and ultrafine particles in welding fume.

    Lehnert, Martin; Pesch, Beate; Lotz, Anne; Pelzer, Johannes; Kendzia, Benjamin; Gawrych, Katarzyna; Heinze, Evelyn; Van Gelder, Rainer; Punkenburg, Ewald; Weiss, Tobias; Mattenklott, Markus; Hahn, Jens-Uwe; Möhlmann, Carsten; Berges, Markus; Hartwig, Andrea; Brüning, Thomas

    2012-07-01

    This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m(-3) for inhalable and 1.29 mg m(-3) for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m(-3)). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements welding fume. Concentrations were mainly predicted by the welding process and were significantly higher when local exhaust ventilation (LEV) was inefficient or when welding was performed in confined spaces. Substitution of high-emission techniques like FCAW, efficient LEV, and using PAPRs where applicable can reduce exposure to welding fume. However, harmonizing the different exposure metrics for UFP (as particle counts) and for the respirable or inhalable fraction of the welding fume (expressed as their mass) remains challenging.

  9. Inhaled Loxapine for Agitation in Intoxicated Patients: A Case Series.

    Roncero, Carlos; Ros-Cucurull, Elena; Palma-Álvarez, Raúl Felipe; Abad, Alfonso Carlos; Fadeuilhe, Christian; Casas, Miquel; Grau-López, Lara

    Episodes of agitation are frequent in intoxicated patients who have a substance use disorder, a psychiatric disorder or both (dual diagnosis). For managing the agitation, it is necessary to act promptly in a safe environment and addressing any underlying etiology. Inhaled loxapine improves symptoms of agitation in adults with psychiatric disorders (eg, schizophrenia) within 10 minutes of administration. Recently, some reports have documented the usefulness of loxapine in dual diagnoses patients with agitation. However, the efficacy of loxapine in intoxicated patients has not been deeply addressed. This report describes a case series of 12 patients (with addiction or dual disorder) who received inhaled loxapine for symptoms of psychomotor agitation during intoxication with different substances (eg, alcohol, cannabis, or cocaine) at 1 center in Spain. Data from 12 patients were reviewed, 5 patients were attended at the emergency room, 4 at the addiction and dual diagnosis unit, and 3 were treated during hospitalization for detoxification. All patients were under effects of substances. They had substance use disorder (including cannabis, cocaine, alcohol, hypnotics, and hallucinogens), and almost all (90%) presented 1 or more psychiatric disorders. One dose of inhaled loxapine was effective in 9 patients (75%), and in 3 patients, a second dose was required. Only mild dizziness was reported in 1 patient after the second dose. The acute agitation was effectively and quickly managed with inhaled loxapine in all intoxicated patients and enabled the appropriate clinical evaluation of the agitated state and the patient's management.

  10. Infant with Altered Consciousness after Cannabis Passive Inhalation

    Zarfin, Yehoshua; Yefet, Enav; Abozaid, Said; Nasser, Wael; Mor, Tamer; Finkelstein, Yoram

    2012-01-01

    We report on an infant who was admitted to hospital with severe neurological symptoms following passive inhalation of cannabis. To date, cannabis abuse has been described almost entirely in adolescents and adults. In early childhood, however, cannabis effects were almost exclusively discussed in the context of maternal prenatal exposure, and the…

  11. Therapeutic effects of co-inhaled roflumilast or formoterol and ...

    Purpose: To investigate the therapeutic effects of "inhaled" roflumilast and formoterol separately or combined with fluticasone on the ultrastructural airway changes in ovalbumin-induced asthmatic mice. Methods: The asthmatic mice were divided randomly into seven groups (n = 8): positive control, vehicle, and five treated ...

  12. Disposition and biological effect of inhaled 85Kr

    Willard, D.H.; Ballou, J.E.; Ragan, H.A.; Gandolfi, A.J.

    1978-01-01

    Half-lives of approximately 5, 30, and 100 min were obtained for whole-body clearance of inhaled 85 Kr in beagle dogs. Analysis showed the highest partition coefficients in lungs, bone marrow, and fat. Circulating blood elements were not lowered permanently after 85 Kr exposures

  13. Characteristics of peaks of inhalation exposure to organic solvents

    Preller, L.; Burstyn, I.; Pater, N. de; Kromhout, H.

    2004-01-01

    Objectives: To determine which exposure metrics are sufficient to characterize 'peak' inhalation exposure to organic solvents (OS) during spraying operations. Methods: Personal exposure measurements (n = 27; duration 5-159 min) were collected during application of paints, primers, resins and glues

  14. Evaluation and Management of Patients with Inhalation Injury

    1990-12-01

    PRUITT, Jr., M.D., WILLIAM G. CIOFFI, M.D., TAKESHI SHIMAZU, M.D. HISASHI IKEUCHI, M.D., AND ARTHUR D. MASON, Jr., M.D. D T CO ELECTE" Inhalation...215, 1988. Do you think that there is some common pathway here 22. Kimura , R., Traber, L., Herndon, D., et al: Ibuprofen reduces the where there is

  15. Inhalation toxicology of 241Am(NO3)3

    Ballou, J.E.; Gies, R.A.; Beasley, A.H.

    1980-01-01

    Inhaled 241 Am(NO 3 ) 3 was rapidly cleared from the lung (90% in 30 days) and translocated principally to skeleton. Although the estimated radiation dose to lung was twofold greater than the bone dose, the principal treatment-related lesion appeared to be osteosarcoma of the skeleton

  16. Solution of human respiratory tract model for chronic inhalation intake

    Nadar, Minal Y.; Singh, I.S.; Rao, D.D.; Pradeepkumar, K.S.

    2014-01-01

    For the radiation workers of fuel reprocessing and fuel fabrication plants, inhalation is one of the major routes of intake of internal contamination. In case of routine monitoring which would result in lung activity above detection limit, it is assumed that intake has occurred at the midpoint of monitoring interval so that underestimation introduced by the unknown time of intake is less than a factor of three. In the plants, chronic intakes of 239 Pu are possible if low levels of 239 Pu activities remain undetected. In ICRP-78, the retention values are given as a function of time for continuous chronic inhalation of 239 Pu at 1.71 Bq/day that would result in Committed Effective Dose (CED) of 20 mSv. Retention values (R) are not given for inhalation intake at any other rate. Therefore, Human Respiratory Tract Model (HRTM) is solved for continuous chronic inhalation at 1 Bq/day rate for type M compounds of 239 Pu to estimate R as a function of time. These values will be useful in estimating intake from lung activity measurements in case of chronic intakes

  17. INDOOR AIR QUALITY AND INHALATION EXPOSURE - SIMULATION TOOL KIT

    A Microsoft Windows-based indoor air quality (IAQ) simulation software package is presented. Named Simulation Tool Kit for Indoor Air Quality and Inhalation Exposure, or IAQX for short, this package complements and supplements existing IAQ simulation programs and is desi...

  18. Personal exposure to inhalable cement dust among construction workers.

    Peters, S.M.; Thomassen, Y.; Fechter-Rink, E.; Kromhout, H.

    2009-01-01

    Objective- A case study was carried out to assess cement dust exposure and its determinants among construction workers and for comparison among workers in cement and concrete production.Methods- Full-shift personal exposure measurements were performed and samples were analysed for inhalable dust and

  19. Inhalative cadmium effects in pregnant and fetal rats

    Prigge, E.

    1978-01-01

    Pregnant and non-pregnant rats were continuously exposed for 21 days to an aerosol containing 0.2, 0.4, and 0.6 mg cadmium/m/sup 3/ air. Pregnant and non-pregnant rats exposed to clean air served as controls. The aerosol was generated by an ultrasonic nebulizer and was carried into inhalation chambers. The median aerodynamic diameters were on the order of 0.6 ..mu..m. After inhalation of cadmium aerosols, serum iron levels were not lowered significantly in adult rats. A polycythaemic response of non-pregnant rats was observed due to a direct stimulatory effect of cadmium on erythropoiesis. Polycythaemia was less marked in pregnancy, presumably due to iron loss to placenta and fetus. Disturbances of pulmonary gas exchange or decreased plasma volumes were excluded as causative mechanisms of polycythaemia. In pregnant rats there was a marked dose dependent decrease of the activity of the alkaline phosphatase after cadmium inhalation, while there was no effect in exposed non-pregnant rats. This decreased enzyme activity, together with slowed growth rates and hemolytic effect indicate a higher sensitivity to cadmium in pregnancy. Proteinuria was not found in neither pregnant nor non-pregnant rats. Therefore, it is concluded that in this respect cadmium intoxication by inhalation does not resemble human toxemia of pregnancy, as discussed in the literature.

  20. the reproductive dysfunction effects of gasoline inhalation in albino

    admin

    exposure to inhalation gasoline, which generally saturate the ambient air of their workplaces. In this study, we challenged male and female albino rats with gasoline vapour and monitored the endocrine disruptive effects as part of a comprehensive study of the health risks faced by refinery workers in Nigeria. The ultimate.

  1. Inhaled Antibiotics for Gram-Negative Respiratory Infections

    Fraidenburg, Dustin R.; Scardina, Tonya

    2016-01-01

    SUMMARY Gram-negative organisms comprise a large portion of the pathogens responsible for lower respiratory tract infections, especially those that are nosocomially acquired, and the rate of antibiotic resistance among these organisms continues to rise. Systemically administered antibiotics used to treat these infections often have poor penetration into the lung parenchyma and narrow therapeutic windows between efficacy and toxicity. The use of inhaled antibiotics allows for maximization of target site concentrations and optimization of pharmacokinetic/pharmacodynamic indices while minimizing systemic exposure and toxicity. This review is a comprehensive discussion of formulation and drug delivery aspects, in vitro and microbiological considerations, pharmacokinetics, and clinical outcomes with inhaled antibiotics as they apply to disease states other than cystic fibrosis. In reviewing the literature surrounding the use of inhaled antibiotics, we also highlight the complexities related to this route of administration and the shortcomings in the available evidence. The lack of novel anti-Gram-negative antibiotics in the developmental pipeline will encourage the innovative use of our existing agents, and the inhaled route is one that deserves to be further studied and adopted in the clinical arena. PMID:27226088

  2. COMPARTMENTALIZATION OF THE INFLAMMATORY RESPONSE TO INHALED GRAIN DUST

    Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled grain dust. Previously, we found considerable production of these cytokines in the lower...

  3. Effects of Radon inhalation on physiology and disorders

    Yamaoka, Kiyonori; Komoto, Yoshiaki

    1998-01-01

    In the first study, we administered Radon (Rn) to rabbits by inhalation and examined changes in the lipid peroxide (thiobarbituric acid reacting substances; TBARS) level, superoxide dismutase (SOD) activity and membrane fluidity in various organs to clarify the therapeutic effects of Rn. In the second study, we sprayed Rn spring water of various concentrations to rabbits to make the animals inhale them, and examined mainly the responses of biogenic amine neurotransmitters for clarifying the effects of Rn inhalation in the neuronal transmitter system. In the third study, indications for treatment at the Misasa Hot Spring, a Rn producing radioactive spring, include hypertension, diabetes mellitus and pain. To clarify its mechanisms of action on these conditions, we evaluated dynamic changes in blood components such as vasoactive substances after Rn inhalation. Vasodilation, alleviation of diabetic symptoms and morphine-like analgesic effects were observed, suggesting that these changes constitute part of the mechanisms of the Rn spring therapy on the above conditions. (J.P.N.)

  4. Carbon monoxide inhalation induces headache in a human headache model

    Arngrim, Nanna; Schytz, Henrik Winther; Britze, Josefine

    2018-01-01

    , double-blind, placebo-controlled crossover design, 12 healthy volunteers were allocated to inhalation of CO (carboxyhemoglobin 22%) or placebo on two separate days. Headache was scored on a verbal rating scale from 0-10. We recorded mean blood velocity in the middle cerebral artery (VMCA) by transcranial...

  5. Desarrollo tecnológico de una formulación de dihidroergotoxina mesilato 0,3 mg/mL inyectable Technological development of an injectable formulation of dihydroergotoxine mesylate 0.3 mg/mL

    Anna Karelia Collado Coello

    2008-08-01

    Full Text Available Los vasodilatadores cerebrales y periféricos son un conjunto de medicamentos muy heterogéneo, que tienen en común la capacidad de producir vasodilatación cerebral o periférica por mecanismos muy diferentes.Dentro de ese grupo se encuentra el fármaco que le da razón a este artículo, la dihidroergotoxina mesilato el cual estimula el ritmo del electroencefalograma e incrementa la utilización de glucosa en el cerebro. Se desarrolló una formulación inyectable estéril compuesta por dihidroergotoxina mesilato polvo, y cantidad suficiente del vehículo acuoso envasada en ampolletas de 1 mL de capacidad. Se desarrolló y validó una técnica analítica por cromatografía líquida de alta resolución para estudiar la estabilidad de la formulación y determinar la fecha de vencimiento de esta. Se comprobó la calidad microbiológica de la preparación, y se logró un producto que cumple satisfactoriamente con todas las especificaciones establecidas para preparaciones estériles. La tecnología obtenida fue fácilmente escalable.Cerebral and peripheral vasodilators are a group of very heterogeneous drugs that have in common the capacity to produce cerebral or peripheral vasodilatation by different mechanisms. The drug that gave rise to this paper, dihydroergotoxine mesylate, is within this group. It stimulates the rhythm of the electroencephalogram and increases the utilization of glucose in the brain. A sterile injectable formulation composed of dihydroergotoxine mesylate powder and enough amount of aqueous vehicle was developed and bottled in ampoules of 1 mL. An analytical technique was developed and validated by high resolution liquid chromatography to study the stability of the formulation and to determine its expiration date. The quality of the microbiological preparation was proved, and a product that satisfactorily meets all the specifications established for sterile preparations was obtained. The technology obtained was easily scalable

  6. Aspergillus fumigatus viability drives allergic responses to inhaled conidia.

    Nayak, Ajay P; Croston, Tara L; Lemons, Angela R; Goldsmith, W T; Marshall, Nikki B; Kashon, Michael L; Germolec, Dori R; Beezhold, Donald H; Green, Brett J

    2018-04-13

    Aspergillus fumigatus induced allergic airway disease has been shown to involve conidial germination in vivo but the immunological mechanisms remain uncharacterized. A subchronic murine exposure model was used to examine the immunological mediators that are regulated in response to either culturable or non-culturable A. fumigatus conidia. Female B6C3F1/N mice were repeatedly dosed via inhalation with 1 x 105 viable or heat inactivated conidia (HIC), twice a week for 13 weeks (26 exposures). Control mice inhaled HEPA-filtered air. The influence of A. fumigatus conidial germination on the pulmonary immunopathological outcomes was evaluated by flow cytometry analysis of cellular infiltration in the airways, assessment of lung mRNA expression, and quantitative proteomics and histopathology of whole lung tissue. Repeated inhalation of viable conidia, but not HIC, resulted in allergic inflammation marked by vascular remodeling, extensive eosinophilia, and accumulation of alternatively activated macrophages (AAMs) in the murine airways. More specifically, mice that inhaled viable conidia resulted in a mixed TH1 and TH2 (IL-13) cytokine response. Recruitment of eosinophils corresponded with increased Ccl11 transcripts. Furthermore, genes associated with M2 or alternatively activated macrophage polarization (e.g. Arg1, Chil3 and Retnla) were significantly upregulated in viable A. fumigatus exposed mice. In mice inhaling HIC, CD4+ T cells expressing IFN-γ (TH1) dominated the lymphocytic infiltration. Quantitative proteomics of the lung revealed metabolic reprogramming accompanied by mitochondrial dysfunction and endoplasmic reticulum stress stimulated by oxidative stress from repetitive microbial insult. Our studies demonstrate that A. fumigatus conidial viability in vivo is critical to the immunopathological presentation of chronic fungal allergic disease. Copyright © 2018. Published by Elsevier Inc.

  7. Increasing Doses of Inhaled Corticosteroids Compared to Adding Long-Acting Inhaled beta(2)-Agonists in Achieving Asthma Control

    O'Byrne, Paul M.; Naya, Ian P.; Kallen, Anders; Postma, Dirkje S.; Barnes, Peter J.

    2008-01-01

    Background: Combination therapy with inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs), or treatment with high doses of ICSs alone improves asthma control when therapy with low-dose ICSs is not sufficient. However, it is not known which of these treatment options is more

  8. ‘Great ease and simplicity of action’: Dr Nelson’s Inhaler and the origins of modern inhalation therapy

    Barry Murnane

    2017-11-01

    Full Text Available Unveiled at the conclusion of a meeting of the Royal Medical and Chirurgical Society in 1861,[1] ‘Dr Nelson’s Improved Inhaler’ was one of the most important milestones in the genesis of reliable treatment of respiratory ailments in the modern era. Affordable and suitable for self-medication, the Dr Nelson’s Inhaler offered simple and reliable relief for patients with respiratory and pulmonary ailments. Conspicuous for its modesty and simplicity, it was one of the most widely produced, reproduced, and used inhalation devices in the final third of the nineteenth century. By reconstructing the ‘biography’ of the Nelson Inhaler, this article will attempt to sketch a network of medical and commercial interests and expertise in London which aligned in the 1860s to help establish inhalation as a popular, inexpensive, and trusted form of medical therapy for pulmonary ailments. This article will look at what connects physicians, apothecaries, and patients in the era: the medicines and technologies that were prescribed, made, bought, and which caused wellness, side-effects, and even death. This approach allows us to develop a narrative of respiratory illness as it was experienced by practitioners and patients alike.

  9. Development of a High Efficiency Dry Powder Inhaler: Effects of Capsule Chamber Design and Inhaler Surface Modifications

    Behara, Srinivas R.B.; Farkas, Dale R.; Hindle, Michael; Longest, P. Worth

    2013-01-01

    Purpose The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device. Methods DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices. Results The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI. Conclusions High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD 90%, and ED > 80%. PMID:23949304

  10. Development of a high efficiency dry powder inhaler: effects of capsule chamber design and inhaler surface modifications.

    Behara, Srinivas R B; Farkas, Dale R; Hindle, Michael; Longest, P Worth

    2014-02-01

    The objective of this study was to explore the performance of a high efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG) aerosol delivery based on changes to the capsule orientation and surface modifications of the capsule and device. DPIs were constructed by combining newly designed capsule chambers (CC) with a previously developed three-dimensional (3D) rod array for particle deagglomeration and a previously optimized EEG formulation. The new CCs oriented the capsule perpendicular to the incoming airflow and were analyzed for different air inlets at a constant pressure drop across the device. Modifications to the inhaler and capsule surfaces included use of metal dispersion rods and surface coatings. Aerosolization performance of the new DPIs was evaluated and compared with commercial devices. The proposed capsule orientation and motion pattern increased capsule vibrational frequency and reduced the aerosol MMAD compared with commercial/modified DPIs. The use of metal rods in the 3D array further improved inhaler performance. Coating the inhaler and capsule with PTFE significantly increased emitted dose (ED) from the optimized DPI. High efficiency performance is achieved for EEG delivery with the optimized DPI device and formulation combination producing an aerosol with MMAD  90%, and ED > 80%.

  11. Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

    Belinsky, S.A.; Hoover, M.D.; Bradley, P.L.

    1994-11-01

    This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database

  12. Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994

    Belinsky, S. A.; Hoover, M. D.; Bradley, P. L. [eds.

    1994-11-01

    This document from the Inhalation Toxicology Research Institute includes annual reports in the following general areas: (I) Aerosol Technology and Characterization of Airborne Materials; (II) Deposition, transport, and clearance of inhaled Toxicants; (III) Metabolism and Markers of Inhaled Toxicants; (IV) Carcinogenic Responses to Toxicants; (V) Mechanisms of carcinogenic response to Toxicants; (VI) Non carcinogenic responses to inhaled toxicants; (VII) Mechanisms of noncarcinogenic Responses to Inhaled Toxicants; (VIII) The application of Mathematical Modeling to Risk Estimates. 9 appendices are also included. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.

  13. Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig.

    Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn

    2015-05-01

    The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species. © 2014 Society for Risk Analysis.

  14. Inhaled corticosteroid metered-dose inhalers: how do variations in technique for solutions versus suspensions affect drug distribution?

    Robinson, Christie A; Tsourounis, Candy

    2013-03-01

    To assess the literature that evaluates how variations in metered-dose inhaler (MDI) technique affect lung distribution for inhaled corticosteroids (ICSs) formulated as MDI suspensions and solutions. PubMed (up to November 2012) and Cochrane Library (up to November 2012) were searched using the terms metered-dose inhalers, HFA 134a, Asthma/*drug therapy, and inhaled corticosteroids. In addition, reference citations from publications identified were reviewed. All articles in English from the data sources that assessed MDI technique comparing total lung distribution (TLD) of MDI solutions or suspensions formulated with ICSs were included in the review. Five relevant studies were identified. Five controlled studies compared how variations in MDI technique affect TLD for ICS MDI solutions with suspensions. MDI solutions resulted in greater TLD compared with larger particle MDI suspensions. Delayed or early inspiration upon device actuation of MDI solutions resulted in less TLD than coordinated actuation, but with a 3- to 4-times greater TLD than MDI suspensions inhaled using a standard technique. A sixth study evaluated inspiratory flow rates (IFR) for small, medium, and large particles. Rapid and slow IFRs resulted in similar TLD for small particles, while far fewer particles reached the airways with medium and large particles at rapid, rather than slow, IFRs. Based on the literature evaluated, standard MDI technique should be used for ICS suspensions. ICS MDI solutions can provide a higher average TLD than larger-particle ICS suspensions using standard technique, discoordinated inspiration and medication actuation timing, or rapid and slow IFRs. ICS MDI solutions allow for a more forgiving technique, which makes them uniquely suitable options for patients with asthma who have difficultly with MDI technique.

  15. A review of the value of innovation in inhalers for COPD and asthma.

    Virchow, Johann Christian; Akdis, Cezmi A; Darba, Josep; Dekhuijzen, Richard; Hartl, Sylvia; Kobelt, Gisela; Roger, Albert; Simoens, Steven; Toumi, Mondher; Woodhouse, Ben; Plich, Adam; Torvinen, Saku

    2015-01-01

    Appropriate use of inhaled therapies for asthma and chronic obstructive pulmonary disease (COPD) is critical to ensuring good patient outcomes, efficient use of healthcare resources and limiting the effects of high-morbidity. The appropriate choice of inhaler and active therapy, incorporating patient preferences, can help improve treatment adherence and long-term outcomes. Despite this, many current inhalers are non-intuitive to use, and require extensive training. In this review, an expert panel considers the evidence for the use of inhaler devices in management of COPD and asthma. The panel also evaluates the value of innovation in inhaler technologies, which optimise the use of existing molecules from a clinical, economic and societal perspective. The panel conclusion is that there remains a substantial unmet need in inhaler technology and that innovation in inhaler devices can provide real-world health benefits to patients. Furthermore, we recommend that these innovations should be supported by healthcare systems through appropriate pricing and reimbursement mechanisms.

  16. How to match the optimal currently available inhaler device to an individual child with asthma or recurrent wheeze

    van Aalderen, Wim M.; Garcia-Marcos, Luis; Gappa, Monika; Lenney, Warren; Pedersen, Søren; Dekhuijzen, Richard; Price, David

    2015-01-01

    Inhaled medications are the cornerstone of treatment in early childhood wheezing and paediatric asthma. A match between patient and device and a correct inhalation technique are crucial for good asthma control. The aim of this paper is to propose an inhaler strategy that will facilitate an inhaler

  17. Ease-of-use preference for the ELLIPTA® dry powder inhaler over a commonly used single-dose capsule dry powder inhaler by inhalation device-naïve Japanese volunteers aged 40 years or older

    Komase Y

    2014-12-01

    Full Text Available Yuko Komase,1 Akimoto Asako,2 Akihiro Kobayashi,3 Raj Sharma4 1Department of Respiratory Internal Medicine, St Marianna University School of Medicine, Yokohama City Seibu Hospital, Yokohama, Kanagawa, Japan; 2MA Respiratory Department, Development and Medical Affairs Unit, GlaxoSmithKline KK, Tokyo, Japan; 3Biomedical Data Sciences Department, GlaxoSmithKline KK, Tokyo, Japan; 4Global Respiratory Franchise Medical Department, GSK, Stockley Park, UK Background: In patients receiving inhaled medication, dissatisfaction with and difficulty in using the inhaler can affect treatment adherence. The incidence of handling errors is typically higher in the elderly than in younger people. The aim of the study was to assess inhaler preference for and handling errors with the ELLIPTA® dry powder inhaler (DPI, (GSK, compared with the established BREEZHALER™, a single-dose capsule DPI (Novartis, in inhalation device-naïve Japanese volunteers aged ≥40 years. Methods: In this open-label, nondrug interventional, crossover DPI preference study comparing the ELLIPTA DPI and BREEZHALER, 150 subjects were randomized to handle the ELLIPTA or BREEZHALER DPIs until the point of inhalation, without receiving verbal or demonstrative instruction (first attempt. Subjects then crossed over to the other inhaler. Preference was assessed using a self-completed questionnaire. Inhaler handling was assessed by a trained assessor using a checklist. Subjects did not inhale any medication in the study, so efficacy and safety were not measured. Results: The ELLIPTA DPI was preferred to the BREEZHALER by 89% of subjects (odds ratio [OR] 70.14, 95% confidence interval [CI] 33.69–146.01; P-value not applicable for this inhaler for ease of use, by 63% of subjects (OR 2.98, CI 1.87–4.77; P<0.0001 for ease of determining the number of doses remaining in the inhaler, by 91% for number of steps required, and by 93% for time needed for handling the inhaler. The BREEZHALER was

  18. The use of multiple respiratory inhalers requiring different inhalation techniques has an adverse effect on COPD outcomes

    Bosnic-Anticevich S

    2016-12-01

    Full Text Available Sinthia Bosnic-Anticevich,1 Henry Chrystyn,2 Richard W Costello,3,4 Myrna B Dolovich,5 Monica J Fletcher,6 Federico Lavorini,7 Roberto Rodríguez-Roisin,8 Dermot Ryan,9,10 Simon Wan Yau Ming,2 David B Price2,11 1Woolcock Institute of Medical Research, School of Medical Sciences, University of Sydney and Sydney Local Health District, Sydney, NSW, Australia; 2Observational and Pragmatic Research Institute Pte Ltd, Singapore; 3RCSI Medicine, Royal College of Surgeons, 4RCSI Education & Research Centre, Beaumont Hospital, Beaumont, Dublin, Ireland; 5Department of Medicine, Respirology, McMaster University, ON, Canada; 6Education for Health, Warwick, UK; 7Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 8Respiratory Institute, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain; 9Optimum Patient Care, Cambridge, 10Centre for Population Health Sciences, University of Edinburgh, Edinburgh, 11Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: Patients with COPD may be prescribed multiple inhalers as part of their treatment regimen, which require different inhalation techniques. Previous literature has shown that the effectiveness of inhaled treatment can be adversely affected by incorrect inhaler technique. Prescribing a range of device types could worsen this problem, leading to poorer outcomes in COPD patients, but the impact is not yet known. Aims: To compare clinical outcomes of COPD patients who use devices requiring similar inhalation technique with those who use devices with mixed techniques. Methods: A matched cohort design was used, with 2 years of data from the Optimum Patient Care Research Database. Matching variables were established from a baseline year of follow-up data, and two cohorts were formed: a “similar-devices cohort” and a “mixed-devices cohort”. COPD-related events were recorded during an outcome year of follow-up. The primary outcome measure was an

  19. Effect of novel inhaler technique reminder labels on the retention of inhaler technique skills in asthma: a single-blind randomized controlled trial.

    Basheti, Iman A; Obeidat, Nathir M; Reddel, Helen K

    2017-02-09

    Inhaler technique can be corrected with training, but skills drop off quickly without repeated training. The aim of our study was to explore the effect of novel inhaler technique labels on the retention of correct inhaler technique. In this single-blind randomized parallel-group active-controlled study, clinical pharmacists enrolled asthma patients using controller medication by Accuhaler [Diskus] or Turbuhaler. Inhaler technique was assessed using published checklists (score 0-9). Symptom control was assessed by asthma control test. Patients were randomized into active (ACCa; THa) and control (ACCc; THc) groups. All patients received a "Show-and-Tell" inhaler technique counseling service. Active patients also received inhaler labels highlighting their initial errors. Baseline data were available for 95 patients, 68% females, mean age 44.9 (SD 15.2) years. Mean inhaler scores were ACCa:5.3 ± 1.0; THa:4.7 ± 0.9, ACCc:5.5 ± 1.1; THc:4.2 ± 1.0. Asthma was poorly controlled (mean ACT scores ACCa:13.9 ± 4.3; THa:12.1 ± 3.9; ACCc:12.7 ± 3.3; THc:14.3 ± 3.7). After training, all patients had correct technique (score 9/9). After 3 months, there was significantly less decline in inhaler technique scores for active than control groups (mean difference: Accuhaler -1.04 (95% confidence interval -1.92, -0.16, P = 0.022); Turbuhaler -1.61 (-2.63, -0.59, P = 0.003). Symptom control improved significantly, with no significant difference between active and control patients, but active patients used less reliever medication (active 2.19 (SD 1.78) vs. control 3.42 (1.83) puffs/day, P = 0.002). After inhaler training, novel inhaler technique labels improve retention of correct inhaler technique skills with dry powder inhalers. Inhaler technique labels represent a simple, scalable intervention that has the potential to extend the benefit of inhaler training on asthma outcomes. REMINDER LABELS IMPROVE INHALER TECHNIQUE: Personalized

  20. Carbon dioxide inhalation treatments of neurotic anxiety. An overview.

    Wolpe, J

    1987-03-01

    A lucky chance more than 30 years ago revealed the remarkable efficacy of single inhalations of high concentrations of carbon dioxide in eliminating or markedly reducing free-floating anxiety. The reduction of anxiety lasts for days, weeks, or longer--well beyond the persistence of carbon dioxide in the body. The effects are explicable on the hypothesis that free-floating anxiety is anxiety conditioned to continuously present sources of stimulation, such as background noise or the awareness of space or time, and that the anxiety response habit is weakened when the anxiety is inhibited by the competition of responses that carbon dioxide induces. More recently, it has become apparent that inhalations of carbon dioxide, applied in a different manner, are effective in overcoming maladaptive anxiety responses to specific stimuli, e.g., social stimuli. The substance is also proving to be a valuable resource in the treatment of the common variety of panic attacks.

  1. Role of inhaled amphotericin in allergic bronchopulmonary aspergillosis

    I S Sehgal

    2014-01-01

    Full Text Available Allergic bronchopulmonary aspergillosis (ABPA is an immunological pulmonary disorder caused by immune reactions mounted against the ubiquitous fungus Aspergillus fumigatus. The disease clinically manifests with poorly controlled asthma, hemoptysis, systemic manifestations like fever, anorexia and weight loss, fleeting pulmonary opacities and bronchiectasis. The natural course of the disease is characterized by repeated episodes of exacerbations. Almost 30-40% of the patients require prolonged therapy, which currently consists of corticosteroids and anti-fungal azoles; both these agents have significant adverse reactions. Amphotericin B administered via the inhaled route can achieve a high concentration in the small airways with minimal systemic side-effects. Nebulized amphotericin B has been used in the management of invasive pulmonary aspergillosis. The aim of this review is to study the utility of inhaled amphotericin in ABPA.

  2. Polymer degradation and ultrafine particles - Potential inhalation hazards for astronauts

    Ferin, J.; Oberdoerster, G.

    1992-01-01

    To test the hypothesis that exposure to ultrafine particles results in an increased interstiatilization of the particles which is accompanied by an acute pathological inflammation, rats were exposed to titanium dioxide (TiO2) particles by intratracheal instillation and by inhalation. Both acute intratracheal instillation and subchronic inhalation studies on rats show that ultrafine TiO2 particles access the pulmonary interstitium to a larger extent than fine particles and that they elicit an inflammatory response as indicated by PMN increase in lavaged cells. The release of ultrafine particles into the air of an enclosed environment from a thermodegradation event or from other sources is a potential hazard for astronauts. Knowing the mechanisms of action is a prerequisite for technical or medical countermeasures.

  3. The inhalation of radioactive materials as related to hand contamination

    Bailey, J.C.; Rohr, R.C.

    1953-09-15

    Tests performed to determine the hazard associated with the inhalation of radioactive materials as the result of smoking with contaminated hands indicate that for dry uranium compounds adhering to the palmar surfaces of the hands, approximately 1.0% of the material may be transferred to a cigarette, and that of this approximately 0.2% may appear in the smoke which is inhaled. Most of the contamination originally placed in a cigarette was found in the ash, and only 11% of the material was not recovered following burning; approximately half of this loss may be attributed to normal losses inherent in the analytical process, the recovery efficiency for which was found by supplementary experiments to be 95%.

  4. Inhaled insulin for controlling blood glucose in patients with diabetes

    Bernard L Silverman

    2008-01-01

    Full Text Available Bernard L Silverman1, Christopher J Barnes2, Barbara N Campaigne3, Douglas B Muchmore31Alkermes, Inc, Cambridge, MA, USA; 2i3 Statprobe, Ann Arbor, MI; 3Eli Lilly and Company, Indianapolis, IN, USAAbstract: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.Keywords: diabetes, inhaled insulin, cardiovascular disease, blood glucose

  5. Nasal Filters For Relief From Atopic Dermatitis Caused by Inhalants

    J S Pasricha

    1989-01-01

    Full Text Available Nasal filter is a simple device consisting of a net mounted in a frame made to fit inside the nostrils. These filters thus are not visible from outside. If a person uses the nasal filters the .u particulate material from the air that the person breathes gets removed and in case the person is allergic to an inhalant antigen, he stops having the allergic symptoms. We tried nasal filters on two females patients aged 32 and 7 years respectively, having topics dermatitis the age of I year, caused by an inhalant (indicated by seasonal aggravations, and spontaneous recovery during brief visits to other towns. Unrig a follow-up of 2 1/2 and 2 years respectively, both the patients experienced almost 80-90% relief from the dermatitis and required only animal treatment.

  6. Practical Considerations for Dysphonia Caused by Inhaled Corticosteroids

    Galván, César A.; Guarderas, Juan Carlos

    2012-01-01

    Inhaled corticosteroid (ICS) therapy has become standard in the treatment of asthma. A common local adverse effect of ICS therapy is dysphonia, which has been reported to affect 5% to 58% of patients. Although causes of dysphonia associated with ICS therapy have been underinvestigated, it may result from deposition of an active ICS in the oropharynx during administration, which then causes myopathy or a mucosal effect in the laryngopharynx. Use of ICS should be considered during any evaluation of dysphonia. We recommend using the lowest effective dosage of ICS, administering medication with a spacer, gargling, rinsing the mouth and washing the face after inhalation, and washing the spacer. If dysphonia develops despite these interventions, ICS use should be suspended until symptoms resolve, provided that asthma control is not compromised. PMID:22958993

  7. Inhalant-Abuse Myocarditis Diagnosed by Cardiac Magnetic Resonance.

    Dinsfriend, William; Rao, Krishnasree; Matulevicius, Susan

    2016-06-01

    Multiple reports of toxic myocarditis from inhalant abuse have been reported. We now report the case of a 23-year-old man found to have toxic myocarditis from inhalation of a hydrocarbon. The diagnosis was made by means of cardiac magnetic resonance imaging with delayed enhancement. The use of cardiac magnetic resonance to diagnose myocarditis has become increasingly common in clinical medicine, although there is not a universally accepted criterion for diagnosis. We appear to be the first to document a case of toxic myocarditis diagnosed by cardiac magnetic resonance. In patients with a history of drug abuse who present with clinical findings that suggest myocarditis or pericarditis, cardiac magnetic resonance can be considered to support the diagnosis.

  8. Intake of radioactivity by inhalation, in buildings after nuclear incidents

    Brenk, H.D.

    1987-01-01

    Risk studies so far assumed that in case of a nuclear incident, the exposure of persons through inhalation proceeds in free air by direct intake of contaminated ambient air. In reality, however, about 80 p.c. of the population is indoors, and there is a considerable delay of room air contamination in comparison with free air contamination. The radionuclides are deposited on indoor surfaces (such as walls, windows, furniture, etc.), and in air-conditioning systems on the filters. This contamination is somewhat regularly removed through cleaning or filter exchange, which reduces the contamination of room air, and then also the radiation exposure by inhalation. The reducing effect can be enhanced by such simple measures as closing doors and windows in time, and switching the air-conditioning system to recirculating regime, followed by enhanced fresh air supply at a later time. (orig./HP) [de

  9. Inhaled beclomethasone in pregnant asthmatic women--a systematic review.

    de Aguiar, M M; da Silva, H J; Rizzo, J Â; Leite, D F B; Silva Lima, M E P L; Sarinho, E S C

    2014-01-01

    The aim of this study was to systematically review the safety and efficacy of inhaled beclomethasone for asthma treatment in pregnant women. We performed a systematic review in Medline, LILACS and SciELO electronic databases in December 2012. A total of 3433 articles were found by using the keywords asthma, pregnancy and beclomethasone. Among these, 1666 were from Medline, via PubMed, and 1767 were from LILACS and SciELO. Nine of these articles were selected. Only one paper suggested an increased foetal risk for congenital malformations, and one other for offspring endocrine and metabolic disturbances. Data are mostly reassuring, supporting the use of glucocorticoid inhalants during pregnancy, and we found no evidence of inferiority in relation to efficacy and safety of beclomethasone compared to other drugs used in pregnant asthmatic women. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

  10. Role of inhalation in exposure to polychlorinated biphenyls (PCBs)

    Monarca, S.; Dominici, L.; Fatigoni, C.

    2007-01-01

    Polychlorinated biphenyls (PCBs) are a group of aromatic compounds consisting of a biphenyl variously chlorinated. Industrial production of PCBs started in 1929 and stopped in the second half of the '70s in USA and in the late 80's and 90's in Europe. PCBs are ubiquitous pollutants. The way of human exposure to PCBs is a matter of discussion. Scientific data show that the greater exposure occurs through diet. However, other available data suggest a not marginal role of the inhalation exposure. The sources of PCBs to which population are exposed depend on the amount of redistribution of these compounds released in the environment. The aim of this work is to highlight numerous studies proving that the intake of PCBs by inhalation cannot be neglected, in particular in heavily industrialized areas and where the concentration of PCBs in the environmental matrices is particularly high

  11. Toxicity of inhaled alpha-emitting radionuclides - Status report

    Muggenburg, B A; Mewhinney, J A; Guilmette, R A; Gillett, N A; Diel, J H; Lundgren, D L; Hahn, F F; Boecker, B B; McClellan, R O

    1988-12-01

    The toxicity of inhaled alpha-emitting radionuclides is being investigated in a series of interrelated dose-response studies. Dogs, rodents, and nonhuman primates have been exposed to monodisperse or polydisperse aerosols of the oxides of {sup 239}Pu, {sup 238}Pu, {sup 241}Am, or {sup 244}Cm to measure the relative importance of average organ dose, local dose around particles, specific activity, chemical form, particle size, and number of particles inhaled to the development of biological effects. The influence of animal species, age at exposure, and pre-existing lung disease, as well as the effects of repeated exposure, are also being studied, because they may influence the toxicity of these radionuclides. (author)

  12. Lung cancer and inhaled uranium ore dust in rats

    Mitchel, R.E.J.; Jackson, J.S.

    1997-01-01

    Using a nose only inhalation system, 187 nine week old male Sprague-Dawley rats were exposed to two different concentrations of natural uranium ore dust aerosol (44% U) without significant radon content. Inhalation exposures averaged about 4.2 h/day, 5 days/week for 65 weeks at which point lung uranium burdens in the two groups averaged 0.9 and 1.9 mg/g dry weight. Animals (63) exposed to the air stream without dust served as controls. After inhalation exposure ceased, the rats were allowed to live for their natural lifetime, a maximum of about 900 days after the start of dust inhalation. Lung uranium burdens were measured at the time of death of each animal. Lung burdens were found to decline exponentially after dust inhalation ceased, and the rate of decline was independent of the initial lung burden. All lungs were examined at necropsy and histologically for lung tumors. Lung tumors of lung origin were observed in both exposed groups and in the control group. The frequency of primary malignant lung tumors was 0.016, 0.175 and 0.328 and primary non-malignant lung tumors 0.016, 0.135 and 0.131 in the control low and high aerosol exposed groups respectively. Absorbed dose to the lung was calculated for each animal in the study. The average maximum doses for all the animals exposed to the low or high concentration of dust aerosol were 0.87 Gy and 1.64 Gy respectively. The average risk of malignant lung tumors from inhaled natural uranium ore dust was therefore about 0.20 tumors/animal/Gy. For animals with lung tumors, the average doses were 0.98 and 1.90 in the exposed groups. In both exposed groups, the frequency of primary malignant or non-malignant lung tumors was significantly greater than in the control group (p < 0.02) and the frequency of primary malignant lung tumors in the two exposed group were significantly different from each other (p = 0.05). The frequency of primary lung tumors (malignant and non-malignant) was calculated as a function of dose

  13. Individual monitoring program for occupational exposures to radionuclides by inhalation

    Piechowski, J.; Menoux, B.

    1985-01-01

    Individual monitoring of exposure to radioactive products is carried out when there is a risk of significant internal contamination. In its publications 26 and 35 the International Commission on Radiological Protection has given recommendations on the monitoring programs. Besides, the metabolic models developed in publication 30 have allowed to establish retention and excretion functions for some radionuclides after intake by inhalation in the adult man. These have been published in the report CEA-R--5266. Considering these data and taking into account the practical problems that occur in the course of surveillance of workers, programs of individual monitoring for contamination by inhalation are proposed. These programs for routine and special monitoring have been developed for the most common radionuclides involved in the nuclear industry [fr

  14. [Etiology of combined inhalational hydrocyanic acid and carbon monoxide poisoning].

    Sigrist, T; Dirnhofer, R

    1979-01-01

    A young man was found dead in a kitchen, that was partly burnt. Autopsy revealed, as cause of death, a combined intoxication following inhalation of carbon monoxide and hydrocyanic acid. Own investigations on the pyrolysis of pieces of furniture found in the kitchen (plastic plates containing melamine and plates containing formaldehyde) showed, that hydrocyanic acid was liberated through combustion of such substances and inhaled by the victim. The poisoning picture is discussed, and discussion includes especially considerations on the peculiar sensitivity of the brain toward the action of hydrocyanic acid and the relative insensitivity of the heart muscle. It is thought that the cause of such sensitivity difference lies in the physiological differences of the intracellular energy production. Finally the dangers of combustion gases developing from burning plastic materials are reemphasized.

  15. Practice makes perfect: self-reported adherence a positive marker of inhaler technique maintenance.

    Azzi, Elizabeth; Srour, Pamela; Armour, Carol; Rand, Cynthia; Bosnic-Anticevich, Sinthia

    2017-04-24

    Poor inhaler technique and non-adherence to treatment are major problems in the management of asthma. Patients can be taught how to achieve good inhaler technique, however maintenance remains problematic, with 50% of patients unable to demonstrate correct technique. The aim of this study was to determine the clinical, patient-related and/or device-related factors that predict inhaler technique maintenance. Data from a quality-controlled longitudinal community care dataset was utilized. 238 patients using preventer medications where included. Data consisted of patient demographics, clinical data, medication-related factors and patient-reported outcomes. Mixed effects logistic regression was used to identify predictors of inhaler technique maintenance at 1 month. The variables found to be independently associated with inhaler technique maintenance using logistic regression (Χ 2 (3,n = 238) = 33.24, p < 0.000) were inhaler technique at Visit 1 (OR 7.1), device type (metered dose inhaler and dry powder inhalers) (OR 2.2) and self-reported adherent behavior in the prior 7 days (OR 1.3). This research is the first to unequivocally establish a predictive relationship between inhaler technique maintenance and actual patient adherence, reinforcing the notion that inhaler technique maintenance is more than just a physical skill. Inhaler technique maintenance has an underlying behavioral component, which future studies need to investigate. BEHAVIORAL ELEMENT TO CORRECT LONG-TERM INHALER TECHNIQUES: Patients who consciously make an effort to perfect asthma inhaler technique will maintain their skills long-term. Elizabeth Azzi at the University of Sydney, Australia, and co-workers further add evidence that there is a strong behavioral component to patients retaining correct inhaler technique over time. Poor inhaler technique can limit asthma control, affecting quality of life and increasing the chances of severe exacerbations. Azzi's team followed 238 patients to

  16. ''Inhalation lung imaging with radioactive aerosols and gases''

    Taplin, G.V.; Chopra, S.K.

    1977-01-01

    Lung imaging procedures, performed after the inhalation of /sup 99m/Tc labeled aerosols, 133 Xe and /sup 81m/Kr gases, were used to visualize the sites of airway obstruction and regional abnormalities of ventilatory function in normal volunteers, patients with obstructive airway disease, and pulmonary embolism suspects. Comparisons were made of three methods regarding their functional significance, diagnostic merits, and limitations. A new nebulizer-radioaerosol delivery system is described

  17. Inhalation Exposure Input Parameters for the Biosphere Model

    K. Rautenstrauch

    2004-09-10

    This analysis is one of 10 reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. Inhalation Exposure Input Parameters for the Biosphere Model is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling, and the plan for development of the biosphere abstraction products for TSPA, as identified in the Technical Work Plan for Biosphere Modeling and Expert Support (BSC 2004 [DIRS 169573]). This analysis report defines and justifies values of mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of ERMYN to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception.

  18. Inhaled Loxapine for Agitation in Intoxicated Patients: A Case Series

    Roncero, Carlos; Ros-Cucurull, Elena; Palma-Álvarez, Raúl Felipe; Abad, Alfonso Carlos; Fadeuilhe, Christian; Casas, Miquel; Grau-López, Lara

    2017-01-01

    Objectives Episodes of agitation are frequent in intoxicated patients who have a substance use disorder, a psychiatric disorder or both (dual diagnosis). For managing the agitation, it is necessary to act promptly in a safe environment and addressing any underlying etiology. Inhaled loxapine improves symptoms of agitation in adults with psychiatric disorders (eg, schizophrenia) within 10 minutes of administration. Recently, some reports have documented the usefulness of loxapine in dual diagn...

  19. Radon inhalations applied in the treatment of eye fundus diseases

    Ogielska, E.; Tuszewska, R.

    1981-01-01

    The results of treatment with radon inhalations of 101 patients with various diseases of the visual system affecting the posterior segment of the eyeball are reported. In most cases clinical improvement was obtained. This was due to a favourable effect of radon on tissue blood flow and its mobilizing action on the reticuloendothelial system. Ophthalmoscopy demonstrated in the treated patients arterial vasodilation in the retina, resorption of haemorrhages and exudates. (author)

  20. Improvement of Brain Tissue Oxygenation by Inhalation of Carbogen

    Ashkanian, M.; Borghammer, P.; Gjedde, A.

    2008-01-01

    tomography (PET) to measure CBF and cerebral metabolic rate of oxygen (CMRO(2)) during inhalation of test gases (O(2), CO(2), carbogen and atmospheric air) in 10 healthy volunteers. Arterial blood gases were recorded during administration of each gas. The data were analyzed with volume-of-interest and voxel...... is sufficient for optimal oxygenation of healthy brain tissue, whereas carbogen induces concomitant increases of CBF and Sa(O2)....

  1. Biological basis of inhalation exposure of radon and its daughters

    Matsuoka, Osamu

    1989-01-01

    Since inhalation exposure by radon and its daughters is very specific type of internal exposure, it is necessary to understand its characteristic nature. The specificity originates from the nuclear feature of radon daughters and the biological micro-environment in the respiratory tract. Inhaled radon and its daughters exist in the respiratory tract as ions attached to air dusts and deposit on the mucus surface of the respiratory tract by various mechanisms such as impaction, sedimentation and diffusion. Deposition of radon daughters is predominant around the site of the fourth generation according to Weibel's model. Deposited particles with radon daughters are cleared by muco-ciliary transportation. Its speed is estimated to be about 1.0 cm/min, at the upper region. Alpha decay will happen during transportation in the respiratory tract. Radon has no tissue affinity metabolically. Therefore, the irradiation is limited to the epithelial cells of respiratory tract. The cell components within 30-70 micron in depth are irradiated with alpha particle. Biological effectiveness of alpha radiation is very high compared with beta or gamma radiation. The target cell for carcinogenesis by radon exposure is considered to be the basal cell of epithelium. Lung cancer induced by radon inhalation is recognized to be squamous cell carcinoma, small cell carcinoma, or oat-cell carcinoma and adenocarcinoma. The modification factors which influence the effect of radon exposure are co-inhalation of ore dust and smoking habit. According to epidemiological studies on lung cancer which occurred in uranium miners, it is suggested that the smoking habit strongly promotes lung cancer induction. (author)

  2. Biological effects of inhaled cigarette smoke in beagle dogs

    Stuart, B.O.; Palmer, R.F.; Filipy, R.E.; Dagle, G.E.

    1978-01-01

    A group of twenty dogs has received up to 7 yr of daily cigarette smoking (10 cigarettes per day, 5 days per week), using realistic methods of oral inhalation and nose-plus-mouth exhalation. Three dogs that received 20 cigarettes per day over 9 mo developed respiratory tract lesions, including pleural thickening, alveolar septal fibrosis, vesicular emphysema, and chronic bronchitis, more rapidly than dogs receiving 10 cigarettes per day

  3. Toxicity of inhaled 91YCl3 in Beagle dogs. XII

    Muggenburg, B.A.; Rebar, A.H.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1978-01-01

    Studies on the metabolism, dosimetry and effects of inhaled 91 YCl 3 in Beagle dogs are being continued to provide information that will aid in assessing the biological consequences of nuclear accidents in which 91 Y or other radionuclides that produce a similar radiation dose pattern may be released. Forty-two dogs with 91 Y initial body burdens from 64 to 1300 μCi/kg body weight was placed in four groups with mean lung burdens of 310, 180, 75 and 40 μCi/kg body weight. These dogs and 12 control dogs are being maintained for lifetime observation. An additional group of four dogs with a mean initial 91 Y body burden of 180 μCi/kg body weight was placed in a sacrifice study. Twenty-six of the exposed dogs and four of the control dogs have died. Eleven dogs within the highest activity level groups died or were euthanized at 12 to 33 days after inhalation of 91 Y with changes related to severe bone marrow damage and associated pancytopenia. Two dogs died approximately one year after 91 Y inhalation with convulsive seizures that were presumed to be unrelated to the 91 Y exposure. Nine 91 Y-exposed dogs died or were euthanized due to neoplasms 2012 to 4115 days after exposure. Three dogs had nasal squamous cell carcinomas, one had a bronchioloalveolar carcinoma, one a mast cell sarcoma, one a mammary adenocarcinoma, one a malignant lymphoma, one a melanosarcoma in the mouth and one heart base tumor. Two dogs died of renal failure 2663 and 4086 days after exposure. One dog died with autoimmune hemolytic anemia 3888 days after exposure and one died with congestive heart failure 4042 days after inhalation exposure. One control dog died of empyema, another control dog died with a mammary adenocarcinoma, one died with congestive heart failure and one with malabsorption syndrome. Serial observations are continuing on all surviving dogs

  4. Study of a plutonium oxide fuel inhalation case

    Foster, P.P.

    1991-01-01

    Lung retention, urine excretion and faecal excretion levels of plutonium fuel have been measured for an employee following a known inhalation. The employee has had no subsequent contact with the fuel material. The retention and excretion patterns are, however, complicated by a long previous history of suspected small exposures. The monitoring data are presented together with an interpretation of the data which can be compared directly with single intake retention and excretion function as given in ICRP 54. (author)

  5. Lung epithelial permeability and inhaled furosemide. Added dimensions in asthmatics

    Bhure, U.N.; Bhure, S.U.; Bhatt, B.M.; Mistry, S.; Pednekar, S.J.; Chari, V.V.; Desai, S.A.; Joshi, J.M.; Paidhungat, A.J.

    2009-01-01

    Lung clearance rates of inhaled 99m Tc-diethylene-triamine-pentaacetic acid (DTPA) aerosols constitute a sensitive index to evaluate the permeability changes characteristic of airway epithelial damage. It was thought that edema of the airway wall which is reported in asthma could be relieved with a diuretic like furosemide, helping to relieve the symptoms. We intended to study the effect of inhaled furosemide on lung epithelial permeability in asthmatics and smokers with the help of 99m Tc-DTPA lung clearance test (LCT). The study included three groups (n=15), viz. normal healthy controls, asymptomatic chronic smokers, and chronic persistent asthmatics. Each subject underwent the LCT twice, baseline and post-furosemide (Lasix) study, within a week's interval. The post-furosemide study was carried out 15 min after inhalation of 10 mg of lasix. Lung epithelial permeability was determined in terms of clearance half-life (T 1/2 ). The baseline mean T 1/2 values for controls, smokers, and asthmatics were 50.95±16.58, 20.81±5.47, 24.06±6.19 min, respectively. Post-lasix T 1/2 values were 50.83±15.84, 20.70±5.65, 41.27±15.07 min, respectively. There was a significant difference (P<0.001) in baseline and post-lasix clearance values in asthmatics only. Baseline lung epithelial permeability was altered in smokers and asthmatics compared to the controls. Furosemide was effective only in asthmatics in reverting the permeability almost back to the normal range. Inhaled furosemide was effective even in moderate and severe asthmatics. Furosemide has multiple mechanisms of action. It possibly acts at bronchial level in view of the pathology in asthmatics lying in the airways. (author)

  6. Inhaled Antibiotics in the Treatment of Nosocomial Pneumonia

    A. N. Kuzovlev; V. V. Moroz; A. M. Golubev; S. G. Polovnikov

    2013-01-01

    Nosocomial pneumonia is the most common nosocomial infection in intensive care units. Rational antibiotic therapy is the basis for the treatment of nosocomial pneumonia. There is currently a challenge of the pathogens of nosocomial pneumonia being resistant to most of the antibiotics recommended for its treatment. Inhaled antibiotics used in combination with systemic drugs are an effective and safe treatment for nosocomial pneumonia. This review of literature characterizes the current possibi...

  7. IRIS Toxicological Review of 1,4-Dioxane (with Inhalation ...

    EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of 1,4-Dioxane (with inhalation update) that when finalized will appear on the Integrated Risk Information System (IRIS) database. 1,4-Dioxane is commonly used as a solvent, cleaning agent, chemical stabilizer, surface coating, adhesive agent, and an ingredient in chemical manufacture.

  8. Inhalation Exposure Input Parameters for the Biosphere Model

    K. Rautenstrauch

    2004-01-01

    This analysis is one of 10 reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. Inhalation Exposure Input Parameters for the Biosphere Model is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling, and the plan for development of the biosphere abstraction products for TSPA, as identified in the Technical Work Plan for Biosphere Modeling and Expert Support (BSC 2004 [DIRS 169573]). This analysis report defines and justifies values of mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of ERMYN to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception

  9. Methaemoglobinaemia due to amyl nitrite inhalation: a case report.

    Machabert, R; Testud, F; Descotes, J

    1994-05-01

    Methaemoglobinaemia is a potential toxic effect of aliphatic nitrites which are increasingly abused by male homosexuals and drug addicts because of marked vasodilating properties ('poppers'). In most instances, severe complications were described following the ingestion of large quantities of amyl, butyl or isobutyl nitrites. A deficiency in NADH-dependent haemoglobin reductase in some patients has been noted. This is the first report of symptomatic methaemoglobinaemia following the inhalation of amyl nitrite.

  10. Dose-effect studies with inhaled plutonium in beagles

    Anon.

    1982-01-01

    Data are presented for all dogs employed in current life-span dose effect studies with inhaled 239 PuO 2 , and 239 Pu nitrate. Information is presented on the estimated initial alveolar deposition, based on external thorax counts and on estimated lung weights at time of exposure. Information is also provided on the current interpretation of the most prominent clinical-pathological features associated with the death of animals

  11. Exposures from external radiation and from inhalation of resuspended material

    Jacob, P.; Roth, P.; Golikov, V.; Balonov, M.; Erkin, V.; Likhtariov, I.; Garger, E.; Kashparov, V.

    1996-01-01

    In the modelling of external exposures due to cesium released during the reactor accident of Chernobyl, gamma dose rates in air over open undisturbed sites are considered to be different according to the unsoluble fraction in the deposit. This is taken into account by forming different classes according to the distance from the Chernobyl NPP. The effect of the different migration behavior in these distance classes on the gamma dose rate in air is found to increase with time. Predictions of gamma dose rates in air are based on measurements of the nuclear weapons tests fallout. Various population groups in the CIS countries are defined according to their place of residence (rural or urban), their occupation or age (indoor resp. outdoor workers, pensioners, school-children, or preschool-children), and their kind of residence (wooden, brick, or multi-storey house). Model results for various population groups are compared with the results of TLD-measurements of individual external exposures. For the calculation of inhalation doses, the new ICRP model for the respiratory tract was used. The dose assessments were conducted for measured size resolved activity distributions of resuspended material, obtained at different locations and for several kinds of agricultural operations. Inhalation doses vary considerably with respect to different kinds of work. Tractor drivers receive much higher doses than other agricultural workers, especially when the cabin window of the tractor is open. Effective doses due to the inhalation of resuspended plutonium are assessed to be a few μSv per initial deposit of one kBq/m 2 . Inhalation doses from 137 Cs are usually smaller by an order of magnitude than the doses from Pu, provided a high solubility is assumed for resuspended Cs

  12. Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line therapy for persistent asthma in steroid-naive adults and children.

    Ni Chroinin, Muireann

    2009-01-01

    Consensus statements recommend the addition of long-acting inhaled ss2-agonists (LABA) only in asthmatic patients who are inadequately controlled on inhaled corticosteroids (ICS). It is not uncommon for some patients to be commenced on ICS and LABA together as initial therapy.

  13. Toxicity studies of inhaled beta-emitting radionuclides - Status report

    Hahn, F F; Boeker, B B; Gillett, N A; Griffith, W C; Lundgren, D L; McClellan, R O; Muggenburg, B A; Snipes, M B

    1988-12-01

    The effects of beta-emitting radionuclides inhaled in either a relatively soluble form ({sup 90}SrCl{sub 2}, {sup 144}CeCl{sub 3}, {sup 91}yl{sub 3}, or {sup 137}CsCl) or in a relatively insoluble form ({sup 90}Y, {sup 91}Y, {sup 144}Ce or {sup 90}Sr in fused aluminosilicate particles [FAP]) have been studied in laboratory animals. The results showed that the total beta dose and the dose-rate pattern can modify both the neoplastic and non-neoplastic effects of inhaled beta-emitting radionuclides. In addition, the solubility and chemical characteristics of the radionuclides influence which organs are affected. Effects are seen primarily in organs where the radionuclide is ultimately accumulated, e.g., lung, bone, liver, or tracheobronchial lymph nodes. In addition, effects may be seen in organs where there is little accumulation, but where the radiation dose may still be high, e.g., nasal epithelium and heart. Studies of inhaled {sup 144}Ce-FAP in four different species showed that, compared to mice and dogs, lung tumor risk factors are very low for Syrian hamsters and high for rats. Studies of mice, Syrian hamsters, rats, and dogs repeatedly exposed to aerosols of {sup 144}Ce-FAP showed that lung tumor incidence correlates better with cumulative dose to the lung than with dose rate. Most of the studies in this program are nearing completion and full analyses are in progress. (author)

  14. Minimizing variability of cascade impaction measurements in inhalers and nebulizers.

    Bonam, Matthew; Christopher, David; Cipolla, David; Donovan, Brent; Goodwin, David; Holmes, Susan; Lyapustina, Svetlana; Mitchell, Jolyon; Nichols, Steve; Pettersson, Gunilla; Quale, Chris; Rao, Nagaraja; Singh, Dilraj; Tougas, Terrence; Van Oort, Mike; Walther, Bernd; Wyka, Bruce

    2008-01-01

    The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD).

  15. Intermittent inhaled corticosteroids in infants with episodic wheezing

    Bisgaard, Hans; Hermansen, Mette Northman; Loland, Lotte

    2006-01-01

    BACKGROUND: We hypothesized that asthma is preceded by a stage of recurrent episodes of wheezing during the first years of life and that inhaled corticosteroid therapy during symptomatic episodes in this early phase may delay progression to persistent wheezing. METHODS: We assigned one-month-old ......BACKGROUND: We hypothesized that asthma is preceded by a stage of recurrent episodes of wheezing during the first years of life and that inhaled corticosteroid therapy during symptomatic episodes in this early phase may delay progression to persistent wheezing. METHODS: We assigned one......-month-old infants to treatment with two-week courses of inhaled budesonide (400 mug per day) or placebo, initiated after a three-day episode of wheezing, in this single-center, randomized, double-blind, prospective study of three years' duration. The primary outcome was the number of symptom-free days; key...... secondary outcomes were the time to discontinuation due to persistent wheezing and safety, as evaluated by height and bone mineral density at the end of the study. RESULTS: We enrolled 411 infants and randomly assigned 294 to receive budesonide at a first episode of wheezing. The proportion of symptom...

  16. Organ dose from inhaled radionuclides taking lull period into account

    Datta, S.

    1982-01-01

    The dosimetry of inhaled radionuclides is generally carried out in accordance with the lung model recommended by the ICRP Task Group on Lung Dynamics. The relevant expressions are integrated over a given period, assuming continuous inhalation in an atmosphere of constant aerosol concentration. Though for the same amount of intake the dose commitment is found to be independent of variations in the rate of intake, the dose determined over specific intervals of time, is influenced by it or by lull intervals therein. Formulae are developed to arrive at doses to different organs when the subject's intake is constant and continuous for 8 hours, followed by a lull period of 16 hours each day. Results are given for a number of radionuclides and are compared with values characteristic of continuous inhalation. It is observed that when exposure is assumed to be continuous the dose for the same intake of activity is underestimated as compared to the dose when lull period is taken into account. For working periods of 6 days and 30 days the underestimate ranges from 5%-20% and 0.6% to 4.5% respectively. (author)

  17. Nanoparticles: a review of particle toxicology following inhalation exposure.

    Bakand, Shahnaz; Hayes, Amanda; Dechsakulthorn, Finance

    2012-01-01

    It is expected that the rapid expansion of nanotechnology will bring many potential benefits. However, initial investigations have demonstrated that nanomaterials may adversely affect human health and the environment. By increasing the application of nanoparticles, protection of the human respiratory system from exposure to airborne nanoparticles and ultrafine particulates has become an emerging health concern. Available research has demonstrated an association between exposure to ambient airborne particulates and ultrafine particles and various adverse heath effects including increased morbidity and mortality. Nanomaterial structures are more likely to be toxic than the same materials of conventional sized samples and can be inhaled more deeply into the lungs. While the respiratory tract is considered as the primary target organ for inhaled nanoparticles, recent research has demonstrated that extrapulmonary organs are also affected. The very small size distribution and large surface area of nanoparticles available to undergo reactions may play a significant role in nanotoxicity, yet very little is known about their interactions with biological systems. This review explores the possible underlying toxicity mechanisms of nanoparticles following inhalational exposure. Nanoparticles differ from the same conventional material at a larger scale in physical, chemical and biological characteristics; therefore it is critical to recognize the potential risk of nanoparticle exposure using appropriate toxicity test methods. Current advances and limitations of toxicity assessment methods of nanoparticles are discussed highlighting the recent improvements of in vitro screening tools for the safety evaluation of the rapidly expanding area of nanotechnology.

  18. Toxicity of inhaled 91YCl3 in beagle dogs. X

    Muggenburg, B.A.; Benjamin, S.A.; Boecker, B.B.; McClellan, R.O.

    1976-01-01

    Studies on the metabolism, dosimetry, and effects of inhaled 91 YCl 3 in Beagle dogs are being continued to provide information that will aid in assessing the biological consequences of nuclear accidents in which 91 Y or other radionuclides that produce a similar radiation dose pattern may be released. Forty-two dogs with 91 Y initial body burdens from 64 to 1300 μCi/kg body weight were placed in four groups with mean lung burdens of 310, 180, 75 and 40 μCi/kg body weight. These dogs and 12 control dogs are being maintained for lifetime observation. An additional group of four dogs with a mean initial 91 Y body burden of 180 μCi/kg body weight were placed in a sacrifice study. Eleven dogs within the highest activity level groups died or were euthanized at 12 to 33 days after inhalation of 91 Y with changes related to severe bone marrow damage and associated pancytopenia. Two dogs died approximately 1 yr after 91 Y inhalation with convulsive seizures that were presumed to be unrelated to the 91 Y exposure. Five 91 Y-exposed dogs died or were euthanized due to neoplasms 2000 to 3341 days after exposure. Three dogs had nasal squamous cell carcinomas, one had a bronchioloalveolar carcinoma and another, a mast cell sarcoma. One dog died of renal failure 2660 days after exposure and one control dog died of empyema. Serial observations are continuing on all surviving dogs

  19. Toxicity of inhaled Ca-DTPA in the beagle dog

    Smith, V.H.; Ragan, H.A.; Lund, J.E.; Hackett, P.L.

    1975-01-01

    There are several advantages to the administration of Ca- DTPA by inhalation rather than intravenous drip for the decorporation of certain radionuclides. Among these are the possibility of treating very promptly following an accidental incorporation to achieve maximum treatment effectiveness and convenince for medical management, even to the extent that treatment can be self-administered. The present investigational New Drug permit allows treatment of humans only by the intravenous route and animal studies are required to justify the new route. Earlier work in rats and hamsters showed five successive daily inhalations of Ca-DTPA aerosols (dose 1 to 4 times human i.v. dose) produced a transitory emphysema in 17/40 rats serially sacrificed up to 3 weeks following the last exposure and in 10/20 hamsters up to 1 week after exposure. No emphysema was seen in rats sacrificed after 3 weeks and in hamsters after 1 week following the exposures. Results of tests in dogs administered DTPA by inhalation showed hyperplasia of the gastric submucosal lymphoid follicles observed 1 week following the last exposure may be treatment-related, but other observed changes were considered unrelated. (U.S.)

  20. Quantity and Quality of Inhaled Dose Predicts Immunopathology in Tuberculosis

    Kevin Patrick Fennelly

    2015-06-01

    Full Text Available Experimental animal models of tuberculosis (TB have convincingly demonstrated that inhaled dose predicts immunopathology and survival. In contrast, the importance of inhaled dose has generally not been appreciated in TB epidemiology, clinical science, or the practice of TB control. Infectiousness of TB patients has traditionally been assessed using microscopy for acid-fast bacilli in the sputum, which should be considered only a risk factor. We have recently demonstrated that cough aerosol cultures from index cases with pulmonary TB are the best predictors of new infection among household contacts. We suggest that cough aerosols of M. tuberculosis are the best surrogates of inhaled dose, and we hypothesize that the quantity of cough aerosols is associated with TB infection versus disease. Although several factors affect the quality of infectious aerosols, we propose that the particle size distribution of cough aerosols is an important predictor of primary upper airway disease and cervical lymphadenitis and of immune responses in exposed hosts. We hypothesize that large droplet aerosols (> 5 microns containing M. tuberculosis deposit in the upper airway and can induce immune responses without establishing infection. We suggest that this may partially explain the large proportion of humans who never develop TB disease in spite of having immunological evidence of M. tuberculosis infection (e.g. positive TST or IGRA. If these hypotheses are proven true, they would alter the current paradigm of latent TB infection and reactivation, further demonstrating the need for better biomarkers or methods of assessing TB infection and the risk of developing disease.

  1. Is the human nasal cavity at risk from inhaled radionuclides?

    Boecker, B.B.; Hahn, F.F.; Cuddihy, R.G.; Snipes, M.B.; McClellan, R.O.

    1986-01-01

    In a series of three life-span studies in which beagle dogs inhaled relatively soluble forms of beta-emitting radionuclides, a number of cancers of the nasal cavity have arisen at long times after the inhalation exposure. No such cancers were observed in the control dogs. Data obtained in other studies involving serial sacrifice of dogs that received these radionuclides in similar forms have shown that high local concentrations of the radionuclides can persist in nasal turbinates for long periods of time, depending on the physical half-life of the radionuclide inhaled. Several nasal carcinomas have also been observed in dogs injected with 137 CsCl in which the relative concentrations of beta activity in the turbinate region were not as pronounced as in the above studies. Similar risks of sinonasal cancer were calculated for dogs in each of these studies regardless of differences in radionuclide, dosimetry, and route of administration. Since sinonasal cancers have occurred in people exposed to alpha-emitting radionuclides, it is reasonable to assume this could occur with beta emitters as well. Radiation protection guidelines should account for the sinonasal region being at risk. 23 refs., 1 fig., 6 tabs

  2. Formulation and evaluation of CFC free inhalers for beclomethasone dipropionate

    Gopala Krishna Murthy Talasila

    2013-06-01

    Full Text Available Beclomethasone dipropionate CFC free inhalation formulations were developed with a view to treat asthma prophylactically. Dry powder inhalers (DPI for beclomethasone dipropionate were prepared with different grades of lactose monohydrate. The influence of carrier and overages on performance of DPI was studied. Metered dose inhalers (MDI with HFA based propellants were formulated with various doses, overages and different concentrations of alcohol. Formulated DPI and MDI were evaluated for various official and unofficial quality control tests. The influence of over doses on valve delivery, effect of overages on emitted dose and influence of alcohol on spray pattern from MDI were studied. The better fine particle fraction and emitted dose were obtained from the DPI formulated with 10:90 ratio of fine lactose: coarse lactose and with 20% w/w overages. The studies on MDI revealed that the 15% of overdoses are required for effective valve delivery and 20% overages are required for 100% drug delivery. 5-10%v/v alcohol was found to be preferable to get optimum emitted dose and fine particle fraction.

  3. Derived ERLs for inhalation of alpha-emitting aerorols

    Macdonald, H.F.

    1977-01-01

    Derived alpha action levels are expressed as dpm/m 3 and give the airborne concentration of an assumed mixture of α-emitters which if inhaled for a period of 4 hours would result in a dose commitment to members of the critical group in the exposed population equal to the emergency reference levels (ERLs) of dose recommended by the Medical Research Council (1975). The period of 4 hours is chosen as a realistic time during which an assessment of the severity of a release may be made and appropriate countermeasures instituted. The derived α ERLs are set with reference to the potential range of isotopic releases for a specific reactor system and in the case of gas-cooled magnox reactors, a value of 10 3 dpm/m 3 (170 Bqm -3 ) has been used. This level was based upon the lung and GI tract models originally recommended by ICRP 2 (1959:1964) and revised ERLs for the inhalation of α-emitters consequent upon the improved metabolic models subsequently proposed by the ICRP (1966:1972) are evaluated. It is shown that the derived α ERLs for irradiated magnox and AGR fuels are largely independent of the physico-chemical forms of the released material, while variations with cooling time of fuel are also discussed. In addition, the special limits imposed by the chemical toxicity of uranium when inhaled in a soluble, low enriched form are briefly outlined

  4. Estimating inhalation hazards for space nuclear power systems

    Hoover, M.D.; Cuddihy, R.G.; Seiler, F.Z.

    1989-01-01

    Minimizing inhalation hazards is a major consideration in the design, development, transportation, handling, testing, storage, launch, use, and ultimate disposition of nuclear space power systems (NSPSs). An accidental dispersion of 238 Pu is of concern for missions involving the radioisotope thermoelectric generators (RTGs) or lightweight radioisotope heater units. Materials of concern for missions involving a nuclear reactor might include other radionuclides, such as uranium, or chemically toxic materials, such as beryllium or lithium. This paper provides an overview of some of the current approaches and uncertainties associated with estimating inhalation hazards from potential NSPS accidents. The question of whether inhalation risks can be acceptable for nuclear space power systems is still open and active. The inherently low toxicity of the uranium fuel of a space nuclear reactor is a desirable feature of that option. The extensive engineering and testing that have contributed to the current generation of plutonium RTGs provide a measure of confidence that dispersion of the RTG fuel would be unlikely in an accident. The use of nuclear reactors or RTGs in space, however, requires society to assume a risk (albeit low) for dispersion of the fuel material. It can be argued that any additional risks from the use of nuclear power in space are far less than the risks we face daily

  5. Toxicity of inhaled 91YCl3 in beagle dogs. VII

    Muggenburg, B.A.; Benjamin, S.A.; Boecker, B.B.; McClellan, R.O.

    1974-01-01

    Studies on the metabolism, dosimetry, and effects of inhaled 91 YCl 3 in Beagle dogs are being continued to provide information that will aid in assessing the biological consequences of nuclear accidents in which 91 Y or other radionuclides that produce a similar radiation dose pattern may be released. Forty-two dogs with 91 Y initial body burdens from 64 to 1300 μCi/kg body weight were placed in four groups with mean lung burdens of 310, 180, 75, and 40 μCi/kg body weight. These dogs and 12 control dogs are being maintained for lifetime observation. An additional group of four dogs with a mean initial 91 Y body burden of 180 μCi/kg body weight were placed in a sacrifice study. Eleven dogs within the highest activity level groups died or were euthanized at 12 to 33 days after inhalation of 91 Y with changes related to severe bone marrow damage and associated paycytopenia. Two dogs died approximately one year after 91 Y inhalation with convulsive seizures that were presumed to be unrelated to the 91 Y exposure. Four 91 Y-exposed dogs died or were euthanized due to neoplasms 2000 to 2560 days after exposure. Two dogs had squamous cell carcinomas involving the maxillary and nasal regions, one a bronchiolo-alveolar carcinoma of the lung and another, a mast cell sarcoma. One control dog died of empyema. Serial observations are continuing on all surviving dogs. (U.S.)

  6. Aerosol lung inhalation scintigraphy in children with bronchial asthma

    Torii, Yoshikuni; Nakayama, Chikashi; Nakata, Hajime; Takahashi, Satomi; Tanaka, Masaaki; Koori, Tateo

    1988-01-01

    Aerosol lung inhalation scintigraphies performed on 37 children with bronchial asthma during asymptomatic periods were evaluated. The findings of their aerosol lung inhalation scintigrams were classified into 4 patterns, as type I: homogeneous distribution without hot spot formation, type II: peripheral homogeneity with central hot spot formation, type IIID (-): inhomogeneous distribution with hot spot formation, but without defect, and type IIID (+): with defect. These aerosol patterns were compared with those of previously reported adult cases and with the severity of bronchial asthma. Normal pattern of type I was found in 5 cases (12%) of our infantile asthmatics in contrast to previously reported adult cases, in which none of normal pattern was found. There were differences between type II and type III in both distribution and disappearance time of hot spot, which indicated that the two types differed from each other in radioaerosol deposition mechanism. There was no significant correlation between type I and type II in the severity of asthma and the frequency of asthmatic attack. Type II may be clinically considered to be the same type as type I. There is the statistically significant difference between type I, II and type III in the frequency of asthmatic attack, but not in the severity of asthma, although most of serious cases showed type III. Aerosol lung inhalation scintigraphy is a useful examination for children with bronchial asthma in which lung function tests may be difficult to perform. (author)

  7. Treatment outcomes of using inhalation sedation for comprehensive dental care.

    Madouh, M; BaniHani, A; Tahmassebi, J F

    2018-02-01

    To assess the outcomes of dental treatment under inhalation sedation within a UK specialist hospital setting. This was a retrospective cohort study of the case notes of patients under 17 years of age who received dental treatment using inhalation sedation at a UK specialist setting during the period 2006-2011. Treatment outcomes were categorised into five groups: (1) treatment completed as planned, (2) modified treatment completed, (3) treatment abandoned in sedation unit and patient referred for treatment under general analgesia (GA), (4) treatment abandoned in sedation unit and patient referred for treatment under local analgesia (LA), (5) child failed to return to complete treatment. In total, the case notes of 453 patients were evaluated. The mean age of the patients was 10.3 ± 2.9 years. Treatment was completed successfully in 63.6% of the cases, 15.9% were referred for treatment under GA, 11.2% failed to return to complete the treatment, 7.1% received modified treatment completed, and only 2.2% were referred for treatment under LA. Treatment outcomes were significantly associated with patient`s age (p = 0.002). The treatment outcome "treatment abandoned and child referred to be treated under GA" had significantly lower mean patient ages than the other outcomes. The majority of children referred for inhalation sedation, completed their course of treatment. A significantly higher proportion of those in the younger age group required GA to complete their treatment.

  8. Inhalation Exposure Input Parameters for the Biosphere Model

    M. Wasiolek

    2006-06-05

    This analysis is one of the technical reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), referred to in this report as the biosphere model. ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. ''Inhalation Exposure Input Parameters for the Biosphere Model'' is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the biosphere model is presented in Figure 1-1 (based on BSC 2006 [DIRS 176938]). This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and how this analysis report contributes to biosphere modeling. This analysis report defines and justifies values of atmospheric mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of the biosphere model to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception. This

  9. Inhalation Exposure Input Parameters for the Biosphere Model

    M. Wasiolek

    2006-01-01

    This analysis is one of the technical reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN), referred to in this report as the biosphere model. ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. ''Inhalation Exposure Input Parameters for the Biosphere Model'' is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the biosphere model is presented in Figure 1-1 (based on BSC 2006 [DIRS 176938]). This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling and how this analysis report contributes to biosphere modeling. This analysis report defines and justifies values of atmospheric mass loading for the biosphere model. Mass loading is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Mass loading values are used in the air submodel of the biosphere model to calculate concentrations of radionuclides in air inhaled by a receptor and concentrations in air surrounding crops. Concentrations in air to which the receptor is exposed are then used in the inhalation submodel to calculate the dose contribution to the receptor from inhalation of contaminated airborne particles. Concentrations in air surrounding plants are used in the plant submodel to calculate the concentrations of radionuclides in foodstuffs contributed from uptake by foliar interception. This report is concerned primarily with the

  10. Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations.

    McKeever, Tricia; Mortimer, Kevin; Wilson, Andrew; Walker, Samantha; Brightling, Christopher; Skeggs, Andrew; Pavord, Ian; Price, David; Duley, Lelia; Thomas, Mike; Bradshaw, Lucy; Higgins, Bernard; Haydock, Rebecca; Mitchell, Eleanor; Devereux, Graham; Harrison, Timothy

    2018-03-08

    Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma. We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma. A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group. In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology

  11. Puffing and inhalation behaviour in cigarette smoking: Implications for particle diameter and dose

    Dickens, Colin; McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John, E-mail: colin_dickens@bat.co [British American Tobacco, Group R and D Centre, Southampton, SO15 8TL (United Kingdom)

    2009-02-01

    Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of diameter 150 - 250 nm CMD. Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, it was noted that particle deposition increased with increasing inhalation depth, and that smoke inhalation volumes were generally greater than normal tidal breathing volumes. A weak association was observed between particle diameter and puff flow, but no strong association between particle diameter and retention efficiency.

  12. Puffing and inhalation behaviour in cigarette smoking: Implications for particle diameter and dose

    Dickens, Colin; McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John

    2009-01-01

    Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of diameter 150 - 250 nm CMD. Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, it was noted that particle deposition increased with increasing inhalation depth, and that smoke inhalation volumes were generally greater than normal tidal breathing volumes. A weak association was observed between particle diameter and puff flow, but no strong association between particle diameter and retention efficiency.

  13. Difference in pulmonary absorption of inhaled terbutaline in healthy smokers and non-smokers.

    Schmekel, B; Borgström, L; Wollmer, P

    1991-01-01

    Pathophysiological studies have shown that the alveolocapillary transfer of small solutes is much faster in healthy smokers than in non-smokers. The effects of smoking on the pulmonary absorption of inhaled terbutaline were examined in normal subjects. Nine healthy smokers and 13 healthy non-smokers inhaled nebulised terbutaline and dry terbutaline powder on two study days. Plasma concentrations of terbutaline were measured up to 240 minutes after the inhalation. The plasma concentration of t...

  14. Identification of inhaler technique errors with a routine procedure in Portuguese community pharmacy

    Castel-Branco MM

    2017-12-01

    Full Text Available Background: A correct selection of drugs prescribed, but also the choice of the appropriate inhaler device, is crucial for the control of respiratory diseases. Objective: To evaluate the inhaler technique and identify potential errors of patients when treated with inhalers by testing a routinary procedure to be implemented in any community pharmacy. Methods: Adults with asthma/COPD and under inhalation therapy were invited to demonstrate how they use their inhalers. After direct observation it was registered whether all the sequential steps included in the summary of product characteristics (SmPC were performed. Results: The study involved 67 patients from 4 community pharmacies (Portugal central region: 34 (50.7% males, 65.4 (SD=18.28 years old, 42 (62.7% with COPD, and 23 (34.3% using more than one inhaler. The 67 patients used 95 inhalers, comprising: 57 (60.0% multiple dose DPI (dry powder inhalers, 18 (18.9% single dose DPI, 16 (16.8% pMDI (pressurized metered dose inhalers, 2 (2.1% pMDI+spacer and 2 (2.1% SMI (soft mist inhalers. No errors were made only by 9 (13.4% patients. In the 75 DPIs techniques, the most frequent errors were ‘no previous forced expiration’ (46=61.3% and ‘no 10s apnea after inhalation’ (51=68.0%; in the 16 pMDIs techniques common errors were ‘lack of hand-lung coordination’ (7=43.8 %, ‘no previous forced exhalation’ (8=50.0% and ‘no apnea after inhalation’ (10=62.5%. After inhaling from 56 devices containing corticosteroids, 34 (60.7% of the patients did not wash their mouth. Conclusion: The study demonstrated the possibility of performing this procedure routinely in Portuguese community pharmacies and also its utility, since 58 (87% of patients had at least one error during the inhalers use.

  15. Practice makes perfect: self-reported adherence a positive marker of inhaler technique maintenance

    Azzi, Elizabeth; Srour, Pamela; Armour, Carol; Rand, Cynthia; Bosnic-Anticevich, Sinthia

    2017-01-01

    Poor inhaler technique and non-adherence to treatment are major problems in the management of asthma. Patients can be taught how to achieve good inhaler technique, however maintenance remains problematic, with 50% of patients unable to demonstrate correct technique. The aim of this study was to determine the clinical, patient-related and/or device-related factors that predict inhaler technique maintenance. Data from a quality-controlled longitudinal community care dataset was utilized. 238 pa...

  16. Opinion of pneumologists on the importance of inhalers in patients with asthma or COPD

    Mitja Košnik

    2017-04-01

    Full Text Available Background: Medications for asthma and COPD are mainly used in the form of inhalations. A survey was performed to obtain the opinion of experts about the importance of inhalers in inhaled drug therapy.Methods: All members–pulmonologists of the Slovenian Respiratory Society were invited to participate in the survey using a two-stage Delphi method. The result of each response were shown by the median and interquartile range, whereby we calculated the level of consensus.Results: 176 doctors were invited. Most questions were answered by 49 (27.8 % participants. In the second round 42 doctors responded. As many as 33 out of 41 respondents (80.5 % felt that in the treatment of asthma and COPD the selection of medicines and inhalers are equally important. When choosing an inhaler, it is crucial that it is simple to instruct the patients about its use. Respondents highly agreed with the statement that patients should receive a prescription for inhaler only after they have been trained on how to use it. As appropriate persons for the training of patients on the use of inhalers the respondents recognized (from most to least suitable pulmonologists, nurses, general practitioners or pharmacists. 53.8 % of respondents considered that the patient’s skill of the use of inhaler should be checked on every visit to the doctor. Respondents believed that replacing inhalers without consulting the treating doctor may result in incorrect use of the inhaler, poor patient compliance, more exacerbations of the disease and poorer disease control. Some consensus with an indifferent median of 4.5 was reached with regard to the argument that the doctor should prescribe the inhaler that is the cheapest for society.Conclusions: Slovenian pulmonologists believe that any change of inhaler is a critical event, which must be coordinated with the patient and the doctor.

  17. Activities of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro.

    Patick, A K; Boritzki, T J; Bloom, L A

    1997-10-01

    Nelfinavir mesylate (formerly AG1343) is a potent and selective, nonpeptidic inhibitor of human immunodeficiency virus type 1 (HIV-1) protease that was discovered by protein structure-based design methodologies. We evaluated the antiviral and cytotoxic effects of two-drug combinations of nelfinavir with the clinically approved antiretroviral therapeutics zidovudine (ZDV), lamivudine (3TC), dideoxycytidine (ddC; zalcitabine), stavudine (d4T), didanosine (ddI), indinavir, saquinavir, and ritonavir and a three-drug combination of nelfinavir with ZDV and 3TC against an acute HIV-1 strain RF infection of CEM-SS cells in vitro. Quantitative assessment of drug interaction was evaluated by a universal response surface approach (W. R. Greco, G. Bravo, and J. C. Parsons, Pharm. Rev. 47:331-385, 1995) and by the method of M. N. Prichard and C. Shipman (Antiviral Res. 14:181-206, 1990). Both analytical methods yielded similar results and showed that the two-drug combinations of nelfinavir with the reverse transcriptase inhibitors ZDV, 3TC, ddI, d4T, and ddC and the three-drug combination with ZDV and 3TC resulted in additive to statistically significant synergistic interactions. In a similar manner, the combination of nelfinavir with the three protease inhibitors resulted in additive (ritonavir and saquinavir) to slightly antagonistic (indinavir) interactions. In all combinations, minimal cellular cytotoxicity was observed with any drug alone and in combination. These results suggest that administration of combinations of the appropriate doses of nelfinavir with other currently approved antiretroviral therapeutic agents in vivo may result in enhanced antiviral activity with no associated increase in cellular cytotoxicity.

  18. Opportunities for inhaler device selection in elderly patients with asthma or COPD

    Barrons R

    2015-12-01

    Full Text Available Robert Barrons,1 James Wheeler,2 J Andrew Woods1 1Wingate University School of Pharmacy, Wingate, NC, USA; 2University of Tennessee Health Science Center, Nashville, TN, USA Abstract: An anticipated surge in the elderly population will be accompanied by a rise in aging patients with asthma or COPD. Clinician selection of inhalers needs to address the unique challenges to elderly patients. These challenges to the use of inhalers include diminished physical and cognitive abilities, as well as cost reimbursement issues associated with polypharmacy and the Medicare gap. Clinicians should consider patient preferences for an inhaler device that provides ease of administration, and addresses conveniences such as portability, visual, and auditory indicators of dosing completion. The addition of spacer devices resolves hand-breath coordination difficulty with pressurized metered dose inhalers, but reduces overall inhaler convenience. Soft mist inhalers (Respimat® improve ease of administration, but use may be limited by cost and formulary availability. Multiple dose dry powder inhalers provide convenience and simplified use by requiring only one to two steps prior to administration, but concerns of peak inspiratory flow requirements remain among patients with advanced age and severity of COPD. If unaddressed, these challenges to inhaler selection contribute to inappropriate use of inhalers in 41% to 69% of patients, accompanied by at least 51% non-adherence to treatment. Clinicians must first avail themselves of reputable educational resources regarding new inhaler developments and administration, for competent patient instruction. Patient education should include a checklist of inhaler technique, with physical demonstration of each device by the patient and provider. Device demonstration significantly improves inhaler technique and identifies the need for nebulization therapy. Clinician and patient knowledge of available inhalers and their

  19. Experiment of aerosol-release time for a novel automatic metered dose inhaler

    Mingrong Zhang

    2016-05-01

    Full Text Available The objective of this study was to evaluate the aerosol-release time in the development of a new automatic adapter for metered dose inhaler. With this device, regular manually operated metered dose inhalers become automatic. During the study, an inhalation simulator was designed and tested with the newly developed mechatronic system. By adjusting the volume and the pressure of the vacuum tank, most human inhalation waveforms were able to simulate. As an example, regular quick-deep and slow-deep waveforms were matched within reasonable accuracy. Finally, with the help of dynamic image processing, the aerosol-release time (Tr was carefully measured and fully discussed, including the switch-on time (Ts, the mechatronics-hysteresis (Tm and the intentional-delay (Ti. Under slow-deep inhalation condition which is suitable for metered dose inhaler medicine delivery, the switch-on flow-rate could reach as low as 10 L/min, and the corresponding switch-on time was approximately 0.20 s. While the mechatronics-hysteresis depended on the brand of metered dose inhaler, assuming there was no intentional-delay, the aerosol-release time could be as low as 0.40 and 0.60 s, respectively, for two commercially available metered dose inhalers studied in this article. Therefore, this newly developed mechatronic adapter system could ensure aerosol-release time (Tr within satisfactory range for metered dose inhalers.

  20. Inhalation Toxicology Research Institute. Annual report, October 1, 1981-September 30, 1982

    Snipes, M.B.; Marshall, T.C.; Martinez, B.S.

    1982-12-01

    Studies are presented of the effect on man of airborne particulates and gaseous emissions associated with the production of energy. Included in the report from the Inhalation Toxicology Research Institute are papers on: (1) the physical and chemical characterization of energy technology aerosols; (2) laboratory studies of aerosol generation and characterization; (3) in vitro predictors of toxicity; (4) disposition and fate of inhaled materials; (5) dose-response relationships for inhaled radionuclides; (6) dose-response relationships for inhaled chemical toxicants; (7) biological factors which influence dose-response relationships; and (8) risk assessment

  1. Self-reported osteoporosis prevention in inhaled corticosteroid users in community pharmacy setting

    Valerie Chan

    2015-05-01

    Full Text Available Objectives: The use of inhaled corticosteroids is the standard maintenance therapy in asthma therapy and as adjunct therapy in moderate to severe chronic obstructive pulmonary disease. A dose-related increase in fracture risk is associated with inhaled corticosteroid use; there is an inverse relationship between bone mineral density and duration and cumulative dose of inhaled corticosteroid. Adequate intake of calcium and vitamin D are cornerstones of osteoporosis prevention. The objectives are to assess whether the proportion of patients receiving inhaled corticosteroids are taking calcium and vitamin D; the association between long-term inhaled corticosteroid use and abnormal bone mineral density or fractures; and how many qualified patients received bone mineral density scans. Methods: Patients who filled a prescription for inhaled corticosteroids at selected community pharmacies across Alberta were recruited for a survey of their osteoporosis prevention activities. Results: A total of 256 patients from 12 community pharmacies were included. The average age was 60 ± 17.4 years with 65% female. There were 21%, 51%, and 28% of patients on high, medium, and low dose inhaled corticosteroids, respectively. Only 17% of patients >50 years old received recommended calcium and vitamin D supplementation and 87 (73% of the qualified patients received bone mineral density scan. Conclusion: Osteoporosis prevention in inhaled corticosteroid users is currently poorly addressed. More promotion is needed to raise pharmacist awareness of the risks of inhaled corticosteroids.

  2. Factors related to the incorrect use of inhalers by asthma patients

    Paulo de Tarso Roth Dalcin

    2014-01-01

    Full Text Available OBJECTIVE: To evaluate inhaler technique in outpatients with asthma and to determine associations between the correctness of that technique and the level of asthma control. METHODS: This was a cross-sectional study involving patients > 14 years of age with physician-diagnosed asthma. The patients were recruited from the Asthma Outpatient Clinic of the Hospital de Clínicas de Porto Alegre, in the city of Porto Alegre, Brazil. The patients completed two questionnaires (a general questionnaire and an asthma control questionnaire based on the 2011 Global Initiative for Asthma guidelines, demonstrated their inhaler technique, and performed pulmonary function tests. Incorrect inhaler technique was defined as the incorrect execution of at least two of the predefined steps. RESULTS: We included 268 patients. Of those, 81 (30.2% showed incorrect inhaler technique, which was associated with poor asthma control (p = 0.002. Logistic regression analysis identified the following factors associated with incorrect inhaler technique: being widowed (OR = 5.01; 95% CI, 1.74-14.41; p = 0.003; using metered dose inhalers (OR = 1.58; 95% CI, 1.35-1.85; p 2 comorbidities (OR = 3.80; 95% CI, 1.03-14.02; p = 0.045. CONCLUSIONS: In the sample studied, incorrect inhaler technique was associated with poor asthma control. Widowhood, use of metered dose inhalers, low socioeconomic level, and the presence of > 2 comorbidities were associated with incorrect inhaler technique.

  3. Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

    Westerik, Janine A. M.; Carter, Victoria; Chrystyn, Henry; Burden, Anne; Thompson, Samantha L.; Ryan, Dermot; Gruffydd-Jones, Kevin; Haughney, John; Roche, Nicolas; Lavorini, Federico; Papi, Alberto; Infantino, Antonio; Roman-Rodriguez, Miguel; Bosnic-Anticevich, Sinthia; Lisspers, Karin; Ställberg, Björn; Henrichsen, Svein Høegh; van der Molen, Thys; Hutton, Catherine; Price, David B.

    2016-01-01

    Abstract Objective: Correct inhaler technique is central to effective delivery of asthma therapy. The study aim was to identify factors associated with serious inhaler technique errors and their prevalence among primary care patients with asthma using the Diskus dry powder inhaler (DPI). Methods: This was a historical, multinational, cross-sectional study (2011–2013) using the iHARP database, an international initiative that includes patient- and healthcare provider-reported questionnaires from eight countries. Patients with asthma were observed for serious inhaler errors by trained healthcare providers as predefined by the iHARP steering committee. Multivariable logistic regression, stepwise reduced, was used to identify clinical characteristics and asthma-related outcomes associated with ≥1 serious errors. Results: Of 3681 patients with asthma, 623 (17%) were using a Diskus (mean [SD] age, 51 [14]; 61% women). A total of 341 (55%) patients made ≥1 serious errors. The most common errors were the failure to exhale before inhalation, insufficient breath-hold at the end of inhalation, and inhalation that was not forceful from the start. Factors significantly associated with ≥1 serious errors included asthma-related hospitalization the previous year (odds ratio [OR] 2.07; 95% confidence interval [CI], 1.26–3.40); obesity (OR 1.75; 1.17–2.63); poor asthma control the previous 4 weeks (OR 1.57; 1.04–2.36); female sex (OR 1.51; 1.08–2.10); and no inhaler technique review during the previous year (OR 1.45; 1.04–2.02). Conclusions: Patients with evidence of poor asthma control should be targeted for a review of their inhaler technique even when using a device thought to have a low error rate. PMID:26810934

  4. Inhalable Ipratropium Bromide Particle Engineering with Multicriteria Optimization.

    Vinjamuri, Bhavani Prasad; Haware, Rahul V; Stagner, William C

    2017-08-01

    Spray-dried ipratropium bromide (IPB) microspheres for oral inhalation were engineered using Quality by Design. The interrogation of material properties, process parameters, and critical product quality attributes interplay enabled rational product design. A 2 7-3 screening design exhibited the Maillard reaction between L-leucine (LL) and lactose at studied outlet temperatures (OT) >130°C. A response surface custom design was used in conjunction with multicriteria optimization to determine the operating design space to achieve inhalable microparticles. Statistically significant predictive models were developed for volume median diameter (p = 0.0001, adjusted R 2   = 0.9938), span (p = 0.0278, adjusted R 2   = 0.7912), yield (p = 0.0020, adjusted R 2   = 0.9320), and OT (p = 0.0082, adjusted R 2   = 0.8768). An independent verification batch confirmed the model's predictive capability. The prediction and actual values were in good agreement. Particle size and span were 3.32 ± 0.09 μm and 1.71 ± 0.18, which were 4.7 and 5.3% higher than the predicted values. The process yield was 50.3%, compared to the predicted value of 65.3%. The OT was 100°C versus the predicted value of 105°C. The label strength of IPB microparticles was 99.0 to 105.9% w/w suggesting that enrichment occurred during the spray-drying process. The present study can be utilized to initiate the design of the first commercial IPB dry powder inhaler.

  5. Physicochemical characteristics of chlorofluorohydrocarbon-based inhalation aerosols

    Ashurst, I C

    1985-01-01

    The aim of this work was to gain a better understanding of the physicochemical factors which affect the formulation of suspension inhalation aerosols. The adsorption of six nonionic and cationic surfactants onto Spherisorb has been investigated. The results were analyzed by calculating the area occupied by one adsorbed molecule at the surface and by comparing these values for each surfactant. The amount of each surfactant adsorbed was correlated with the number of sites on that surfactant molecule which could interact with the surface. The stability of suspensions, produced by both the model colloid Spherisorb, and by the drug isoprenaline sulfate, after adsorption of the surfactants, has been assessed by measuring settling times and rising times. The most stable suspension were found to be those which had the greatest amounts of long chain fatty acid surfactant adsorbed on their surface. A comparison was made between the effective stabilizing properties of Span 85 and oleic acid on various drug suspension. It was found that Span 85 gave the most stable suspension. Inhalation aerosol suspensions of isoprenaline sulfate were manufactured using the same surfactants used in the adsorption and suspension stability studies and were analyzed by measuring the particle size distributions of the suspension and the emitted doses. The results were found to correlate with the adsorption and suspension stability studies and it was concluded that a deflocculated suspension was preferable to a flocculated suspension in inhalation aerosols provided that the drug density was less than the propellant density. The application of this work to preformulation studies was also discussed.

  6. Inhalation exposure of children to fragrances present in scented toys.

    Masuck, I; Hutzler, C; Jann, O; Luch, A

    2011-12-01

    When utilized in the perfuming of children's toys, fragrances capable of inducing contact allergy in human skin may also become bioavailable to children via the inhalation route. The aim of this study was to determine the area-specific emission rates of 24 fragrances from a plasticized PVC reference material that was meant to mimic a real plastic toy. This material was introduced into an emission chamber for 28 days at handling conditions or at worst-case conditions. As a result, fragrances can be separated into three categories according to their emission rates ranging from 0.0041 to 16.2 mg/m² × h, i.e., highly volatile, semivolatile, and low-volatile compounds. Compounds of the first and second categories were monitored with decreasing emission rates. Substances of the third category were detected with increasing emission rates over time. Further, higher temperatures led to higher emission rates. The emission concentration of fragrances from four real scented toys varied between 1.10 and 107 μg/m³ at day 1 in the test chamber. Therefore, short-term inhalation exposure to fragrances originating from toys was in the range of 0.53-2700 ng/kg BW/d for the children of age 1 and older. Long-term exposure to these fragrances was calculated in the range of 2.2-220 ng/kg BW/d. Besides household products and cosmetics, fragrances can be found in toys for children. Some fragrances are known contact allergens in the skin, but there is a lack of information on their effects in the human respiratory tract. Here, we analyzed and categorized fragrances present in a plasticized PVC reference material according to their emission profiles and volatility. We also demonstrate that volatile fragrances are being emitted from real toys and thus may get inhaled under consumer conditions to different extents. © 2011 John Wiley & Sons A/S.

  7. Cardiovascular morbidity and the use of inhaled bronchodilators

    Christine Macie

    2008-03-01

    Full Text Available Christine Macie, Kate Wooldrage, Jure Manfreda, Nicholas AnthonisenDepartment of Medicine, University of Manitoba, Winnipeg, Manitoba, CanadaAbstract: We used the Manitoba Health database to examine the relationship between use of inhaled respiratory drugs in people with chronic obstructive respiratory diseases and cardiovascular hospitalizations from 1996 through 2000. The drugs examined were beta agonists [BA], ipratropium bromide IB, and inhaled steroids (ICS. End points were first hospitalizations for supraventricular tachycardia, myocardial infarction, heart failure or stroke. A nested case control analysis was employed comparing people with and without cardiovascular events. Cases and controls were matched for gender and age, and conditional logistic regression was used in multivariate analysis considering other respiratory drugs, respiratory diagnosis and visit frequency, non-respiratory, non-cardiac comorbidities, and receipt of drugs for cardiovascular disease. In univariate analyses, BA, IB and ICS were all associated with hospitalizations for cardiovascular disease, but in multivariate analyses ICS did not increase risk while both BA and IB did. There were interactions between respiratory and cardiac drugs receipt in that bronchodilator associated risks were higher in people not taking cardiac drugs; this was especially true for stroke. There were strong interactions with specific cardiac drugs; for example, both BA and IB substantially increased the risk of supraventricular tachycardia in patients not anti-arryhthmic agents, but not in the presence of such agents. We conclude that bronchodilator therapy for chronic obstructive diseases is associated with increased cardiovascular risk, especially in patients without previous cardiovascular diagnoses, and that this is unlikely due to the severity of the respiratory disease, since risk was not increased with ICS.Keywords: bronchodilator therapy, inhaled corticosteroids, nested case

  8. Toxicity of inhaled 91YCl3 in beagle dogs. XI

    Muggenburg, B.A.; Rebar, A.H.; Benjamin, S.A.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1977-01-01

    Studies on the metabolism, dosimetry and effects of inhaled 91 YCl 3 in Beagle dogs are being continued to provide information that will aid in assessing the biological consequences of nuclear accidents in which 91 Y or other radionuclides that produce a similar radiation dose pattern may be released. Forty-two dogs with 91 Y initial body burdens from 64 to 1300 μCi/kg body weight were placed in four groups with mean lung burdens of 310, 180, 75 and 40 μCi/kg body weight. These dogs and 12 control dogs are being maintained for lifetime observation. An additional group of four dogs with a mean initial 91 Y body burden of 180 μCi/kg body weight were placed in a sacrifice study. Twenty-one of the exposed dogs have died and two of the control dogs have died. Eleven dogs within the highest activity level groups died or were euthanized at 12 to 33 days after inhalation of 91 Y with changes related to severe bone marrow damage and associated pancytopenia. Two dogs died approximately one year after 91 Y inhalation with convulsive seizures that were presumed to be unrelated to the 91 Y exposure. Seven 91 Y-exposed dogs died or were euthanized due to neoplasms 2000 to 3341 days after exposure. Three dogs had nasal squamous cell carcinomas, one had a bronchioloalveolar carcinoma, one, a mast cell sarcoma, one a mammary adenocarcinoma and one with a malignant lymphoma. One dog died of renal failure 2660 days after exposure, one control dog died of empyema and another control dog died with a mammary adenocarcinoma. Serial observations are continuing on all surviving dogs

  9. Modeling Inhalational Tularemia: Deliberate Release and Public Health Response

    Hall, Ian M.; Leach, Steve

    2011-01-01

    Two epidemic modeling studies of inhalational tularemia were identified in the published literature, both demonstrating the high number of potential casualties that could result from a deliberate aerosolized release of the causative agent in an urban setting. However, neither study analyzed the natural history of inhalational tularemia nor modeled the relative merits of different mitigation strategies. We first analyzed publicly available human/primate experimental data and reports of naturally acquired inhalational tularemia cases to better understand the epidemiology of the disease. We then simulated an aerosolized release of the causative agent, using airborne dispersion modeling to demonstrate the potential number of casualties and the extent of their spatial distribution. Finally, we developed a public health intervention model that compares 2 mitigation strategies: targeting antibiotics at symptomatic individuals with or without mass distribution of antibiotics to potentially infected individuals. An antibiotic stockpile that is sufficient to capture all areas where symptomatic individuals were infected is likely to save more lives than treating symptomatic individuals alone, providing antibiotics can be distributed rapidly and their uptake is high. However, with smaller stockpiles, a strategy of treating symptomatic individuals alone is likely to save many more lives than additional mass distribution of antibiotics to potentially infected individuals. The spatial distribution of symptomatic individuals is unlikely to coincide exactly with the path of the dispersion cloud if such individuals are infected near their work locations but then seek treatment close to their homes. The optimal mitigation strategy will depend critically on the size of the release relative to the stockpile level and the effectiveness of treatment relative to the speed at which antibiotics can be distributed. PMID:22044315

  10. Lung Deposition And Biological Effects Of Inhaled Radon Progenies

    Balashazy, I.; Farkas, A.; Szoke, I.; Moustafa, M.; Kudela, G.

    2010-01-01

    Inhaled radon progenies provide more than the half of natural radiation exposure. There is increasing evidence that the cellular distribution of radiation burden is an important factor regarding the biological response to ionisation radiation, thus, one of our tasks was the characterisation of the distribution of cellular exposure. Histological studies of former uranium miners presented strong correlation between primer deposition hot spots and neoplastic lesions. Most of these lesions were located along the carinal regions of the large bronchial airways. In the present work, computational fluid dynamics (CFD) approaches have been applied to simulate the deposition distribution of inhaled radon progenies along central human airways. The geometry and the cellular structure of epithelial lung tissue were numerically reconstructed based on anatomical and histological data. Single and multiple ha-hit and cellular dose distributions have been computed applying Monte Carlo modelling techniques at different breathing conditions. Figure 1. Deposition enhancement factor (EF) of inhaled radon progenies on a central airway bifurcation in airway generations 4-5 during light physical activity breathing condition. Size of scanning surface element is a 45μm side triangle. Left panel: EF max=1400,Dp=200 nm (attached). Right panel: EF max1290, Dp= 1 nm (unattached). Values of local per average deposition densities, that is, enhancement factors (Figure 1), hit probabilities and doses may be up to two-three orders of magnitude higher in the deposition hot spots than the average values. Dose calculations revealed that some cell clusters may receive high doses even at low exposure conditions. Applying the model to different radiation exposure conditions useful relations can be received regarding the linear-non threshold hypothesis

  11. Analysis of uncertainties in CRAC2 calculations: the inhalation pathway

    Killough, G.G.; Dunning, D.E. Jr.

    1984-01-01

    CRAC2 is a computer code for estimating the health effects and economic costs that might result from a release of radioactivity from a nuclear reactor to the environment. This paper describes tests of sensitivity of the predicted health effects to uncertainties in parameters associated with inhalation of the released radionuclides. These parameters are the particle size of the carrier aerosol and, for each element in the release, the clearance parameters for the lung model on which the code's dose conversion factors for inhalation are based. CRAC2 uses hourly meteorological data and a straight-line Gaussian plume model to predict the transport of airborne radioactivity; it includes models for plume depletion and population evacuation, and data for the distributions of population and land use. The code can compute results for single weather sequences, or it can perform random sampling of weather sequences from the meteorological data file and compute results for each weather sequence in the sample. For the work described in this paper, we concentrated on three fixed weather sequences that represent a range of conditions. For each fixed weather sequence, we applied random sampling to joint distributions of the inhalation parameters in order to estimate the sensitivity of the predicted health effects. All sampling runs produced coefficients of variation that were less than 50%, but some differences of means between weather sequences were substantial, as were some differences between means and the corresponding CRAC2 results without random sampling. Early injuries showed differences of as much as 1 to 2 orders of magnitude, while the differences in early fatalities were less than a factor of 2. Latent cancer fatalities varied by less than 10%. 19 references, 6 figures, 3 tables

  12. Pulmonary lesions induced by inhaled plutonium in beagles

    Dagle, G.E.; Lund, J.E.; Park, J.F.

    1976-01-01

    The histopathologic features of pulmonary fibrosis and bronchiolo-alveolar carcinoma in beagles exposed to aerosols of 238 Pu or 239 Pu oxide are reviewed. A hypothesis of the pathogenesis of radiation pneumonitis induced by inhalation of plutonium oxide is presented; this hypothesis included phagocytosis of Pu particles, fibrosis responding to the necrosis, and alveolar cell hyperplasia compensating for alveolar cells killed by alpha radiation. Histopathologic features of the epithelial changes suggest a progression from hyperplasia to metaplasia and, finally, to bronchiolo-alveolar carcinoma. The possibility of concurrent radiation-induced lymphopenia contributing to the development of bronchiolo-alveolar carcinoma through a loss of immunologic surveillance is discussed

  13. Adrenal function in asthmatic children treated with inhaled budesonide

    Bisgaard, H; Pedersen, S; Damkjaer Nielsen, M

    1991-01-01

    The effect of the inhaled topical steroid budesonide on adrenal function was evaluated in 33 children (aged 7-15 years) with moderate bronchial asthma. The trial was designed as a prospective single-blind study of the effect of budesonide in daily doses of 200 microgram through 400 microgram to 800...... significantly during treatment with 800 microgram budesonide as compared to treatment with 200 microgram budesonide (95% confidence interval: 74%-112%). It is concluded, that budesonide is a topical steroid with a favourable ratio between topical and systemic effects in asthmatic children....

  14. Regional study of ventilation with inhaled xenon 133 in children

    Gaultier, C.; Mensch, B.; Gerbeaux, J.

    1975-01-01

    A regional exploration of pulmonary ventilation in a population of 104 infants and children by a study of distribution and washout of xenon 133 inhaled with rebreathing is carried out. The results are expressed by photographs (gamma-camera) and time-activity curves. The indications for regional exploration were oriented by the existence on the straight X-ray film of a localised ventilation disorder (a hyperlucent area or an opacity). This study permitted physiopathological analysis and guided endobronchial examinations. The functional results obtained, complete and explain other methods of exploration of lung function by spirography, ventilatory mechanics, transthoracic electrical measurements and study of lung perfusion with technetium 99m [fr

  15. Inhalation Exposure Input Parameters for the Biosphere Model

    M. A. Wasiolek

    2003-09-24

    This analysis is one of the nine reports that support the Environmental Radiation Model for Yucca Mountain Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2003a) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents a set of input parameters for the biosphere model, and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the Total System Performance Assessment (TSPA) for a Yucca Mountain repository. This report, ''Inhalation Exposure Input Parameters for the Biosphere Model'', is one of the five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling, and the plan for development of the biosphere abstraction products for TSPA, as identified in the ''Technical Work Plan: for Biosphere Modeling and Expert Support'' (BSC 2003b). It should be noted that some documents identified in Figure 1-1 may be under development at the time this report is issued and therefore not available at that time. This figure is included to provide an understanding of how this analysis report contributes to biosphere modeling in support of the license application, and is not intended to imply that access to the listed documents is required to understand the contents of this analysis report. This analysis report defines and justifies values of mass loading, which is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Measurements of mass loading are used in the air submodel of ERMYN to calculate concentrations of radionuclides in air surrounding crops and concentrations in air

  16. Sudden death caused by 1,1-difluoroethane inhalation.

    Xiong, Zhenggang; Avella, Joseph; Wetli, Charles V

    2004-05-01

    A 20-year-old man was found dead on the floor next to a computer, with a nearly full can of "CRC Duster" dust remover located next to the deceased on the floor, and an empty can of the same product on the computer desk. Toxicologic evaluation using either gas chromatography/mass spectrometry (GC/MS) or gas chromatography/flame ionization detector (GC/FID) method identified the active ingredient 1,1-difluoroethane (Freon 152a) in all tissues analyzed. Tissue distribution studies revealed highest concentration in central blood, lung, and liver. It is believed that the 1,1-difluoroethane inhalation was the cause of death.

  17. Pulmonary lesions induced by inhaled plutonium in beagles

    Dagle, G.E.; Lund, J.E.; Park, J.F.

    1975-01-01

    The histopathologic features of pulmonary fibrosis and bronchiolo-alveolar carcinoma in beagles exposed to aerosols of plutonium oxide were reviewed. A hypothesis of the pathogenesis of radiation pneumonitis induced by inhalation of plutonium oxide was presented; this hypothesis included phagocytosis of plutonium particles, fibrosis responding to the necrosis, and alveolar cell hyperplasia compensating for alveolar cells killed by alpha radiation. Histopathologic features of the epithelial changes suggest a progression from hyperplasia to metaplasia and, finally, to bronchiolo-alveolar carcinoma. The possibility of concurrent radiation-induced lymphopenia contributing to the development of bronchiolo-alveolar carcinoma through a loss of immunologic surveillance was discussed

  18. Inhalation Exposure Input Parameters for the Biosphere Model

    M. A. Wasiolek

    2003-01-01

    This analysis is one of the nine reports that support the Environmental Radiation Model for Yucca Mountain Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2003a) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents a set of input parameters for the biosphere model, and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the Total System Performance Assessment (TSPA) for a Yucca Mountain repository. This report, ''Inhalation Exposure Input Parameters for the Biosphere Model'', is one of the five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the products (i.e., analysis and model reports) developed for biosphere modeling, and the plan for development of the biosphere abstraction products for TSPA, as identified in the ''Technical Work Plan: for Biosphere Modeling and Expert Support'' (BSC 2003b). It should be noted that some documents identified in Figure 1-1 may be under development at the time this report is issued and therefore not available at that time. This figure is included to provide an understanding of how this analysis report contributes to biosphere modeling in support of the license application, and is not intended to imply that access to the listed documents is required to understand the contents of this analysis report. This analysis report defines and justifies values of mass loading, which is the total mass concentration of resuspended particles (e.g., dust, ash) in a volume of air. Measurements of mass loading are used in the air submodel of ERMYN to calculate concentrations of radionuclides in air surrounding crops and concentrations in air inhaled by a receptor. Concentrations in air to which the

  19. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto

    2014-01-01

    fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...

  20. Agglomerate behaviour of fluticasone propionate within dry powder inhaler formulations.

    Le, V N P; Robins, E; Flament, M P

    2012-04-01

    Due to their small size, the respirable drug particles tend to form agglomerates which prevent flowing and aerosolisation. A carrier is used to be mixed with drug in one hand to facilitate the powder flow during manufacturing, in other hand to help the fluidisation upon patient inhalation. Depending on drug concentration, drug agglomerates can be formed in the mixture. The aim of this work was to study the agglomeration behaviour of fluticasone propionate (FP) within interactive mixtures for inhalation. The agglomerate phenomenon of fluticasone propionate after mixing with different fractions of lactose without fine particles of lactose (smaller than 32 μm) was demonstrated by the optical microscopy observation. A technique measuring the FP size in the mixture was developed, based on laser diffraction method. The FP agglomerate sizes were found to be in a linear correlation with the pore size of the carrier powder bed (R(2)=0.9382). The latter depends on the particle size distribution of carrier. This founding can explain the role of carrier size in de-agglomeration of drug particles in the mixture. Furthermore, it gives more structural information of interactive mixture for inhalation that can be used in the investigation of aerosolisation mechanism of powder. According to the manufacturing history, different batches of FP show different agglomeration intensities which can be detected by Spraytec, a new laser diffraction method for measuring aerodynamic size. After mixing with a carrier, Lactohale LH200, the most cohesive batch of FP, generates a lower fine particle fraction. It can be explained by the fact that agglomerates of fluticasone propionate with very large size was detected in the mixtures. By using silica-gel beads as ball-milling agent during the mixing process, the FP agglomerate size decreases accordingly to the quantity of mixing aid. The homogeneity and the aerodynamic performance of the mixtures are improved. The mixing aid based on ball

  1. Measurements of pulmonary ventilation following inhalation of Isovist trademark -300

    Thiele, J.; Kloeppel, R.

    1995-01-01

    A self-experiment was performed, in which representative planar images of the lungs were obtained using computerized tomography following inhalation of highly atomized isoosmolar contrast medium (Isovist-300 produced by the firm Schering). The administration of 2 ml contrast medium over 15 minutes was well tolerated by a healthy volunteer and caused no discomfort. The pattern of the contrast medium distribution was in accordance with that of regional ventilation. An increased density of peripheral vascular structures was not observed. The procedure can thus be regarded as an addition to the range of methods used in computerized tomography for measurements of pulmonary ventilation. (orig.) [de

  2. "My body breaks. I take solution." Inhalant use in Delhi as pleasure seeking at a cost.

    Gigengack, Roy

    2014-07-01

    Inhalant use has existed in India since the 1970s and has increased significantly over the last decades, especially among street-oriented young people. The latter constitute a heterogeneous category: children from street families, children 'of' the street, rag pickers, and part-time street children. There are also inhalant-using schoolchildren and young people in slums. Fieldwork was conducted for 1 year. Team ethnography, multi-sited and comparative research, flexibility of methods and writing field notes were explicit parts of the research design. Most research was undertaken with six groups in four areas of Delhi, exemplifying six generic categories of inhalant-using street-oriented young people. Inhalants in India are branded: Eraz-Ex diluter and whitener, manufactured by Kores, are used throughout Delhi; Omni glue in one specific area. There is a general lack of awareness and societal indifference towards inhalant use, with the exception of the inhalant users themselves, who possess practical knowledge. They conceive of inhalants as nasha, encapsulating the materiality of the substances and the experiential aspects of intoxication and addiction. Fragments of group interviews narrate the sensory appeal of inhalants, and an ethnographic vignette the dynamics of a sniffing session. These inhalant-using street children seek intoxication in a pursuit of pleasure, despite the harm that befalls them as a result. Some find nasha beautiful, notwithstanding the stigmatization, violence and bodily deterioration; others experience it as an overpowering force. A source of attraction and pleasure, inhalants ravage street children's lives. In this mysterious space of lived experience, their self-organization evolves. Distinguishing between hedonic and side effects, addiction helps to understand inhalant use as at once neurobiological, cultural, and involving agency. The implications are that India needs to develop a policy of treatment and employment to deal with the

  3. Does inhalation injury predict mortality in burns patients or require redefinition?

    Youngmin Kim

    Full Text Available Inhalation injury is known to be an important factor in predicting mortality in burns patients. However, the diagnosis is complicated by the heterogeneous presentation and inability to determine the severity of inhalation injury. The purpose of this study was to identify clinical features of inhalation injury that affect mortality and the values that could predict the outcome more precisely in burns patients with inhalation injury. This retrospective observational study included 676 burns patients who were over 18 years of age and hospitalized in the Burns Intensive Care Unit between January 2012 and December 2015. We analyzed variables that are already known to be prognostic factors (age, percentage of total body surface area (%TBSA burned, and inhalation injury and factors associated with inhalation injury (carboxyhemoglobin and PaO2/FiO2 [PF] ratio by univariate and multivariate logistic regression. Age group (odds ratio [OR] 1.069, p<0.001, %TBSA burned (OR 1.100, p<0.001, and mechanical ventilation (OR 3.774, p<0.001 were identified to be significant predictive factors. The findings for presence of inhalation injury, PF ratio, and carboxyhemoglobin were not statistically significant in multivariate logistic regression. Being in the upper inhalation group, the lower inhalation group, and having a PF ratio <100 were identified to be significant predictors only in univariate logistic regression analysis (OR 4.438, p<0.001; OR 2.379, p<0.001; and OR 2.765, p<0.001, respectively. History and physical findings are not appropriate for diagnosis of inhalation injury and do not predict mortality. Mechanical ventilation should be recognized as a risk factor for mortality in burns patients with inhalation injury.

  4. In vitro dose comparison of Respimat® inhaler with dry powder inhalers for COPD maintenance therapy

    Ciciliani A

    2017-05-01

    Full Text Available Anna-Maria Ciciliani,1,2 Peter Langguth,1 Herbert Wachtel2 1Institute of Pharmacy and Biochemistry, Faculty 09 (Chemistry, Pharmaceutics and Geosciences, Johannes Gutenberg University, Mainz, 2Analytical Development Department, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Background: Combining in vitro mouth–throat deposition measurements, cascade impactor data and computational fluid dynamics (CFD simulations, four different inhalers were compared which are indicated for chronic obstructive pulmonary disease (COPD treatment.Methods: The Respimat inhaler, the Breezhaler, the Genuair, and the Ellipta were coupled to the idealized Alberta throat model. The modeled dose to the lung (mDTL was collected downstream of the Alberta throat model using either a filter or a next generation impactor (NGI. Idealized breathing patterns from COPD patient groups – moderate and very severe COPD – were applied. Theoretical lung deposition patterns were assessed by an individual path model.Results and conclusion: For the Respimat the mDTL was found to be 59% (SD 5% for the moderate COPD breathing pattern and 67% (SD 5% for very severe COPD breathing pattern. The percentages refer to nominal dose (ND in vitro. This is in the range of 44%–63% in vivo in COPD patients who display large individual variability. Breezhaler showed a mDTL of 43% (SD 2% for moderate disease simulation and 51% (SD 2% for very severe simulation. The corresponding results for Genuair are mDTL of 32% (SD 2% for moderate and 42% (SD 1% for very severe disease. Ellipta vilanterol particles showed a mDTL of 49% (SD 3% for moderate and 55% (SD 2% for very severe disease simulation, and Ellipta fluticasone particles showed a mDTL of 33% (SD 3% and 41% (SD 2%, respectively for the two breathing patterns. Based on the throat output and average flows of the different inhalers, CFD simulations were performed. Laminar and turbulent steady flow calculations indicated that

  5. Adherence to tobramycin inhaled powder vs inhaled solution in patients with cystic fibrosis: analysis of US insurance claims data

    Hamed K

    2017-04-01

    Full Text Available Kamal Hamed,1 Valentino Conti,2 Hengfeng Tian,1 Emil Loefroth3 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Global Service Center, Dublin, Ireland; 3Novartis Sverige AB, Täby, Sweden Purpose: Tobramycin inhalation powder (TIP, the first dry-powder inhaled antibiotic for pulmonary Pseudomonas aeruginosa infection, is associated with reduced treatment burden, increased patient satisfaction, and higher self-reported adherence for cystic fibrosis (CF patients. We compared adherence in CF patients newly treated with TIP with those newly treated with the traditional tobramycin inhalation solution (TIS, using US insurance claims data.Patients and methods: From the Truven MarketScan® database, we identified CF patients chronically infected with P. aeruginosa who had been prescribed TIP between May 1, 2013 to December 31, 2014, or TIS between September 1, 2010 to April 30, 2012 with at least 12 months of continuous medical and pharmacy benefits prior to and following prescription. TIP and TIS adherence levels were assessed.Results: A total of 145 eligible patients were identified for the TIP cohort and 306 for the TIS cohort. Significant differences in age distribution (25.0 vs 21.9 years for TIP vs TIS, respectively, P=0.017, type of health plan (P=0.014, employment status (72.4% vs 63.4% of TIP vs TIS patients in full-time employment, P=0.008, and some comorbidities were observed between the two cohorts. Although a univariate analysis found no significant differences between TIP and TIS (odds ratio [OR] 1.411, 95% confidence interval [CI] 0.949–2.098, TIP was moderately associated with higher adherence levels compared with TIS in a multivariable analysis, once various demographic and clinical characteristics were adjusted for. These included geographic location (OR: 1.566, CI: 1.016–2.413 and certain comorbidities.Conclusion: This study of US patient data supports previous findings that TIP is associated with better

  6. Clinical effectiveness of the Respimat® inhaler device in managing chronic obstructive pulmonary disease: evidence when compared with other handheld inhaler devices

    et al

    2011-02-01

    Full Text Available Felix SF Ram1, Celso R Carvallho2, John White31School of Health and Social Services, Massey University, Auckland, New Zealand; 2Department of Physical Therapy, School of Medicine, University of São Paulo, Brazil; 3York Hospitals NHS Foundation Trust, York Hospital, York, UKObjectives: Medication for the management of chronic obstructive pulmonary disease (COPD may be delivered by a number of different inhaler devices. This study was undertaken to determine the clinical effectiveness of the Respimat® handheld inhaler device compared with other handheld inhaler devices for the delivery of medication in stable COPD.Methodology: A systematic review of high-quality randomized controlled clinical trials comparing Respimat with other inhaler devices using the same medication was performed. Studies were searched for in the Cochrane Central Register of Controlled Trials as well as other relevant electronic databases. Manufacturers of inhaled COPD medication were also contacted for potential trials.Results: Seven studies of high methodological quality with 3813 participants were included in the review. Three trials used Handihaler® as the comparator inhaler, three used a chlorofluorocarbon metered-dose inhaler (CFC-MDI, and one trial used a hydroflouroalkane (HFA-MDI. When Respimat was compared with Handihaler, the following reported outcomes were not significantly different: trough forced expiratory volume in 1 second (FEV1 (weighted mean difference [WMD] 0.01 L; P = 0.14, trough forced vital capacity (FVC (WMD 0.001 L: P = 0.88, peak FEV1 (WMD 0.01 L: P = 0.08, peak FVC (WMD 0.01 L: P = 0.55, morning peak expiratory flow rate (PEFR (WMD 5.06 L/min: P = 0.08, and evening PEFR (WMD 4.39 L/min: P = 0.15. Furthermore, there were no differences when Respimat was compared with Handihaler for risk of exacerbations (relative risk [RR] 0.94: P = 0.81, dry mouth (RR 1.57: P = 0.34, or nasopharyngitis (RR 1.42: P = 0.22. For Respimat compared with CFC-MDI, the

  7. Individual monitoring program for internal contamination by inhaled uranium

    Vazquez, C.; Chapel, M.L.; Saenz Gancedo, R.

    1988-01-01

    The metabolic behaviour of inhaled uranium is studied. Using a particular analytical method applied to the models and dose assessment methods recommended by ICRP, the organ committed equivalent dose and effective equivalent dose are calculated. The exact ALI and DAC are derived from there. In the paper, the influence that various parameters have on those results are considered for the specific case of a particular nuclear element fabrication factory. Different AMAD and solubility type of inhaled material are specially analyzed. The results show the paramount importance of some of these parameters on the secondary and derived dose limits. Relationships between the real intake, as a fraction of ALI, and the lung retention or urine excretion are shown for different cases and intake forms hypothesis. Minimum detectable intakes with the available experimental techniques are then established. The results shown in the papel are a useful tool to help on the decision on the type and frequency of the individual monitoring techniques to be established in different circumstances. (Author)

  8. Dose-effect studies with inhaled plutonium nitrate in dogs

    Dagle, G.E.; Cannon, W.C.; Case, A.C.; Madison, R.M.; McShane, J.F.; Stevens, D.L.; Rowe, S.E.; Ragan, H.A.; Schirmer, R.E.

    1980-01-01

    Beagle dogs given a single inhalation exposure to 239 Pu(NO 3 ) 4 , and observed for life-span dose-effect relationship, died from radiation pneumonitis (four of five at the highest dosage level, in 14 to 25 mo postexposure; 1 of 20 at the medium-high dosage level, at 34 mo postexposure). There were also indications in these dogs of radiation osteosis, characterized by peritrabecular fibrosis. One dog, at 39 mo postexposure, has radiographic evidence of an osteosarcoma. Leukopenia, lymphopenia, neutropenia and decreased numbers of circulating monocytes and eosinophils occurred at the two highest dosage levels, as previously reported (Annual Report, 1978). Twelve dogs given a single inhalation exposure to 238 Pu(NO 3 ) 4 showed a more rapid translocation of 238 Pu(NO 3 ) 4 to bone and liver than was observed for 239 Pu(NO 3 ) 4 , but at 1 yr postexposure the percentage of the final body burden in bone and liver were similar for the two isotopes

  9. Rhabdomyolysis with acute tubular necrosis following occupational inhalation of thinners.

    Ngajilo, D; Ehrlich, R

    2017-07-01

    Thinners are mixtures of organic solvents commonly containing toluene, xylene, acetone, hexane, benzene and methyl isobutyl ketone. This report describes a case of rhabdomyolysis with acute tubular necrosis and renal failure, most likely attributable to toluene, following occupational exposure to thinners while cleaning a steel water tank. These adverse health effects have previously been reported following acute poisoning or intentional inhalation by drug abusers, but rarely in the occupational setting. Poor working conditions, lack of health and safety training and delayed treatment contributed to the onset and severity of the patient's complications. This case emphasizes the need for strict control measures, including adequate ventilation, training on working in confined spaces, appropriate personal protective equipment and emergency rescue procedures in such settings. In addition, rhabdomyolysis, acute tubular necrosis and renal failure should be added to safety data material as possible complications of excessive inhalation of thinners. © The Author 2017. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Generation and characterization of cyclosporine aerosols for administration by inhalation

    Hoover, M.D.; Muggenburg, B.A.; Snipes, M.B.; Wolff, R.K.; Yeh, H.C.; Griffith, B.P.; Burckart, G.J.; Mauderly, J.L.

    1988-01-01

    A method was developed for generating aerosols of the immunosuppressive agent cyclosporine and a gamma-emitting radiolabel ( 99m Tc) for administration by inhalation. Cyclosporine was dissolved in ethyl alcohol (EtOH) and nebulized with a Love- lace nebulizer operated with 50 psi compressed air. For a cyclosporine concentration of 25 mg/mL, the particle size of the aerosol was 0.7 μm activity median aerodynamic diameter (AMAD), with 1.8 geometric standard deviation (GSD). The clear solution of EtOH and cyclosporine became a cloudy suspension when a limited amount of saline solution containing a 99m Tc radiolabel was added. This occurred because cyclosporine is hydrophobic. If saline concentrations as high as 6% in EtOH by volume were used, a gummy residue formed in the nebulizer and the particle aerodynamic diameter became unacceptably large (4.7 μm). When the saline concentration was only 3 % (the minimum radiolabel volume needed for gamma camera studies of lung deposition), the suspensions of cyclosporine could be nebulized to give a particle size of 2.2 μm AMAD with 2.1 GSD. The radiolabel was uniformly distributed with the spherical cyclosporine particles. Concentrations and particle size distributions remained constant over 1-h generation periods. These aerosols have been used in inhalation studies with Beagle dogs. (author)

  11. Life-span studies of inhaled plutonium in beagle dogs

    Bair, W.J.

    1990-04-01

    In 1970 a life-span study with over 300 beagle dogs was begun to gain an understanding of long-term health effects resulting from respiratory tract intakes of plutonium and to derive risk estimates that might be applied to plutonium and other transuranic elements. Groups of beagle dogs were given single exposures to 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 to obtain graded levels of initial lung burdens ranging from 1 to 1800 Bq lung. The objective of this paper is to give you a progress report on the current life-span studies of inhaled plutonium in beagle dogs at the Pacific Northwest Laboratory. I will describe the biokinetics of inhaled plutonium in dogs and the resulting health effects. I will also mention some studies directed towards understanding the mechanism leading to these effects. Finally, I will discuss the current risk estimates derived from these studies and how they might relate to plutonium exposures in humans. 5 refs., 13 figs., 4 tabs

  12. Inhaled iloprost for the treatment of pulmonary hypertension

    H. Olschewski

    2009-03-01

    Full Text Available Prostacyclin and its analogues (prostanoids are potent vasodilators, and exhibit antithrombotic, antiproliferative and anti-inflammatory properties. Pulmonary arterial hypertension (PAH is characterised by vasoconstriction, thrombosis and proliferation, and is associated with reduced synthesis of endogenous prostacyclin. This provides a strong rationale for the use of prostanoids to treat PAH, a concept that is now supported by more than two decades of clinical research and experience. Intravenous and subcutaneous prostanoids have clearly demonstrated efficacy in severe PAH, but adverse events related to the drug delivery system, systemic side-effects and tachyphylaxis have driven research into alternative prostanoid treatments. Iloprost is administered by inhalation, and thus avoids most of the systemic side-effects associated with i.v. or subcutaneous prostanoid infusion. Two randomised controlled 12-week trials in patients with PAH have demonstrated efficacy and a favourable safety profile for iloprost as monotherapy (the AIR trial and in combination with oral bosentan (STEP. Open-label uncontrolled long-term studies of inhaled iloprost therapy indicate that this treatment may improve long-term outcomes in PAH.

  13. The modelling of external exposure and inhalation pathways in COSYMA

    Brown, J.; Simmonds, JR.; Ehrhardt, J.; Hasemann, I.

    1991-01-01

    Following an accidental release of radionuclides to atmosphere the major direct exposure pathways of concern are: external irradiation from material in the cloud; internal exposure following inhalation of material in the cloud; external irradiation from material deposited on the ground; and external irradiation due to contamination of skin and clothes. In addition material resuspended from the ground can be inhaled and lead to internal exposure. In this paper the way that these exposure pathways are modelled in COSYMA is described. At present in COSYMA external exposure from deposited material is modelled using a dataset of doses per unit deposit of various radionuclides. This dataset, is based on activity deposited on undisturbed soil. The basic data are for doses outdoors and shielding factors are used to estimate doses for people indoors. Various groups of people spending different amounts of time indoors and out can be considered and shielding factors appropriate to three building types can be adopted. A more complex model has also been developed to predict radiation exposure following deposition to different surfaces in the environment. This model called EXPURT is briefly described in this paper. Using EXPURT, doses as a function of time after a single deposit have been calculated for people living in three types of area. These results are described in the paper and compared with those that are currently used in COSYMA. The paper will also discuss what future work is required in this area and the adequacy of existing models

  14. Development of high efficiency ventilation bag actuated dry powder inhalers.

    Behara, Srinivas R B; Longest, P Worth; Farkas, Dale R; Hindle, Michael

    2014-04-25

    New active dry powder inhaler systems were developed and tested to efficiently aerosolize a carrier-free formulation. To assess inhaler performance, a challenging case study of aerosol lung delivery during high-flow nasal cannula (HFNC) therapy was selected. The active delivery system consisted of a ventilation bag for actuating the device, the DPI containing a flow control orifice and 3D rod array, and streamlined nasal cannula with separate inlets for the aerosol and HFNC therapy gas. In vitro experiments were conducted to assess deposition in the device, emitted dose (ED) from the nasal cannula, and powder deaggregation. The best performing systems achieved EDs of 70-80% with fine particle fractions <5 μm of 65-85% and mass median aerodynamic diameters of 1.5 μm, which were target conditions for controlled condensational growth aerosol delivery. Decreasing the size of the flow control orifice from 3.6 to 2.3mm reduced the flow rate through the system with manual bag actuations from an average of 35 to 15LPM, while improving ED and aerosolization performance. The new devices can be applied to improve aerosol delivery during mechanical ventilation, nose-to-lung aerosol administration, and to assist patients that cannot reproducibly use passive DPIs. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Ferrocene: Disposition following nose-only inhalation by the rat

    Slauter, R.W.; Tippin, T.K.; Jeffcoat, A.R.; Matthews, H.B.

    1990-01-01

    Ferrocene (FCN) is a volatile solid organometallic proposed for use as an anti-knock additive in gasoline. Such use would provide significant potential for human exposure via inhalation. Nose-only exposure of male F344 rats over 6 h to constant concentrations of 5 and 25 ng of [ 14 C]FCN/mL air was conducted by blending correct proportions of an air stream concentrated with [ 14 C]FCN vapor with one that was FCN free. Fractional pulmonary absorption of FCN was estimated to be ca. 66 and 55% with concentrations of 14 C in blood increasing steadily throughout the exposure period to 80 and 370 ng-eq of FCN/mL, respectively. Disappearance of 14 C from the blood was multiphasic (terminal t 1/2 =∼2 d) following inhalation exposure, resulting in blood concentrations of 10 and 50 ng-eq of FCN/mL 72 h after end of exposure. More than 80% of the recovered 14 C was in the 0-72 h urine, approximately half of which was a single metabolite (radio-HPLC). Unchanged FCN was excreted in only minor amounts ( 14 C were also excreted in feces (ca. 10% of total) and breath (ca. 4% of total). Neither lung nor nasopharynx had tissue to blood ratios of 14 C>3 72 h after exposure. Similar disposition was shown after an iv bolus of 1.0 mg of [ 14 C]FCN/kg body weight

  16. Lung dosimetry for inhaled radon progeny in smokers

    Baias, P. F.; Hofmann, W.; Winkler-Heil, R.; Cosma, C.; Duliu, O. G.

    2010-01-01

    Cigarette smoking may change the morphological and physiological parameters of the lung. Thus the primary objective of the present study was to investigate to what extent these smoke-induced changes can modify deposition, clearance and resulting doses of inhaled radon progeny relative to healthy non-smokers (NSs). Doses to sensitive bronchial target cells were computed for four categories of smokers: (1) Light, short-term (LST) smokers, (2) light, long-term (LLT) smokers, (3) heavy, short-term (HST) smokers and (4) heavy, long-term (HLT) smokers. Because of only small changes of morphological and physiological parameters, doses for the LST smokers hardly differed from those for NSs. For LLT and HST smokers, even a protective effect could be observed, caused by a thicker mucus layer and increased mucus velocities. Only in the case of HLT smokers were doses higher by about a factor of 2 than those for NSs, caused primarily by impaired mucociliary clearance, higher breathing frequency, reduced lung volume and airway obstructions. These higher doses suggest that the contribution of inhaled radon progeny to the risk of lung cancer in smokers may be higher than currently assumed on the basis of NS doses. (authors)

  17. Starting with a higher dose of inhaled corticosteroids in primary care asthma treatment

    van der Molen, T; Meyboom-de Jong, B; Mulder, HH; Postma, DS

    New British guidelines on the treatment of asthma (9) advocate starting with a higher dose of inhaled corticosteroids in newly detected asthma patients. We investigated whether initiating inhaled steroid treatment with a higher dose is clinically more effective than a lower dose in steroid naive

  18. The impact of large tidal volume ventilation on the absorption of inhaled insulin in rabbits

    Petersen, Astrid Heide; Laursen, Torben; Ahrén, Bo

    2007-01-01

    Previous studies have shown that ventilation patterns affect absorption of inhaled compounds. Thus, the aim of this study was to investigate the effect of large tidal volume ventilation (LTVV) on the absorption of inhaled insulin in rabbits. Mechanically ventilated rabbits were given human insulin...

  19. Inhalant and Prescription Medication Abuse among Adolescents: An Inexpensive, Accessible, and Misperceived Trend

    Sikes, April; Walley, Cynthia; McBride, Rebecca; Fusco, Angela; Cole, Rebekah F.; Lauka, Justin

    2011-01-01

    Inhalant and prescription medication abuse, particularly among adolescents, are serious problems in our society. Several risk factors associated with inhalant and medication abuse among adolescents have been identified. As a result, adolescents may suffer multiple consequences in a range of developmental areas. The purpose of this article is to…

  20. The effect of exercise on the absorption of inhaled human insulin in healthy volunteers

    Petersen, Astrid Heide; Kohler, Gerd; Korsatko, Stefan

    2008-01-01

    overall absorption. Aims To investigate the effect of moderate exercise on the absorption of inhaled insulin. Methods A single-centre, randomized, open-label, three-period cross-over trial was carried out in 12 nonsmoking healthy subjects. A dose of 3.5 mg inhaled human insulin was administered via...

  1. Human lung epithelial cell cultures for analysis of inhaled toxicants: Lessons learned and future directions

    Hiemstra, P.S.; Grootaers, G.G.; Does, A.M. van der; Krul, C.A.M.; Kooter, I.M.

    2018-01-01

    The epithelium that covers the conducting airways and alveoli is a primary target for inhaled toxic substances, and therefore a focus in inhalation toxicology. The increasing concern about the use of animal models has stimulated the development of in vitro cell culture models for analysis of the

  2. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine (also...

  3. Investigation of the applicability of dry powder inhalation in school children

    Lexmond, A. J.; Kruizinga, T. J.; Hagedoorn, P.; Frijlink, H. W.; Rottier, B. L.; de Boer, A. H.

    2013-01-01

    Children are an important target group for inhalation therapy, but little is known about their intellectual and inspiratory capacities to operate dry powder inhalers (DPIs). Most studies so far have focused either on a specific DPI, or on (single) inhala- tion parameters and how these are affected

  4. Prescription of inhalers in asthma and COPD: Towards a rational, rapid and effective approach

    Dekhuijzen, P.N.R.; Vincken, W.; Virchow, J.C.; Roche, N.; Agusti, A.; Lavorini, F.; Aalderen, W.M.; Price, D.

    2013-01-01

    Inhaled medication is the cornerstone of the pharmacological treatment of patients with asthma and COPD. The major two classes of inhaled medication include corticosteroids (ICS) and bronchodilators. There is a wide diversity in molecules in both classes. Moreover, there is a wide variation in

  5. Inhalant drug use and street youth : Ethnographic insights from Mexico City

    Gigengack, Roy; Preedy, Victor

    2016-01-01

    The inhalation of volatile substances with intentions of intoxication affects the lives of marginalized youths around the globe, but remains poorly understood. Based upon long-term ethnographic enquiry, this chapter describes the inhalant use of Mexico City's young street people from their

  6. Inhalation anesthesia in dumeril´s monitor with isofluane, sevofluane, and nitrus oxide

    Bertelsen, Mads Frost; Mosley, Craig; Crawshaw, Graham J.

    2005-01-01

    Induction and recovery from inhalation anesthesia of Dumeril´s monitors using isoflurane, sevoflurane and nitrus oxide were characterized using a randomized crossover design.......Induction and recovery from inhalation anesthesia of Dumeril´s monitors using isoflurane, sevoflurane and nitrus oxide were characterized using a randomized crossover design....

  7. DERMAL, ORAL, AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

    Methyl tertiary butyl ether (MTBE), a gasoline additive, used to increase octane and reduce carbon monoxide emissions and ozone precursors has contaminated drinking water leading to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation ki...

  8. DERMAL, ORAL AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY-BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

    Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhal...

  9. Passive smoking of cigarettes compared to inhalation of exhaust gases; Meeroken door uitlaatgassen

    Van Doorn, R. [Afdeling Medische Milieukuinde, GGD Rotterdam en omstreken, Rotterdam (Netherlands)

    2002-09-01

    A comparison has been made between the consequences of inhaling exhaust gases and passive smoking of cigarettes. In both cases it concerns the inhalation of combustion products with irritating and toxic properties. [Dutch] Er is een vergelijking gemaakt tussen de gevolgen van het inademen van uitlaatgassen en het meeroken van sigaretten. In biede gevallen gaat het om verbrandingsproducten met irriterende en toxische eigenschappen.

  10. Foreign Body Inhalation: A Review of Patients at the Korle Bu ...

    BACKGROUND: Foreign body inhalation, a surgical emergency requiring prompt management to avoid morbidity and mortality , poses a diagnostic and management challenge to otolaryngologists. OBJECTIVE: To assess the pattern of foreign body inhalation at the ENT Unit Korle Bu Teaching Hospital Accra, Ghana.

  11. The effect of body posture during medication inhalation on exercise induced bronchoconstriction in asthmatic children

    Visser, R.; Wind, M.; de Graaf, B.J.; de Jong, F.H.; van der Palen, Jacobus Adrianus Maria; Thio, B.J.

    2015-01-01

    RATIONALE: Inhaling medication in a standard body posture leads to impaction of particles in the sharp angle of the upper airway. Stretching the upper airway by extending the neck in a forward leaning body posture may improve pulmonary deposition. A single dose of inhaled corticosteroids (ICS)

  12. Problems of dosimetry and risk assessment associated with inhalation of fuel particles

    Repin, V.S.; Nechaev, S.Y.; Bondarenko, O.A.; Bykorez, A.I.; Kononenko, L.I.

    1995-01-01

    This work deals with the problems of dosimetry and risk assessment associated with inhalation of fuel particles. Radioactive emission parameters and potential for assessment of the lung cancer risk with inhalation penetration of hot particles are described. (O.L.). 10 refs., 9 figs., 1 tab

  13. Prescription of inhalers in asthma and COPD: towards a rational, rapid and effective approach

    Dekhuijzen, P. N. R.; Vincken, W.; Virchow, J. C.; Roche, N.; Agusti, A.; Lavorini, F.; van Aalderen, W. M.; Price, D.

    2013-01-01

    Inhaled medication is the cornerstone of the pharmacological treatment of patients with asthma and COPD. The major two classes of inhaled medication include corticosteroids (ICS) and bronchodilators. There is a wide diversity in molecules in both classes. Moreover, there is a wide variation in

  14. Dry powder inhalation of hemin to induce heme oxygenase expression in the lung

    Zijlstra, G.S.; Brandsma, C.; Harpe, M.F.H.; Van Dam, G.M.; Slebos, D.J.; Kerstjens, H.A.M.; de Boer, Anne; Frijlink, H.W.

    2007-01-01

    The purpose of this study was to formulate hemin as a powder for inhalation and to show proof of concept of heme oxygenase 1 (HO-1) expression in the lungs of mice by inhalation of hemin. Hemin was spray dried from a neutralized sodium hydroxide solution. The particle size distribution of the powder

  15. Anxiety symptoms in crack cocaine and inhalant users admitted to a psychiatric hospital in southern Brazil.

    Zubaran, Carlos; Foresti, Katia; Thorell, Mariana Rossi; Franceschini, Paulo Roberto

    2013-01-01

    The occurrence of psychiatric comorbidity among individuals with crack or inhalant dependence is frequently observed. The objective of this study was to investigate anxiety symptoms among crack cocaine and inhalant users in southern Brazil. The study investigated two groups of volunteers of equal size (n=50): one group consisted of crack cocaine users, and the other group consisted of inhalant users. Research volunteers completed the Portuguese versions of the State-Trait Anxiety Inventory (STAI), Hamilton Anxiety Rating Scale (HAM-A), and Self-Report Questionnaire (SRQ). Both crack and inhalant users experience significant symptoms of anxiety. Inhalant users presented significantly more anxiety symptoms than crack users according to the HAM-A questionnaire only. In contrast to the results of the HAM-A, the STAI failed to demonstrate a significant difference between the two groups of substance users. SRQ scores revealed that crack and inhalants users had significant degrees of morbidity. A significant difference regarding anxiety symptomatology, especially state anxiety, was observed among inhalant and crack users. Anxiety and overall mental psychopathology were significantly correlated in this sample. The results indicate that screening initiatives to detect anxiety and additional psychiatric comorbidities among crack and inhalant users are feasible and relevant. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  16. Propositions for the implementation and reinforcement of surveillance activities of exposure and risks associated to radon inhalation

    2003-10-01

    This report treats exclusively of exposure by inhalation. It expresses the propositions relative to the implantation and the development of an information network allowing to characterize the radon exposures by inhalation and associated risks. (N.C.)

  17. Prenatal Inhalation Exposure to Evaporative Condensates of Gasoline with 15% Ethanol and Evaluation of Sensory Function in Adult Rat Offspring

    The introduction of ethanol-blended automotive fuels has raised concerns about potential health effects from inhalation exposure to the combination of ethanol and gasoline hydrocarbon vapors. Previously, we evaluated effects of prenatal inhalation exposure to 100% ethanol (E100) ...

  18. Experimental study of contamination by inhalation of radioactive iodine aerosols. Biological balance; Etude experimentale de la contamination par inhalation d'aerosols d'iode radioactif bilan biologique

    Marble, G [Commissariat a l' Energie Atomique, 92 - Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1968-07-01

    Several articles have been published concerning research into contamination produced by inhalation of radioactive iodine aerosols in monkeys. Results dealing with the biological balance of this contamination are presented and discussed in this report. (author) [French] L'etude experimentale de la contamination par inhalation d'aerosols d'iode radioactif effectuee chez le singe a fait l'objet de plusieurs publications. Les resultats concernant le bilan biologique de cette contamination sont presentes et discutes dans ce rapport. (auteur)

  19. Cigarettes, lung cancer, and coronary heart disease: the effects of inhalation and tar yield.

    Higenbottam, T; Shipley, M J; Rose, G

    1982-06-01

    Ten-year mortality rates for lung cancer and coronary heart disease have been related to cigarette smoking habits in 17 475 male civil servants aged 40-64 and in sample of 8089 male British residents aged 35-69. Both diseases were more frequent in smokers. Lung cancer rates were higher overall for "non-inhalers", particularly in heavy smokers. Tar yield correlated with the risk of lung cancer in non-inhalers but less so in inhalers. Conversely, coronary deaths were more common among inhalers, and the effect of tar/nicotine yield (such as it was) was confined to inhalers. It appears that there are subtle interactions between the amount smoked, the tar/nicotine yield of the cigarette, and the style of smoking. Thus the effects of a change in cigarette characteristics are hard to predict, and they may be different for respiratory and cardiovascular disease.

  20. Real-time measurement of inhaled and exhaled cigarette smoke: Implications for dose

    McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John, E-mail: conor_mcgrath@bat.co [British American Tobacco, Group R and D Centre, Southampton, SO15 8TL (United Kingdom)

    2009-02-01

    Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of 150 -- 250 nm count median diameter (CMD). Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, the average CMD of inhaled smoke was 160 nm while the average CMD of exhaled smoke was 239 nm with an average growth factor of 1.5.

  1. Preliminary experience with combined inhaled milrinone and prostacyclin in cardiac surgical patients with pulmonary hypertension.

    Laflamme, Maxime; Perrault, Louis P; Carrier, Michel; Elmi-Sarabi, Mahsa; Fortier, Annik; Denault, André Y

    2015-02-01

    To retrospectively evaluate the effects of combined inhaled prostacyclin and milrinone to reduce the severity of pulmonary hypertension when administered prior to cardiopulmonary bypass. Retrospective case control analysis of high-risk patients undergoing cardiac surgery. Single cardiac center. Sixty one adult cardiac surgical patients with pulmonary hypertension, 40 of whom received inhalation therapy. Inhaled milrinone and inhaled prostacyclin were administered before cardiopulmonary bypass (CPB). Administration of both inhaled prostacyclin and milrinone was associated with reductions in central venous pressure, and mean pulmonary artery pressure, increases in cardiac index, heart rate, and the mean arterial-to-mean pulmonary artery pressure ratio (p milrinone before CPB was associated with a reduction in the severity of pulmonary hypertension. In addition, a significant reduction in vasoactive support in the intensive care unit during the first 24 hours after cardiac surgery was observed. The impact of this strategy on postoperative survival needs to be determined. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Quantification of inhaled aerosol particles composed of toxic household disinfectant using radioanalytical method.

    Shim, Ha Eun; Lee, Jae Young; Lee, Chang Heon; Mushtaq, Sajid; Song, Ha Yeon; Song, Lee; Choi, Seong-Jin; Lee, Kyuhong; Jeon, Jongho

    2018-05-25

    To assess the risk posed by a toxic chemical to human health, it is essential to quantify its uptake in a living subject. This study aims to investigate the biological distribution of inhaled polyhexamethylene guanidine (PHMG) aerosol particle, which is known to cause severe pulmonary damage. By labeling with indium-111 ( 111 In), we quantified the uptake of PHMG for up to 7 days after inhalation exposure in rats. The data demonstrate that PHMG is only slowly cleared, with approximately 74% of inhaled particles persisting in the lungs after 168 h. Approximately 5.3% of inhaled particles were also translocated to the liver after 168 h, although the level of redistribution to other tissues, including the kidneys and spleen, was minimal. These observations suggest that large uptake and slow clearance may underlie the fatal inhalation toxicity of PHMG in humans. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Inhalation Toxicology Research Institute annual report, October 1, 1982-September 30, 1983

    1983-12-01

    The mission of the Inhalation Toxicology Research Institute (ITRI) is to investigate the nature and magnitude of human health effects that might result from inhalation of airborne materials encountered in the work place, special attention is directed toward airborne particulate and gaseous emissions released by various energy technologies or from national defense activities. Included are five papers on the physical and chemical characterization of energy technology aerosols, 10 papers on laboratory studies of aerosol generation and characterization, 11 papers on in vitro predictors of toxicity, 12 papers on disposition and fate of inhaled materials, 24 papers on dose-response relationships for inhaled radionuclides, 3 papers on dose-response relationships for inhaled chemical toxicants, 8 papers on biological factors that influence dose-response relationships, and 4 papers are concerned with risk assessment

  4. Dose-Dependent Protective Effect of Inhalational Anesthetics Against Postoperative Respiratory Complications

    Grabitz, Stephanie D; Farhan, Hassan N; Ruscic, Katarina J

    2017-01-01

    OBJECTIVES: Inhalational anesthetics are bronchodilators with immunomodulatory effects. We sought to determine the effect of inhalational anesthetic dose on risk of severe postoperative respiratory complications. DESIGN: Prospective analysis of data on file in surgical cases between January 2007...... with endotracheal intubation. INTERVENTIONS: Median effective dose equivalent of inhalational anesthetics during surgery (derived from mean end-tidal inhalational anesthetic concentrations). MEASUREMENTS AND MAIN RESULTS: Postoperative respiratory complications occurred in 6,979 of 124,497 cases (5.61%). High...... inhalational anesthetic dose of 1.20 (1.13-1.30) (median [interquartile range])-fold median effective dose equivalent versus 0.57 (0.45-0.64)-fold median effective dose equivalent was associated with lower odds of postoperative respiratory complications (odds ratio, 0.59; 95% CI, 0.53-0.65; p

  5. Basic study on positive effects of radon inhalation on pet's health

    Kataoka, Takahiro; Sakoda, Akihiro; Kawabe, Atsushi; Hanamoto, Katsumi; Yamaoka, Kiyonori; Tokunaga, Rikizo

    2012-01-01

    Radon inhalation using our radon exposure device activated anti-oxidative function in some organs of mouse. To assess the possibility of its application to veterinary care, healthy dogs and cats with chronic renal failure were inhaled radon at a concentration of 5500 Bq/m 3 for 30 minutes every 2 days for 30 days. In result, radon inhalation within a relatively long time period significantly decreased the triglyceride level of dogs. On the other hand, some cats increased the volume of drinking water by radon inhalation and the creatinine level in blood of these cats was decreased to normal level. These findings suggest that radon inhalation may have curative properties against chronic renal failure. (author)

  6. Real-time measurement of inhaled and exhaled cigarette smoke: Implications for dose

    McGrath, Conor; Warren, Nigel; Biggs, Philip; McAughey, John

    2009-01-01

    Inhalation of tobacco smoke aerosol is a two-step process involving puffing followed by inhalation. Measured smoke deposition efficiencies in the lung (20-70%) are greater than expected for smoke particles of 150 -- 250 nm count median diameter (CMD). Various mechanisms have been put forward to explain this enhanced deposition pattern, including coagulation, hygroscopic growth, condensation and evaporation, changes in composition, or changes in inhalation behaviour. This paper represents one of a series of studies seeking to better quantify smoke chemistry, inhalation behaviour and cumulative particle growth. The studies have been conducted to better understand smoke dosimetry and links to disease as part of a wider programme defining risk and potential harm reduction. In this study, the average CMD of inhaled smoke was 160 nm while the average CMD of exhaled smoke was 239 nm with an average growth factor of 1.5.

  7. Reversibility of pulmonary function after inhaling salbutamol in different doses and body postures in asthmatic children.

    Visser, R; Kelderman, S; de Jongh, F H C; van der Palen, J; Thio, B J

    2015-10-01

    Pulmonary medication is often delivered in the form of medical aerosols designed for inhalation. Recently, breath actuated inhalers (BAI's) gained popularity as they can be used without spacers. A major drawback of BAI's is the impaction in the upper airway. Stretching the upper airway by a forward leaning body posture with the neck extended ("sniffing position") during inhalation may reduce upper airway impaction and improve pulmonary deposition. Aim of this study was to investigate the reversibility of lung function with different doses salbutamol inhaled with a BAI in the forward leaning posture compared to the standard posture in asthmatic children. 22 clinically stable asthmatic children, 5-14 years old, performed four reversibility measurements. Children inhaled 200 μg or 400 μg salbutamol with a BAI in the standard or in the forward leaning posture with the neck extended in a randomized single-blinded cross-over design. Reversibility of lung function after inhaling salbutamol in the forward leaning posture was not significantly different compared to inhalation in the standard posture. Mean FEV1 reversibility was significantly greater after inhaling 400 μg salbutamol compared to 200 μg salbutamol in the standard posture (9.4% ± 9.5% versus 4.5% ± 7.5%, difference 4.9% (95CI 0.9; 9.0%); p = 0.021). In clinically stable asthmatic children, inhalation of salbutamol with a BAI in a forward leaning posture does not increase reversibility of lung function. Inhalation of 400 μg compared to 200 μg salbutamol with a BAI does improve reversibility. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. In vitro tests for aerosol deposition. III: effect of inhaler insertion angle on aerosol deposition.

    Delvadia, Renish R; Longest, P Worth; Hindle, Michael; Byron, Peter R

    2013-06-01

    Inhaler orientation with respect to a patient's mouth may be an important variable determining the efficiency of aerosol lung delivery. The effect of insertion angle on regional deposition was evaluated for a series of inhalers using concurrent in vitro and computational fluid dynamics (CFD) analysis. Geometrically realistic physical mouth-throat (MT) and upper tracheobronchial (TB) models were constructed to connect different inhalers at a series of insertion angles relative to the horizontal plane of the model. These models were used to assess albuterol sulfate deposition from the Novolizer(®) dry powder inhaler (DPI), Proventil(®) HFA pressurized metered dose inhaler (MDI), and Respimat(®) Soft Mist™ Inhaler (SMI) following the actuation of a single dose. Drug deposition from Novolizer DPI was studied for Salbulin(®) and an experimental "drug only" formulation. Albuterol sulfate was recovered and quantified from the device and the MT and TB regions. Significant differences in MT and total lung dose (TLD) of albuterol sulfate deposition were not observed for Salbulin Novolizer DPI and Respimat SMI inserted at different angles. In contrast, drug-only Novolizer DPI and Proventil HFA MDI showed a significant difference in MT and TLD deposition using different insertion angles. For drug-only Novolizer DPI and Proventil HFA MDI, the lowest and the highest MT depositions were observed at +10° and -20°, respectively; for Respimat SMI and Salbulin Novolizer DPI, these angles were -10° and +10°, and +20° and -20°, respectively. CFD simulations were in agreement with the experimental results and illustrated shifts in local particle deposition associated with changes in insertion angle. The effect of inhaler orientation at the inhaler-mouth interface on MT aerosol deposition appeared to be dependent on velocity, aerosol size, and formulation. These findings not only demonstrate the need for patient education on correct inhaler orientation, but provide important

  9. The importance of continuity in inhaler device choice for asthma and chronic obstructive pulmonary disease.

    Bjermer, Leif

    2014-01-01

    Inhaled therapies are central to the treatment of asthma and chronic obstructive pulmonary disease. Physicians consider many factors when selecting the most appropriate inhaler device, including device efficacy and the cost to the health care system. This review aims to discuss the factors that are important when considering inhaler devices and the importance of continuity in the choice of inhaler device. A large number of factors can contribute to therapeutic outcomes with inhalation devices. The inhalation technique is critical to treatment success and differs substantially between inhaler devices. Misuse of an inhaler is common, and thorough training of patients and physicians is important to ensure correct utilization. Patient satisfaction is an important consideration because it is significantly correlated with compliance and better outcomes. Financial pressures contribute to decision making: although selecting the less expensive inhaler device might reduce direct treatment costs, it can have a large impact on disease control and the patient's well-being. Switching may be associated with a poor inhalation technique, reduced disease control and quality of life, increased use of other treatments and health care resources, and a greater chance of unsuccessful treatment. Nonconsensual switches can result in patient discontent, reduced confidence in the medication, and uncertainty regarding the degree of disease control. It is recommended that patients with stable disease remain on their current device. If a switch is considered, the patient should be consulted and the physician should take into account the patient's preference, their ability to correctly use the device, and the availability of the preferred drug in the preferred device.

  10. Eco-friendly synthesis, in vitro anti-proliferative evaluation, and 3D-QSAR analysis of a novel series of monocationic 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazole mesylates.

    Racané, Livio; Ptiček, Lucija; Sedić, Mirela; Grbčić, Petra; Kraljević Pavelić, Sandra; Bertoša, Branimir; Sović, Irena; Karminski-Zamola, Grace

    2018-04-17

    Herein, we describe the synthesis of twenty-one novel water-soluble monocationic 2-aryl/heteroaryl-substituted 6-(2-imidazolinyl)benzothiazole mesylates 3a-3u and present the results of their anti-proliferative assays. Efficient syntheses were achieved by three complementary simple two-step synthetic protocols based on the condensation reaction of aryl/heteroaryl carbaldehydes or carboxylic acid. We developed an eco-friendly synthetic protocol using glycerol as green solvent, particularly appropriate for the condensation of thermally and acid-sensitive heterocycles such as furan, benzofuran, pyrrole, and indole. Screening of anti-proliferative activity was performed on four human tumour cell lines in vitro including pancreatic cancer (CFPAC-1), metastatic colon cancer (SW620), hepatocellular carcinoma (HepG2), and cervical cancer (HeLa), as well as in normal human fibroblast cell lines. All tested compounds showed strong to moderate anti-proliferative activity on tested cell lines depending on the structure containing aryl/heteroaryl moiety coupled to 6-(2-imidazolinyl)benzothiazole moiety. The most potent cytostatic effects on all tested cell lines with [Formula: see text] values ranging from 0.1 to 3.70 [Formula: see text] were observed for benzothiazoles substituted with naphthalene-2-yl 3c, benzofuran-2-yl 3e, indole-3-yl 3j, indole-2-yl 3k, quinoline-2-yl 3s, and quinoline-3-yl 3t and derivatives substituted with phenyl 3a, naphthalene-1-yl 3b, benzothiazole-2-yl 3g, benzothiazole-6-yl 3h, N-methylindole-3-yl 3l, benzimidazole-2-yl 3n, benzimidazole-5(6)-yl 3o, and quinolone-4-yl 3u with [Formula: see text] values ranging from 1.1 to 29.1 [Formula: see text]. Based on obtained anti-proliferative activities, 3D-QSAR models for five cell lines were derived. Molecular volume, molecular surface, the sum of hydrophobic surface areas, molecular mass, and possibility of making dispersion forces were identified by QSAR analyses as molecular properties that are

  11. Tolerability of inhaled N-chlorotaurine in the pig model

    Scholl-Bürgi Sabine

    2009-07-01

    Full Text Available Abstract Background N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT in the pig model. Methods Anesthetized pigs inhaled test solutions of 1% (55 mM NCT (n = 7, 5% NCT (n = 6, or 1% NCT plus 1% ammonium chloride (NH4Cl (n = 6, and 0.9% saline solution as a control (n = 7, respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed. Results Arterial pressure of oxygen (PaO2 decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH4Cl led to significantly lower PaO2 values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014 with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO2 (p = 0.004. Interestingly, AaDO2 was lowest with 1% NCT, even lower than with saline (p = 0.016. The increase of pulmonary artery pressure (PAP over the observation period was smallest with 1% NCT without difference to controls (p = 0.91, and higher with 5% NCT (p = 0.02, and NCT + NH4Cl (p = 0.05. Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells in vitro was similar to that known from other body cells (0.25–0.5 mM. Conclusion The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of

  12. Biokinetics and internal dosimetry of inhaled metal tritide particles

    Wang, Yansheng

    1998-12-01

    Metal tritides (MT), stable chemical compounds of tritium, are widely used in nuclear engineering facilities. MT particles can be released as aerosols. Inhaling MT particles is a potential occupational radiation hazard. Little information is available on their dissolution behavior, biokinetics, and dosimetry. The objectives of present dissertation are to estimate dissolution rates, to develop biokinetic models, to improve internal dosimetric considerations, and to classify MT materials. This study consisted of three phases: In vitro dissolution in a simulated lung fluid, In vivo rat experiments on retention and clearance, and biokinetic modeling and dosimetric evaluation. There was a supporting study on self- absorption of tritium beta in MT particles. MT materials used in this study were titanium (Ti) and zirconium (Zr) tritides. Results shows considerable self-absorption of beta particles and their energy, even for respirable MT particles smaller than 5 μm. The self-absorption factors should be required for counting MT particle samples and for estimating absorbed dose to tissues. In vitro and in vivo dissolution data indicate that Ti and Zr tritides are poorly soluble materials. Ti tritide belongs to the W class or M type while Zr tritide can be classified as Y class or S type. Due to long retention time of the MT particles, tritium betas directly from the particles contribute over 90% of the absorbed dose to lung. The lung dose contributes most of the effective dose to the whole body. Dissolved tritium including tritiated water (HTO) and organically bound tritium (OBT) has less effect on the lung dose and effective dose. Results on the annual limit on intake (ALI) indicate that the current radiation protection guideline based on HTO is not adequate for inhalation exposure to MT particles and needs to be modified. The biokinetic models developed in this study have predictive powers to estimate the consequences of a human inhalation exposure to MT aerosols. The

  13. Saharan dust levels in Greece and received inhalation doses

    C. Mitsakou

    2008-12-01

    Full Text Available The desert of Sahara is one of the major sources of mineral dust on Earth, producing around 2×108 tons/yr. Under certain weather conditions, dust particles from Saharan desert get transported over the Mediterranean Sea and most of Europe. The limiting values set by the directive EC/30/1999 of European Union can easily be exceeded by the transport of desert dust particles in the south European Region and especially in urban areas, where there is also significant contribution from anthropogenic sources. In this study, the effects of dust transport on air quality in several Greek urban areas are quantified. PM10 concentration values from stationary monitoring stations are compared to dust concentrations for the 4-year period 2003–2006. The dust concentration values in the Greek areas were estimated by the SKIRON modelling system coupled with embedded algorithms describing the dust cycle. The mean annual dust contribution to daily-averaged PM10 concentration values was found to be around or even greater than 10% in the urban areas throughout the years examined. Natural dust transport may contribute by more than 20% to the annual number of exceedances – PM10 values greater than EU limits – depending on the specific monitoring location. In a second stage of the study, the inhaled lung dose received by the residents in various Greek locations is calculated. The particle deposition efficiency of mineral dust at the different parts of the human respiratory tract is determined by applying a lung dosimetry numerical model, which incorporates inhalation dynamics and aerosol physical processes. The inhalation dose from mineral dust particles was greater in the upper respiratory system (extrathoracic region and less significant in the lungs, especially in the sensitive alveolar region. However, in cases of dust episodes, the amounts of mineral dust deposited along the human lung are comparable to those

  14. Pulmonary and Systemic Immune Response to Chronic Lunar Dust Inhalation

    Crucian, Brian; Quiriarte, Heather; Nelman, Mayra; Lam, Chiu-wing; James, John T.; Sams, Clarence

    2014-01-01

    Background: Due to millennia of meteorite impact with virtually no erosive effects, the surface of the Moon is covered by a layer of ultra-fine, reactive Lunar dust. Very little is known regarding the toxicity of Lunar dust on human physiology. Given the size and electrostatic characteristics of Lunar dust, countermeasures to ensure non-exposure of astronauts will be difficult. To ensure astronaut safety during any future prolonged Lunar missions, it is necessary to establish the effect of chronic pulmonary Lunar dust exposure on all physiological systems. Methods: This study assessed the toxicity of airborne lunar dust exposure in rats on pulmonary and system immune system parameters. Rats were exposed to 0, 20.8, or 60.8 mg/m3 of lunar dust (6h/d; 5d/wk) for up to 13 weeks. Sacrifices occurred after exposure durations of 1day, 7 days, 4 weeks and 13 weeks post-exposure, when both blood and lung lavage fluid were collected for analysis. Lavage and blood assays included leukocyte distribution by flow cytometry, electron/fluorescent microscopy, and cytokine concentration. Cytokine production profiles following mitogenic stimulation were performed on whole blood only. Results: Untreated lavage fluid was comprised primarily of pulmonary macrophages. Lunar dust inhalation resulted in an influx of neutrophils and lymphocytes. Although the percentage of lymphocytes increased, the T cell CD4:CD8 ratio was unchanged. Cytokine analysis of the lavage fluid showed increased levels of IL-1b and TNFa. These alterations generally persisted through the 13 week sampling. Blood analysis showed few systemic effects from the lunar dust inhalation. By week 4, the peripheral granulocyte percentage was elevated in the treated rats. Plasma cytokine levels were unchanged in all treated rats compared to controls. Peripheral blood analysis showed an increased granulocyte percentage and altered cytokine production profiles consisting of increased in IL-1b and IL-6, and decreased IL-2

  15. Study on the deposition patterns of aerosol inhalation scintigraphy, 2

    Watanabe, Hiroyuki

    1989-01-01

    The superimposed images obtained by the SPECT of aeresol inhalation scintigraphy and chest CT were applied in 7 cases of diffuse panbronchiolitis. Aerosol deposition patterns were examined, and hot spots were compared with bronchial morphological abnormalities. The results were as follows: 1. Nevertheless, aerosol deposition patterns were characterized by defects of the depositions in the outer zone and hot spots in the inner zone, hot spots distributed from the inner zone to the outer zone. 2. Hot spots and bronchial morphological abnormalities were markedly matched in the inner zone; however, they were mismatched in the outer zone. I concluded that the mechanisms of hot spot formation in the inner zone were different from those in the outer zone. (author)

  16. Regulation of cutaneous allergic reaction by odorant inhalation.

    Hosoi, J; Tsuchiya, T

    2000-03-01

    Olfactory stimuli modulate emotional conditions and the whole body immune system. Effects of odorant inhalation on cutaneous immune reaction were examined. Contact hypersensitivity to 2,4, 6-trinitrochlorobenzene was elicited in C57BL/6 mice. The reaction was suppressed at both the induction and elicitation phases by exposure to an odorant, citralva. Topical application of citralva or lyral/lilial did not affect the reaction. The suppressive effect of citralva was more potent than that of another odorant, lyral/lilial. Citralva decreased the number of epidermal Langerhans cells, whereas lyral/lilial had a weak effect. Citralva but not lyral/lilial induced plasma corticosterone. Glucocorticoid receptor antagonist abrogated the suppressive effect of citralva on contact hypersensitivity. Serum interleukin-12 was downregulated by exposure to citralva or lyral/lilial. These data demonstrate that olfactory stimuli regulate the cutaneous immune system.

  17. Elimination of americium-241 after a case of accidental inhalation

    Edvardsson, K.A.; Lindgren, L.

    1976-01-01

    In handling a 241 Am source one person received an internal contamination of about 140 nCi of americium oxide, which was deposited in the lung region. Elimination of the activity was followed for more than 3 months by external gamma counting and excreta analyses. During the first week after the inhalation about 80% of the total intake was eliminated with an effective half-life of less than 2 days. The remaining activity, deposited in the lung region, was eliminated with an effective half-life of about 17 days. About 15% of the activity eliminated from the lung region from the 10th to the 50th day was eliminated in the faeces. (author)

  18. Disposal of coal and hematite dusts inhaled successively

    Heppleston, A G

    1958-01-01

    Rabbits and rats were exposed in a chamber to coal (20,000 and 10,000 particles/ml) and hematite (20,000 and 37,000 particles/ml) in succession to follow deposition and clearance by color. Exposures were 5 days/wk, 20 hr/day. Generally, there was dust widely but not uniformly distributed in peripheral alveoli, tending to aggregate and clump in more proximal alveoli with time. There was initial nonuniform distribution more uniform with exposure time. Aggregation mostly through phagocyte activities and more evident in rabbits than rats was observed. There was eventual mixing of two dusts inhaled up to 7 months apart. Dust deposited last is cleared first because of less tortuous route.

  19. Dose-effect studies with inhaled plutonium oxide in beagles

    Park, J.F.; Buschbom, R.L.; Case, A.C.

    1976-01-01

    Beagle dogs given single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs dying due to pulmonary fibrosis-induced insufficiency during the first 3 years after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor. Three additional dogs with body burdens of 0.7 to 1.8 μCi died due to pulmonary neoplasia 4-1/2 years after exposure. None of the dogs exposed to 238 Pu have died during the first two postexposure years. After inhalation of 239 PuO 2 or 238 PuO 2 lymphocytopenia was the earliest observed effect, occuring 0.5 to 2 years after deposition of greater than or equal to 80 nCi plutonium in the lungs

  20. NRPB volunteer study: deposition and clearance of inhaled particles

    Etherington, G.; Smith, J.

    1996-01-01

    At the Board Meeting of the National Radiological Protection Board held on 15 February 1996, approval was given for an experimental study of the deposition and clearance of inhaled particles in the human nasal passage. This is the latest in a series of volunteer biokinetic studies that have been conducted at NRPB since its formation. This article explains the purpose of the study, how ethical approval was obtained, how the study will be performed, what volunteers will be asked to do, and what doses they will receive. Doses will of course be carefully controlled, and will be well below the annual limits set for such experiments. The success of the study is of course crucially dependent on recruitment of a sufficient number of volunteers. The aim of this article is to provide information to anyone who might be interested in volunteering. (UK)

  1. Toxicity of inhaled 91YCl3 in beagle dogs

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1980-01-01

    The metabolism, dosimetry and effects of inhaled 91 YCl 3 in beagle dogs are being studied. Forty-two dogs with 91 Y initial body burdens from 14 to 1300 μCi/kg body weight and 12 control dogs are being maintained for lifetime observation. Four additional dogs with a mean initial body burden of 180 μCi/kg body weight were placed in a sacrifice study. Thirty-six of the exposed dogs and 7 of the control dogs have died. Dogs with the highest activity levels died with bone marrow damage and pancytopenia. Three dogs died with nasal cavity carcinomas and three with pulmonary carcinomas and one with hepatic hemangiosarcoma that all appear related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases. Observations are continuing on 10 surviving exposed dogs and six surviving unexposed dogs

  2. Toxicity of inhaled 91YCl3 in Beagle dogs. XV

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.; Jones, R.K.; Kusewitt, D.F.; McClellan, R.O.; Pickrell, J.A.

    1981-01-01

    The metabolism, dosimetry and biological effects of inhaled 91 YCl 3 in Beagle dogs are being studied. Forty-two dogs with initial 91 Y body burdens from 14 to 1300 μCi per kilogram body weight and 12 control dogs are being maintained for lifetime observation. Four additional dogs with a mean initial body burden of 180 μCi per kilogram body weight were placed in a sacrifice study. Forty-three of the exposed dogs and 11 of the control dogs have died. Dogs with the highest initial body burdens died with bone marrow damage and pancytopenia. Three dogs died with nasal cavity carcinomas, three dogs died with pulmonary carcinomas and one dog died with hepatic hemangiosarcoma; these cancers all appeared to be related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases. Observations are continuing on three surviving exposed dogs and one surviving unexposed dog

  3. Brugada syndrome unmasked by accidental inhalation of gasoline vapors.

    Kranjcec, Darko; Bergovec, Mijo; Rougier, Jean-Sébastien; Raguz, Miroslav; Pavlovic, Sonja; Jespersen, Thomas; Castella, Vincent; Keller, Dagmar I; Abriel, Hugues

    2007-10-01

    Loss-of-function mutations in the gene SCN5A can cause Brugada syndrome (BrS), which is an inherited form of idiopathic ventricular fibrillation. We report the case of a 46-year-old patient, with no previous medical history, who had ventricular fibrillation after accidental inhalation of gasoline vapors. His electrocardiogram (ECG) showed a typical type-1 BrS pattern that persisted after the acute event. Genetic investigations allowed the identification of a novel SCN5A mutation leading to a frame-shift and early termination of the channel protein. Biochemical and cellular electrophysiology experiments confirmed the loss-of-function of the mutant allele. The patient was implanted with a cardioverter/defibrillator.

  4. Risks of pneumonia in patients with asthma taking inhaled corticosteroids

    O'Byrne, Paul M; Pedersen, Soren; Carlsson, Lars-Göran

    2011-01-01

    Rationale: Inhaled corticosteroids (ICS) are the mainstay of asthma treatment. Studies in chronic obstructive pulmonary disease reported increased rates of pneumonia with ICS. Concerns exist about an increased pneumonia risk in patients with asthma taking ICS. Objectives: To evaluate the risks...... of pneumonia in patients with asthma taking ICS. Methods: A retrospective analysis evaluated studies of the ICS budesonide in asthma. The primary data set were all double-blind, placebo-controlled trials lasting at least 3 months, involving budesonide (26 trials, n = 9,067 for budesonide; n = 5...... effect of ICS on pneumonia adverse events (AEs) or serious adverse events (SAEs). Measurements and Main Results: In the primary data set, the occurrence of pneumonia AEs was 0.5% (rate 10.0 events/1,000 patient-years [TPY]) for budesonide and 1.2% (19.3 per TPY) for placebo (hazard ratio, 0.52; 95...

  5. Asphyxial suicide by inhalation of chloroform inside a plastic bag.

    Zorro, Andres Rodriguez

    2014-01-01

    Asphyxia suicide by placing a plastic bag over the head in addition with inhalation of gases or use of sedative substances is an unusual method of committing suicide, but frequently referenced by right to die groups in the Internet. This article reports 2 suicides in which chloroform was used to induce unconsciousness and subsequent asphyxia by placing the head in a plastic bag. Case histories of 2 males, ages 23 and 28, are described with special emphasis on characteristics death related to suffocation using plastic bags and chloroform. The final remarkable point in both cases is that the victims previously searched the WEB for instructions of suicide methods. The importance of the phenomenon of misuse of Internet by young people who commit suicide is stressed. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  6. Toxicity of inhaled 91YCl3 in Beagle dogs. XVII

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.; Jones, R.K.; McClellan, R.O.; Pickrell, J.A.

    1983-01-01

    The metabolism, dosimetry, and biological effects of inhaled 91 YCl 3 in Beagle dogs are being studied. Forty-two dogs with initial 91 Y body burdens from 14 to 1300 μCi/kg body weight and 12 control dogs were observed during their life spans. Four additional dogs with a mean initial body burden of 180 μCi 91 Y/kg body weight were placed in a sacrifice study. All 46 of the exposed dogs and all 12 of the control dogs have died. Dogs with the highest initial body burdens died with bone marrow damage and pancytopenia. Three dogs died with nasal cavity carcinomas, three died with pulmonary carcinomas, and one died with hepatic hemangiosarcoma. These cancers all appeared to be related to radiation injury. Control dogs died of miscellaneous neoplastic and chronic diseases

  7. Distribution and retention of inhaled selenium compounds in the rat

    Burkstaller, M.A.; Cuddihy, R.G.

    1978-01-01

    Selenium containing compounds released into the atmosphere during coal combustion are principally of the elemental form or the dioxide. These compounds differ greatly in their chemical properties. Fischer-344 rats were exposed via inhalation to both the dioxide and the red elemental form of selenium. Subsequently, measurements were made of internal absorption, organ distribution and retention, and modes of excretion. A radiotracer, 75 Se, was incorporated into the aerosol to facilitate these measurements. Retention of both aerosols in the total body showed long term components with half lives of 43 and 15 days accounting for 25 to 35% of the initially deposited selenium. Excretion occurred principally by way of urine. For both aerosols, selenium absorbed into the systemic circulation was mainly found in the liver, kidney, blood, gastrointestinal tract and bone

  8. Dose-effect studies with inhaled plutonium oxide in beagles

    Park, J.F.; Buschbom, R.L.; Case, A.C.

    1977-01-01

    Beagle dogs given a single exposure to 239 PuO 2 or 238 PuO 2 aerosols are being observed for life-span dose-effect relationships. The 239 Pu body burden of the nine dogs that died of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 μCi. One of these dogs had a pulmonary tumor. Five additional dogs with body burdens of 0.7 to 1.8 μCi died due to pulmonary neoplasia 3 to 5 yr after exposure. None of the dogs exposed to 238 Pu have died during the first 3 postexposure yr. Lymphocytopenia was the earliest observed effect after inhalation of 239 PuO 2 or 238 PuO 2 , occurring 0.5 to 2 yr after deposition of greater than or equal to 80 nCi plutonium in the lungs

  9. Evaluation of two cases of 244Cm inhalation

    Parkinson, W.W.; Henley, L.C.; Goans, R.E.; Good, W.M.

    1976-01-01

    Chest and systematic burdens have been estimated for two employees who inhaled largely soluble compounds of 244 Cm. Chest burdens by whole body counting were: Case A, 28 nCi; Case B, 34 nCi. The urinary excretion of the employees appeared to conform to a series of exponentials similar to those reported for blood and whole body retention of Am in baboons. Accordingly, retention functions composed of a series of exponentials having 4, 12-17, and 72 day half-times were derived from urinary excretion and used to calculate body burdens, Case A - 7 nCi an Case B - 16 nCi. Cumulative fecal excretion by Case B was some 20 times that by Case A (63 nCi vs. 3.2) probably due to differences in deposition in the respiratory tract. Calculated organ doses for the first year were approximately 20% of recommended maxima

  10. Reporting a sudden death due to accidental gasoline inhalation.

    Martínez, María Antonia; Ballesteros, Salomé; Alcaraz, Rafael

    2012-02-10

    The investigation of uncertain fatalities requires accurate determination of the cause of death, with assessment of all factors that may have contributed to it. Gasoline is a complex and highly variable mixture of aliphatic and aromatic hydrocarbons that can lead to cardiac arrhythmias due to sensitization of the myocardium to catecholamines or acts as a simple asphyxiant if the vapors displace sufficient oxygen from the breathing atmosphere. This work describes a sudden occupational fatality involving gasoline. The importance of this petroleum distillate detection and its quantitative toxicological significance is discussed using a validated analytical method. A 51 year-old Caucasian healthy man without significant medical history was supervising the repairs of the telephone lines in a manhole near to a gas station. He died suddenly after inhaling gasoline vapors from an accidental leak. Extensive blistering and peeling of skin were observed on the skin of the face, neck, anterior chest, upper and lower extremities, and back. The internal examination showed a strong odor of gasoline, specially detected in the respiratory tract. The toxicological screening and quantitation of gasoline was performed by means of gas chromatography with flame ionization detector and confirmation was performed using gas chromatography-mass spectrometry. Disposition of gasoline in different tissues was as follows: heart blood, 35.7 mg/L; urine, not detected; vitreous humor, 1.9 mg/L; liver, 194.7 mg/kg; lung, 147.6 mg/kg; and gastric content, 116,6 mg/L (2.7 mg total). Based upon the toxicological data along with the autopsy findings, the cause of death was determined to be gasoline poisoning and the manner of death was accidental. We would like to alert on the importance of testing for gasoline, and in general for volatile hydrocarbons, in work-related sudden deaths involving inhalation of hydrocarbon vapors and/or exhaust fumes. Copyright © 2011 Elsevier Ireland Ltd. All rights

  11. Unevenness on aerosol inhalation lung images and lung function

    Teshima, Takeo; Isawa, Toyoharu; Hirano, Tomio; Ebina, Akio; Shiraishi, Koichiro; Konno, Kiyoshi

    1985-01-01

    The unevenness or inhomogeneity of aerosol deposition patterns on radioaerosol inhalation lung images has been interpreted rather qualitatively in the clinical practice. We have reported our approach to quantitatively analyze the radioactive count distribution on radioaerosol inhalation lung images in relation to the actual lung function data. We have defined multiple indexes to express the shape and the unevenness of the count distribution of the lung images. To reduce as much as possible the number of indexes to be used in the regression functions, the method of selection of variables was introduced to the multiple regression analysis. Because some variables showed greater coefficients of simple correlation, while others did not, multicollinearity of variables had to be taken into consideration. For this reason, we chose a principal components regression analysis. The multiple regression function for each item of pulmonary function data thus established from analysis of 67 subjects appeared usable as a predictor of the actual lung function: for example, % VC (vital capacity) could be estimated by using four indexes out of the multiple ones with a coefficient of multiple correlation (R) of 0.753, and FEVsub(1.0) % (forced expiratory volume in one second divided by forced expiratory volume), by 7 indexes with R = 0.921. Pulmonary function data regarding lung volumes and lung mechanics were estimated more accurately with greater R's than those for lung diffusion, but even in the latter the prediction was still statistically significant at p less than 0.01. We believe the multiple regression functions thus obtained are useful for estimating not only the overall but also the regional function of the lungs. (author)

  12. Inhalation carcinogenicity study with nickel metal powder in Wistar rats

    Oller, Adriana R.; Kirkpatrick, Daniel T.; Radovsky, Ann; Bates, Hudson K.

    2008-01-01

    Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.1, 0.4, and 1.0 mg Ni/m 3 nickel metal powder (MMAD = 1.8 μm, GSD = 2.4 μm) for 6 h/day, 5 days/week for up to 24 months. A subsequent six-month period without exposures preceded the final euthanasia. High mortality among rats exposed to 1.0 mg Ni/m 3 nickel metal resulted in the earlier termination of exposures in this group. The exposure level of 0.4 mg Ni/m 3 was established as the MTD for the study. Lung alterations associated with nickel metal exposure included alveolar proteinosis, alveolar histiocytosis, chronic inflammation, and bronchiolar-alveolar hyperplasia. No increased incidence of neoplasm of the respiratory tract was observed. Adrenal gland pheochromocytomas (benign and malignant) in males and combined cortical adenomas/carcinomas in females were induced in a dose-dependent manner by the nickel metal exposure. The incidence of pheochromocytomas was statistically increased in the 0.4 mg Ni/m 3 male group. Pheochromocytomas appear to be secondary to the lung toxicity associated with the exposure rather than being related to a direct nickel effect on the adrenal glands. The incidence of cortical tumors among 0.4 mg Ni/m 3 females, although statistically higher compared to the concurrent controls, falls within the historical control range; therefore, in the present study, this tumor is of uncertain relationship to nickel metal exposure. The lack of respiratory tumors in the present animal study is consistent with the findings of the epidemiological studies

  13. Noninvasive 133Xe inhalation method for cerebral blood flow measurement

    Takagi, Shigeharu; Kobatake, Keitaro; Shinohara, Yukito

    1991-01-01

    Recent development of the 133 Xe inhalation technique has made it possible to measure cerebral blood flow (CBF) noninvasively. Recording of the head curves from the frontal and temporal areas during inhalation of 133 Xe, however, is contaminated by the artifact from the air passages. A method based on Fourier transforms was reported to be able to eliminate air passage artifact (APA) effectively. However, it was pointed out that such an algorithm does not give a complete correction if the artifact seen by the head detectors differs in shape from that recorded from the airways at the mouth, which may happen when there is a slow isotope convection in the nasal and sinus cavities. The purpose of this study was to compare the CBF values calculated by the Fourier method with those by the conventional method of Obrist (VM method). Mean hemispheric gray matter flow (F 1 ) calculated by the VM method in 11 subjects, including normal volunteers and patients with various neurological diseases, was 69.2±13.2 mg/100 g brain/ min, whereas F 1 calculated by the Fourier method in the same subjects was 64.4±13.5, indicating that APA can be effectively eliminated by the Fourier method. The F 1 values calculated by the Fourier method from the frontal and temporal regions were relatively high, and closer to the F 1 values calculated by the VM method. The size of the APA was large in these regions. It was concluded that the deformed APA contaminated the results in these regions, and could not be eliminated effectively by the Fourier method. It is suggested that the shape of the head curve and the size of APA should be carefully examined to ensure that CBF data are reliable. (author)

  14. Toxicity of inhaled 238PuO2 II

    Muggenburg, B.A.; Mewhinney, J.A.; Merickel, B.S.; Boecker, B.B.; Hahn, F.F.; Guilmette, R.A.; Mauderly, J.L.; McClellan, R.O.

    1980-01-01

    Studies are in progress to determine dose-response relationships for inhaled 238 PuO 2 . Beagle dogs were given a single, brief, nose-only inhalation exposure to aerosols of monodisperse particles of 238 PuO 2 . Aerosols of two sizes were used, 1.5 μm aerodynamic diameter (AD) and 3.0 μm AD. Dogs were exposed to achieve initial lung burdens of 0.56, 0.28, 0.14, 0.07, 0.03 or 0.01 μCi 238 PuO 2 /kg body weight. Twelve dogs were exposed at each activity level to each aerosol particle size. The local dose around each 3.0 μm AD particle was 10 times higher than the local dose around 1.5 μm AD particles, but the dose averaged over the whole lung was the same at each activity level for both particle sizes. The lung retention of 238 Pu was divided into two phases of clearance. During the first 100 days after exposure, the average retention half-time for 238 Pu in the lung was 310 days. When the solubility changed due to particle breakup, the retention half-time decreased to 180 days during the period from 1OO to 1,500 days after exposure. The first biological effects observed were lymphopenia and neutropenia in peripheral blood. To date, 28 Beagle dogs have died at times from 536 to 1683 days after exposure. Initial lung burdens for the dead dogs ranged from 0.18 to 2.2 μCi 238 Pu/kg body weight. Nine died with radiation pneumonitis and pulmonary fibrosis, 10 died with lung tumors and 19 dogs died with bone tumors. There are 116 exposed and 22 control dogs surviving and under observation. Current patterns of dose versus response are discussed. (author)

  15. Toxicity of inhaled 238PuO2 I

    Diel, J.H.; Mewhinney, J.A.

    1980-01-01

    The deposition, retention, translocation and microscopic distribution of inhaled 238 PuO 2 particles were studied to better define the organs at risk and uniformity of dose and cell types or structures at risk in the lung. Beagle dogs were exposed once by inhalation to an aerosol of 238 PuO 2 with particle aerodynamic diameters of 0.7, 1.4, or 2.7 μm (+-10%). Initial burdens averaged about 700 nCi, a level not expected to induce life-shortening effects in Beagle dogs. Animals were sacrificed at times from 4 hours to 2 years after exposure. Whole body retention of plutonium and its distribution among organs in the sacrificed animals was determined by radiochemical analysis for plutonium content of excreta and tissue samples. The distribution of particles in lung was determined using autoradiographs of lung tissue sections and computer-assisted data collection and analysis. Soon after exposure, PuO 2 was relatively insoluble in lung with individual particles being randomly distributed throughout the lung. A distinct change in the rate of dissolution from lung occurred at about 100 days after exposure resulting in decreased pulmonary retention and increased uptake by liver and skeleton. Particle breakup was observed in autoradiographs for time periods in excess of 128 days after exposure. Broken up particles dissolved rapidly leaving little residue in the lung. The remaining particles were randomly distributed in the lung. These results are discussed in relation to current radiation protection guides for plutonium radionuclides. (author)

  16. Delivery of theophylline as dry powder for inhalation

    Bing Zhu

    2015-12-01

    Full Text Available Theophylline (TP is a very well established orally or intravenously delivered antiasthma drug with many beneficial effects. This study aims to improve asthma treatment by creating a dry powder inhalable (DPI formulation of TP to be delivered directly to the lung, avoiding the side effects associated with conventional oral delivery. The DPI TP formulation was investigated for its physico-chemical characteristics using scanning electron microscopy, laser diffraction, thermal analysis and dynamic vapour sorption. Furthermore, aerosol performance was assessed using the Multi Stage Liquid Impinger (MSLI. In addition, a Calu-3 cell transport assay was conducted in vitro using a modified ACI to study the impact of the DPI formulation on lung epithelial cells. Results showed DPI TP to be physico-chemically stable and of an aerodynamic size suitable for lung delivery. The aerosolisation performance analysis showed the TP DPI formulation to have a fine particle fraction of 29.70 ± 2.59% (P < 0.05 for the TP formulation containing 1.0% (w/w sodium stearate, the most efficient for aerosolisation. Regarding the deposition of TP DPI on Calu-3 cells using the modified ACI, results demonstrated that 56.14 ± 7.62% of the total TP deposited (13.07 ± 1.69 µg was transported across the Calu-3 monolayer over 180 min following deposition, while 37.05 ± 12.62% of the deposited TP was retained in the cells. This could be due to the presence of sodium stearate in the current formulation that increased its lipophilicity. A DPI formulation of TP was developed that was shown to be suitable for inhalation.

  17. The inhalation toxicology of p-aramid fibrils.

    Donaldson, Ken

    2009-01-01

    The pandemic of lung disease caused by asbestos has cast suspicion on any industrial fibrous material that can become airborne in respirable form in workplaces, such that the respirable fibres might be inhaled. Fibre toxicology arose as a sub-specialty of particle toxicology to address the specialised nature of fibre effects and has evolved substantially in the last 25 years. It has yielded valuable information on the dosimetry, structure-activity relationships, and mechanism involved in toxicological effects of a range of fibrous materials, including asbestos, other naturally occurring fibrous materials, and synthetic vitreous fibres. A robust structure/activity paradigm has emerged from this research that highlights fibre length, thinness, and biopersistence as major factors in determining the pathogenicity of a fibre. p-Aramid is a manufactured fibre composed of synthetic polyamide (poly paraphenylene terephthalamide) manufactured on a commercial scale since 1970 by polymerisation and spinning steps. It is used as an advanced composite and in fabrics, body armour, friction materials, etc. Respirable fibrils of p-aramid can be released from the fibres during working and can become airborne. A considerable body of research has been carried out into the hazard posed by inhaled p-aramid fibrils, and this review considers this body of literature and summarises the state-of-the-science in the toxicology of p-aramid fibrils in the light of the existing overarching fibre toxicology paradigm. The peer-reviewed studies demonstrate that p-aramid fibrils can be long and thin but that the fibrils are not biopersistent. Residence in the milieu of the lungs leads to fibre shortening, allowing efficient and complete phagocytosis and effective clearance. Subsequently the p-aramid hazard is low, and this is confirmed in animal studies. The mechanism of shortening of p-aramid fibrils is not well-understood, but may involve the action of macrophages on the fibrils following

  18. Batch crystallization of rifapentine for inhalable tuberculosis medication

    Wijanarko, Anondho; Meivita, Maria Prisca; Hermansyah, Heri; Sahlan, Muhamad; Lakerveld, Richard

    2018-02-01

    In the midst of Tuberculosis (TB) pandemic, a research about new tuberculosis drug that results in more rapid resolution of tubercular infection is important. It will play a crucial role in accelerating the reductions in tuberculosis incidence that is occurring worldwide. The effectiveness of rifapentine has been assessed and it has been proven to be the most effective antibiotics for TB. A frequent administration and dose of rifapentine resulted in more rapid resolution of tubercular infection. However, based on former research, high exposure levels for treatment shortening may be unachievable with oral administration and might instead be achieved by direct aerosol delivery of rifapentine to the pulmonary site of infection. Therefore, with the growing interest in the effectiveness of rifapentine in frequent administration and dose, this research integrates an inhalable form of crystalline rifapentine prepared using a batch process. Moreover, this research investigates the effect of seed loading, supersaturation ratio, and residence time on the characterization of crystalline rifapentine in order to form a crystalline rifapentine in an inhalable size. The research was carried out by using anti-solvent crystallization method with acetone as a solvent and distilled water as an anti-solvent. Based on the assessment of various operating variables, it can be concluded that the optimum result was obtained at the unseeded experiment with supersaturation ratio = 1.26. Unseeded experiments are preferred because the ideal size for therapeutic aerosol was achieved in unseeded experiments. At the request of all authors the above article is being retracted due to publication without knowledge or consent from one of the principal investigators of the research listed on the article, Dr. Richard Lakerveld. This article is retracted from the scientific record with effect from 18 May 2018.

  19. Exposure to acrolein by inhalation causes platelet activation

    Sithu, Srinivas D.; Srivastava, Sanjay; Siddiqui, Maqsood A.; Vladykovskaya, Elena; Riggs, Daniel W.; Conklin, Daniel J.; Haberzettl, Petra; O'Toole, Timothy E.; Bhatnagar, Aruni; D'Souza, Stanley E.

    2010-01-01

    Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6 h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.

  20. Exposure to acrolein by inhalation causes platelet activation

    Sithu, Srinivas D [Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202 (United States); Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); Srivastava, Sanjay; Siddiqui, Maqsood A; Vladykovskaya, Elena; Riggs, Daniel W; Conklin, Daniel J; Haberzettl, Petra; O' Toole, Timothy E; Bhatnagar, Aruni [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40202 (United States); D' Souza, Stanley E., E-mail: sedsou01@louisville.ed [Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202 (United States)

    2010-10-15

    Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5 ppm for 6 h) or sub-chronic (1 ppm, 6 h/day for 4 days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.