Univ., Diss.--München, 1997.

Thesis (doctoral)--Christian-Albrechts-Universität zu Kiel, 2004.

Large quantities of asbestos are used in the building and repairing of ships. Much is used in easily recognisable form and some is incorporated into materials which bear little or no superficial resemblance to the crude fibre at all, but which may still give rise to highly dangerous dust when sawn or otherwise manipulated. The inhalation of this dust over a period of time gives rise to a very disabling and sometimes fatal form or pneumoconiosis known as asbestosis and it is the aim of this article to discuss the prevention of this disease in Dockyard workers .

Recent studies have shown that Ebola virus can persist in wastewater, and the potential for the virus to be aerosolized and pose a risk of inhalation exposure has not been evaluated. We considered this risk for three wastewater systems: toilets, a lab-scale model of an aeration basin, and a lab-scale model of converging sewer pipes. We measured the aerosol size distribution generated by each system, spiked Ebola virus surrogates into each system, and determined the emission rate of viruses into the air. While the number of aerosols released ranged from 105 to 107 per flush from the toilets or per minute from the lab-scale models, the total volume of aerosols generated by these systems was ~10-8 to 10-7 mL per flush or per minute in all cases. The Ebola virus surrogates MS2 and Phi6, spiked into toilets at an initial concentration of 107 PFU mL-1, were not detected in air after flushing. Airborne concentrations of MS2 and Phi6 were ~20 PFU L-1 and ~0.1 PFU L-1, respectively, associated with the aeration basin and sewer models. This corresponds to emission rates of 547 PFU min-1 and 3.8 PFU min-1 of MS2 and Phi6, respectively, for the aeration basin and 79 PFU min-1 and 0.3 PFU min-1 for the sewer model. Since information on the aerosolization of Ebola virus is quite limited, these emission rates can greatly help inform risk assessment of inhalation exposure to Ebola virus. / Master of Science

Exposure to excess manganese via drinking water raises concerns due to potential for adverse neurological impacts, particularly in children. Manganese is ubiquitous in US groundwaters above the SMCL = 0.05 mg/L. Manganese is an essential nutrient, but exposures to elevated manganese have neurotoxic effects. Chapter 2 focuses on human senses\' ability to detect manganese in drinking water. Findings indicate human senses cannot be relied upon to detect excess Mn(II) in drinking water. Mn(IV) is easily visually detected, but cannot be tasted at 10 times the SMCL. Chapter 3 is an assessment the ability of an ultrasonic humidifier to expel drinking water impurities in aerosols. The quality of the water used to charge the humidifier reservoir affects the composition of elements in the aerosols and condensate. Findings indicate condensed humidifier aerosols contain 85% of elements present in the reservoir water for a variety of water types if there is no precipitation. Waters with high concentration of hardness or iron formed precipitates that decreased the concentrations of these metals in the aerosols causing variable results for other elements that were initially present at < 1mg/L in the charge water. This indicates that humidifiers could be a source of inhalation exposure for source water contaminants. / Master of Science

No / Aims To determine the bioavailability of gentamicin to the lung following inhalation from two jet nebulizers. Methods Serial urine samples were obtained from 10 volunteers after a 80 mg dose given orally, nebulized from a Pari LC + (PARI) and MicroNeb III (MN) devices, or after a 40 mg intravenous dose. In vitro aerodynamic characteristics of the nebulized doses were also determined. Results The mean (SD) absolute gentamicin lung bioavailalibility following delivery by PARI and MN devices was 1.4 (0.4) and 1.7 (0.5) %. The mass median aerodynamic diameter (MMAD) of the drug particles from the PARI and MN systems was 8.6 (0.6) and 6.7 (0.5) µm and the corresponding fine particle doses (FPD) were 10.2 (2.8) and 11.7 (1.5) mg. Conclusions The MMAD and FPD data reflect the poor lung deposition of gentamicin identified by urinary excretion.

Current pharmaceutical engineering for the manufacture of binary and combined dry powder inhaler (DPI) dosage forms relies on destructive strategies such as micronisation to generate respirable drug particles. Such processes are inefficient and difficult to control to produce particles of defined quality and functionality for inhaled drug delivery, which can affect drug product performance throughout the shelf-life of the product. Furthermore, owing to current pharmaceutical manufacturing practises of combined inhalation products, these products are subject to greater variability in dose delivery of each active, which may be perpetuated as a function of product storage conditions and limit clinical efficacy of the drug product. Hence, there is a requirement of processes that may enable production of binary and combination DPI products that will allow actives to be delivered more efficiently and independently of dose variations. The aim, therefore, of this study was to develop the solution atomisation and crystallisation by sonication (SAX) process for engineering of single and combination drug particles with suitable physicochemical properties for delivery to the lungs. The SAX process consists of key stages, which include, solution atomisation to produce aerosol droplets, generation of highly supersaturated droplets by evaporation of carrier solvent from aerosol droplet, collection of droplets in a crystallisation vessel containing appropriate non-solvent and the application of ultrasonic waves to the crystallisation vessel. Atomisation of a 1.5% w/v solution of budesonide in dichloromethane resulted in particles with defined surface geometry, which were formulated in binary dry powder inhaler (DPI) formulations and assessed using the next generation impactor.

Made available in DSpace on 2014-06-11T19:27:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-03-18Bitstream added on 2014-06-13T19:55:45Z : No. of bitstreams: 1 araujo_ma_me_araca.pdf: 707645 bytes, checksum: fce723ba876ab19ebb750f9f92ee7b46 (MD5) / Foram analisados os efeitos cardiorrespiratórios e as variações do índice biespectral após a administração da infusão contínua de lidocaína em bezerros anestesiados com isofluorano sob ventilação controlada. Oito bezerros receberam infusão contínua de lidocaína (GL) ou salina 0,9% (GC). Após MPA com xilazina 0,05 mg/kg/IV e indução anestésica com quetamina 2mg/kg associada com midazolam o,1mg/kg, com os bezerros em decúbito lateral procedeu-se a intubação e administrou-se isofluorano 1,3%. Subsequentemente institui-se a VPPI com PPI de 15 cmH2O e fR de 6mpm. Decorridos 40 minutos sob anestesia com isofluorano com ventilação mecânica, aplicou-se lidocaína 2mg/kg e iniciou-se infusão contínua na taxa de 100 µg/kg/minuto (GL). Anotaram-se as variações da FC, PA, fR, SpO2, BIS e TR antes da MPA (MB) e 15 minutos após a MBA (MX) antes da administração da lidocaína (M0) e em intervalos de 20 minutos após o início da infusão dos fármacos (M20, M40, M60 e M80). As demais variáveis foram mensuradas a partir de M0. Após o final da infusão e desconexão, foram avaliados o período de tempo para a adoção de decúbito esternal e posição quadrupedal. Também foi mensurada a concentração sérica da lidocaína. A infusão continua de lidocaína não alterou as variáveis ventilométricas, hemogasométricas, índice biespectral e recuperação, porém diminuiu FC e IC. Conclui-se que apesar de ter causado redução da atividade cardíaca, a infusão contínua de lidocaína pode ser empregada como técnica anestésica em bezerros / Cardiorespiratory effects and bispectral index were analised after continuous rate infusion of lidocaine in calves isoflurane-anesthetized under controlled ventilation. Eight calves received continuous rate infusion of lidocaine (LG) or saline 0.9% (CG). After premedication with xylazine 0.05 mg kg -1 IV and induction of anesthesia with ketamine 2 mg kg -1 associated with the midazolam, 1 mg kg -1 , with the calves in lateral recumbence preceded the intubation and was administered isoflurane 1.3%. IPPV was instituted with PIP of 15 cmH2O and RR of 6 beats min -1 . After 40 minutes with isoflurane anesthesia and mechanical ventilation was applied lidocaine 2 mg kg -1 and continuous rate infusion was started at a rate of 100 mg kg -1 min -1 (LG). Were recorded variations in HR, AP, fR, SPO2, BIS and RT before administration of premedication (MB) and 15 minutes after administration (MX) before administering lidocaine (M0) and every twenty minutes after the start of the infusion of drugs (M20, M40 M60 and M80).The other variables were measured from M0. After the end of infusion and disconnection, were evaluated the time to adopt sternal recumbency and standing position. Also measured the serum concentration of lidocaine. Continuous rate infusion of lidocaine did not change the ventilometry, blood gas, bispectral index and recovery, but decreased HR and CI. We conclude that although there was a reduction in cardiac activity, the continuous infusion of lidocaine may be used as anesthesia in calves

Asthma is a significant lung disease involving chronic inflammation and remodeling of the airways, resulting in reduced quality of life for those who suffer from the condition. Current therapeutic guidelines suggest the use of inhaled corticosteroids for long-term anti-inflammatory relief to manage moderate to severe chronic asthma; however, inhaled corticosteroids fail to provide prophylactic or reversal treatment of damaged airways incurred by chronic asthma as well as exhibiting adverse side effects (skeletal complications, diabetes, and weight gain).Therefore, there is a need for a new type of drug therapy to address these gaps in the treatment of chronic asthma. There is growing interest aimed towards the inhibition of the Janus Kinase and Signal Transducer and Activator of Transcription (JAK-STAT) pathway for the treatment of asthma. Despite the promising opportunity to investigate this new pathway towards this clinical application, no published work is available using an established and characterized JAK 1/3 inhibitor for the treatment of chronic asthma delivered via inhalation. This work investigated tofacitinib citrate, a selective JAK 3 inhibitor, and its potential to be delivered locally to the lungs for the treatment of chronic asthma. Several preformulation studies were conducted to determine the basic physical and chemical properties of the compound and its free base, tofacitinib, for proper inhalational formulation development. The drug was delivered to BALB/c mice challenged with house dust mite (HDM) allergen via nebulization utilizing a nose-only chamber. After a three week dosing schedule, mice treated with tofacitinib citrate exhibited an increase in monocyte cell numbers with a simultaneous decrease in eosinophil cell count, gathered from BAL fluid. Further, the experimental groups treated with tofacitinib citrate had a decrease in total protein concentrations in comparison to the experimental groups that were only challenged with HDM or were both exposed to HDM and vehicle. These findings demonstrated that the proper formulation was developed for nebulized delivery of tofacitinib citrate, and that the compound was capable of reducing total protein concentrations and eosinophil cell recruitment, both recognized as biomarkers for an asthmatic response. Although significant work is still needed to be done, these data hold promise for the potential of a locally delivered JAK 3 inhibitor as a treatment for chronic asthma. Further, the solubility of tofacitinib citrate and five other pharmaceutical salts were determined in HFA 134a, HFA 227, and DFP with varying cosolvent content (0-20% v/v ethanol). The experimental solubilities of the free acid and base compounds were larger than the solubilities of their respective salts in all three systems for tofacitinib, albuterol, and salicylic acid. Warfarin, phenytoin, and ciprofloxacin had similar solubilities with their respective salt forms. Solubilities also increased with increasing cosolvent concentration for all compounds investigated. The model propellant, DFP, provided a slightly stronger correlation of solubility values with HFA 134a in comparison to HFA 227. The observed solubility values were also compared to calculated values obtained from the ideal solubility model, where it was determined that the observed solubility was indeed also dependent on its surrounding solvent interactions and not solely on its ideal solubility (melting point). While some physical changes were observed for the pharmaceutical salts in HFA 134a and 227, more quantitative studies are needed for a larger database of compounds to better understand the factors that contribute to the solubility of pharmaceutical salts (and their correlation to DFP), in HFA-based systems. This information could potentially contribute to a predictive model, saving time and money during the process of pMDI formulation development.

Chapter 1 reviews the literature. It gives a historical overview of hypnosis. It reviews the literature on dental anxiety, including its prevalence and aetiology. It reviews behavioural and cognitive behavioural treatments of dental fear. Inhalation sedation its mechanism of action, effectiveness and draw-backs are discussed. The literature on hypnosis is selectively reviewed, its use in anxiety and dentistry and lastly, the combination of sedation techniques, particularly IHS, is discussed. It is concluded that evidence for the use of hypnosis for the alleviation of dental anxiety needs to be critically addressed. Chapter 2 presents the published protocol of a Cochrane systematic review followed by qualitative results of this review. 11 studies of generally poor quality were included in the review which concludes that there are significant problems with the evidence due to methodological issues, the different outcome measures used and the generally high or unclear risks of bias. There is some evidence that hypnosis may help patients who have a normal range of dental anxiety but who are undergoing a stressful dental procedure. Studies of phobic patients were characterised by high levels of drop-out behaviour and hypnosis could not be shown to be superior to other forms of behavioural treatment. Chapter 3 describes two studies which aimed to develop a Mood Induction Procedure to induce temporary dental anxiety in volunteers. This was used in two later studies. A non-clinical sample was used as a ‘proof of concept’ study was desirable. Study 1tested excerpts of a film, producing only a medium rise in anxiety (ES r = .49). The second study used a shorter, more concentrated film. This produced a large increase in anxiety (ES r=.86). Heart rate was investigated as a possible physiological measure of anxiety, but was not found useful. Chapter 4 describes two randomised controlled studies aiming to investigate whether hypnosis combined with IHS would reduce the anxiety produced by the film more than a control procedure in which IHS was combined with the reading of a story. These studies suggested there may be some effects attributable to hypnosis, but conclusive benefit was not demonstrated. Chapter 5 presents discussion and the overall conclusions of the thesis. Conclusions include the need for further well designed large scale trials involving hypnosis.