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At least 649 records · Page 36Linked to original sources
PubMed2005

EXUBERA: pharmaceutical development of a novel product for pulmonary delivery of insulin.

Development of a product for pulmonary delivery of insulin presented significant technology challenges for this first-in-class pharmaceutical product. These included developing (a) a chemically stabilized protein, (b) a dry powder formulation exhibiting required aerosol physical characteristics, (c) low-dose powder filling and packaging technology, and (d) a mechanical device for powder dispersal and reliable dosing to the patient. The insulin drug is formulated using a novel excipient combination to create a powder with a high glass transition temperature (Tg). The high Tg minimizes insulin mobility (thus reactivity), enabling ambient storage conditions. The formulation composition results in minimal hygroscopicity, where customized packaging produced product ruggedness to humidity. The formulated insulin powder is manufactured by spray-drying. This technology was further engineered to produce the desired reproducible powder characteristics with tight control over particle size and moisture content. A solution step prior to drying assures homogeneity and minimizes dependence on the physical form of the components. Novel low-dose filling and packaging technology reproducibly meters milligram quantities of microfine powder to meet stringent quality requirements for dose control. The technology for accurate, uniform, high-throughput metering of drug powders allows for automation and is scaleable for commercial operations. Finally, the mechanical device design provides powder deagglomeration and dispersion processes in a reusable dry powder inhaler with unique characteristics. The device was designed to rely on patient-generated compressed air as the energy source. A sonic discharge of air through the novel TransJector reproducibly extracts, deagglomerates, and disperses the inhalation powder. A clear holding (spacer-type) chamber allows for patient feedback via dose visualization, and separates powder dispersal from the inspiratory effort. The EXUBERA [Pfizer (New York, NY) and sanofi-aventis (Paris, France)] product provides insulin into the bloodstream with similar reproducibly and effectiveness as subcutaneous injections.

Administration, Inhalation↗
PubMed1994

Behavior of nebulizing solutions and suspensions.

A compressed air source is needed to run a jet nebulizer; its operating pressure affects the aerosol flow through the nebulizer, the quantity of drug and/or solution leaving the nebulizer, and the droplet size. With increasing pressure, the output (gravimetric change during nebulization) will increase and the droplet size decrease. The temperature of the nebulizing solution will decrease by as much as 10 degrees C due to energy loss from evaporation of droplets. Other important considerations in nebulizer therapy are taste, pH and viscosity of the solution. For those drugs which cannot be dissolved, the nebulizing behavior is different. In nebulizing suspensions, the drug particles must be micronized to a mass median diameter of 1-2mum to give optimal output conditions from jet nebulizers with a droplet size of 3mum mass median diameter. The solid drug particles leave the nebulizer through the medium of the droplets, and when a solid drug particle is larger than the droplet it will become trapped in the nebulizer. This has been illustrated in a separate experiment in which 0.5mg/ml budesonide was nebulized from eight different nebulizers. The droplet size as well as the output--calculated from the quantity of drug remaining in the nebulizer after 10 min nebulization--varied with type of nebulizer. A preferable way of determining drug delivery to a patient is to collect the aerosol on a filter during normal breathing and then analyse the drug content on the filter.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1977

A cheap electro-pneumatic high-low bed.

A cheap, simple high-low bed is described for use in wards without a compressed air supply. A main design feature is ease of operation to ensure that the bed is at the correct height for the patient and nurse and to waste as little as possible of the nurse's time.

Beds↗
PubMed2002

A review of assigned protection factors of various types and classes of respiratory protective equipment with reference to their measured breathing resistances.

The British Standards Institution 'Guide to implementing an effective respiratory protective device programme' (BS 4275) lists assigned protection factors (APFs) for various types of respiratory protective equipment (RPE). The APFs were allocated either on the basis of available workplace studies data which met set criteria or on the basis of professional judgement that there is equivalence between its operation and that of a device for which an APF is derived from workplace data. However, in many cases no workplace study information exists to support this professional judgement. As an interim measure, pending information based on workplace measurements, the breathing resistance of a range of tight-fitting RPE from negative pressure filtering devices through to self-contained positive pressure breathing apparatus was measured at various breathing rates. The relative inhalation resistances were then compared on the assumption that similar breathing resistance performance is likely to give similar inward leakage on a facepiece and hence similar protection if all other factors, such as fit, etc., are equal. This work indicates that for most devices the allocation of APFs by analogy to other devices seems to be acceptable. However, there appears to be no justification for the allocation of an APF value of 100 to continuous flow compressed air line breathing apparatus. It is recommended that it should be lowered to 40 until there is valid workplace study data to support the current APF of 100. The work provides an informative insight into the relative performance of devices.

Humans↗
PubMed2003

Exposure assessment to alpha- and beta-pinene, delta(3)-carene and wood dust in industrial production of wood pellets.

The main aim of the study was to measure the exposure to monoterpenes (alpha- and beta-pinene and Delta(3)-carene) and wood dust during industrial production of wood pellets and briquettes. Additional aims were to compare the results from wood dust sampled on a filter with real time measurements using a direct reading instrument and to identify peak exposures to dust. Twenty-four men working at six companies involved in industrial production of wood pellets and briquettes participated in the study. Monoterpenes were measured by diffusive sampling and wood dust was measured as total dust. A data logger (DataRAM) was used for continuous monitoring of dust concentration for 18 of the participants. The sampling time was approximately 8 h. The personal exposure to monoterpenes ranged from 0.64 to 28 mg/m(3) and a statistically significant (Kruskal-Wallis test, P = 0.0002) difference in levels of monoterpenes for workers at different companies was seen. In the companies the personal exposure to wood dust varied between 0.16 and 19 mg/m(3) and for 10 participants the levels exceeded the present Swedish occupational exposure limit (OEL) of 2 mg/m(3). The levels of wood dust during the morning shift were significantly (Mann-Whitney test, P = 0.04) higher compared with the afternoon shift. Continuous registration of dust concentration showed peak values for several working operations, especially cleaning of truck engines with compressed air. For 24 workers in six companies involved in industrial production of wood pellets the personal exposure to monoterpenes was low and to wood dust high compared with the present Swedish OEL and previous studies in Swedish wood industries. Since the DataRAM can identify critical working tasks with high wood dust exposure a reduction in exposure levels could probably be achieved by changes in working routines and by the use of protective equipment.

Alkyl and Aryl Transferases↗
PubMed1986

Rupture of the stomach in a diving accident with attempted resuscitation. A case report.

A compressed air diver suffered pulmonary barotrauma with arterial air embolization; resuscitation was unsuccessful. Attempts at resuscitation included mouth-to-mouth ventilation and cardiac massage. A chest radiograph taken during resuscitation revealed free intraperitoneal air. Postmortem examination showed rupture of the stomach. The two possible aetiological factors--barotrauma of ascent and cardiopulmonary resuscitation--are discussed.

Adult↗
PubMed2004

Abnormal response recovery in the right somatosensory cortex of dyslexic adults.

Somatosensory evoked fields (SEFs) to repetitive tactile stimuli were recorded from eight dyslexic and eight normal-reading adults. Three successive stimuli, produced by diaphragms driven by compressed air, were delivered to thumb, index finger and thumb in sequence, with stimulus-onset asynchronies (SOAs) of 100 and 200 ms in different runs. Both hands were stimulated alternatingly with an intertrain interval of 1 s, and the responses were recorded with a whole-scalp neuromagnetometer. Whereas the primary somatosensory cortex responses to the first stimuli of the trains did not differ between dyslexics and controls, responses to the second stimuli (and the ratios of second to first responses) were significantly smaller in dyslexic than in control subjects in the right hemisphere (differences 41 and 28% for response amplitudes at the 100 and 200 ms SOAs). The results agree with the proposed pansensory nature of temporal processing deficits in dyslexia, specifically demonstrating abnormal response recovery in the right somatosensory cortex.

Adaptation, Physiological↗
PubMed2001

Determination of astragaloside IV in Radix astragali (Astragalus membranaceus var. monghulicus) using high-performance liquid chromatography with evaporative light-scattering detection.

A reverse-phase high-performance liquid chromatographic method is developed for the determination of astragaloside IV, a characteristic constituent in Radix Astragali. Samples are analyzed by means of a reverse-phase column (Zorbax Eclipse XDB C18) using acetonitrile and water under gradient conditions as the mobile phase for 30 min. An evaporative light-scattering detector is used and set at an evaporating temperature of 43 degrees C with a nebulizing gas (compressed air) pressure of 3.4 bar. The detection limit (signal-to-noise ratio > 5) of astragaloside IV is 40 ng on-column.

Astragalus Plant↗
PubMed1999

Fatal case of dichloromethane poisoning.

A 47-year-old man was found dead in a factory where dichloromethane (DCM) tanks were stocked. He was making an inventory of the annual stock of DCM contained in several tanks (5- to 8000-L capacity) by transferring the solvent into an additional tank with the help of compressed air. During this operation, one of the tanks overflowed and the man, who was not wearing any protection, was intoxicated. Autopsy showed digestive, suprarenal, and liver bleeding. Blood was also found in the trachea. DCM was identified by headspace gas chromatography-mass spectrometry (GC-MS). A headspace gas chromatography-flame ionization detection technique (GC-HS-FID) optimized for quantitation in biological fluids, organs and viscera was established at autopsy. The following concentrations of DCM were found: blood (150 mg/L), urine (2.0 mg/L), gastric content (5.6 mg/L), brain (122 mg/kg), fat (99 mg/kg), liver (44 mg/kg), lung (20 mg/kg), and kidney (15 mg/kg). A study of the storage stability of DCM was carried out on these samples. Ethanol production was measured in some organs. The results are discussed in light of the rarity of existing literature.

Fatal Outcome↗
PubMed1999

Mixing of dye in a model scald tank.

A model scald tank was constructed to study the mixing pattern of water in a poultry scalding system. Tank dimensions were approximately 6 m long by 10.5 cm wide with a water depth of 18 cm. Water was vigorously agitated with compressed air delivered through a 1.9-cm polyvinyl chloride pipe on the bottom of the tank. Food coloring was added to the tank at a single point, and water samples were taken at distances of 0, 0.5, 1.0, 1.5, and 2.5 m every 30 s for 10 min, with 0 or 10 L/min water flow through the tank. Dye concentration was determined spectrophotometrically. A chain drive was then installed above the tank with aluminum paddles (area about 25% of tank cross-sectional area) attached to the chain every 15.2 cm to simulate the movement of carcasses through the water at 140 carcasses per minute. Food coloring was added to the tank, and water samples were taken every 15 s for 2.5 min, with 0 or 13.5 L/min water flow through the tank. A computer program based on perfect mixing of water in small slices or cells within the tank was adjusted until predicted dye movement matched sampling data, with correlations of 0.91 or better at all sampling points. For scalder designs with uniform mixing of water, the computer model can predict mixing patterns, including counterflow conditions in a single tank, well enough to yield realistic residence time patterns for bacteria suspended in scald water.

Animals↗
PubMed2005

Reduced extracellular dopamine and increased responsiveness to novelty: neurochemical and behavioral sequelae of intermittent hypoxia.

STUDY OBJECTIVES: Vesicular monoamine transporter and dopamine D1-receptor protein expression are upregulated within the striatum of adults rats exposed to intermittent hypoxic insults as neonates. These observations prompted us to test the hypothesis that intermittent hypoxic insults, occurring during this period of critical brain development, lead to persistent reductions in extracellular levels of dopamine within the striatum. We also tested the hypothesis that post-hypoxic rats exhibit increased novelty-induced behavioral activation and increased basal levels of locomotor activity, two indexes of impaired dopaminergic functioning. STUDY DESIGN: Extracellular levels of dopamine were measured over a 50-hour interval via in-vivo microdialysis. Responsivity to novelty and basal levels of locomotor activity were measured via cubicles equipped with infrared transmitters and photosensors. INTERVENTIONS: Between postnatal days 7 and 11, rat pups were exposed to intermittent hypoxia (20-second bursts of hypoxic gas consisting of 10% oxygen balance nitrogen; 60 events/hour) or compressed air for 6 hours during their major sleep period. On postnatal day 35, locomotor activity was continuously recorded over a 72-hour period. On postnatal day 42, extracellular levels of dopamine were determined in microdialysis samples collected at 30-minute intervals continuously for 50 hours. MEASUREMENTS AND RESULTS: Post-hypoxic rats exhibited heightened behavioral activation when placed into the novel environment of locomotor-recording cubicles. Following 24 hours of adaptation to the cubicles, post-hypoxic rats exhibited locomotor hyperactivity during each dark phase of the circadian cycle, their typical waking period. These same rats also demonstrated reduced levels of extracellular dopamine during both the dark and light phases of the circadian cycle. CONCLUSIONS: We demonstrate increased responsivity to novelty, locomotor hyperactivity, and reduced levels of extracellular dopamine within the striata of juvenile rats exposed to intermittent hypoxic insults between postnatal days 7 and 11. These data, in conjunction with our previous observations, support our hypothesis that intermittent hypoxic insults occurring during a period of critical brain development lead to sequestration of dopamine presynaptically within nigrostriatal axons. We postulate that neonatally occurring hypoxic insults are one potential pathogenic mechanism underlying disorders of minimal brain dysfunction, such as attention-deficit/hyperactivity disorder, characterized by executive dysfunction and hyper responsiveness to novel stimuli, which is responsive to agents promoting enhanced extracellular levels of synaptic dopamine.

Animals↗
PubMed1995

Some effects of d-tubocurarine alone and combined with halothane or isoflurane on neuromuscular transmission.

The mechanisms contributing to the neuromuscular block produced by nondepolarizing muscle relaxants and inhaled anesthetics include: 1) receptor blockade, 2) open or closed ion channel block, 3) decreased transmitter release, and 4) receptor desensitization. In this study we investigated the contributions of receptor and ion channel block. We used the two microelectrode voltage clamp to evaluate miniature end-plate currents (MEPCs) for amplitude and time constant of decay (tau) before and after the application of 1) d-Tubocurarine (DTC) (10(-7)-10(-6) M) alone, and then 2) the same concentration of DTC plus 0.5% or 1.0% halothane or isoflurane delivered by passing compressed air through a flow and temperature compensated vaporizer. The electrodes were maintained in the same cell for the entire experiment. DTC alone decreased MEPC amplitude to 91.3% +/- 4.5% and 65.1% +/- 5.6% of control at 10(-7) and 10(-6) M, respectively. MEPC amplitude with 10(-6) M DTC decreased further to 52.4% +/- 7.6% and 37.4% +/- 7.0% of control after the addition of 0.5% and 1.0% halothane, respectively. After the application of DTC 10(-7) M tau was 94.7% +/- 3.1% of control and decreased to 73.7% +/- 7.1% of control with 10(-6) M DTC. After the application of DTC 10(-6) M the addition of 0.5% and 1% halothane decreased tau to 52.4% +/- 7.6% and 30.0% +/- 5.9% of control. Isoflurane produced similar changes. This study provides evidence that at least some of the augmentation of nondepolarizing relaxants by inhaled anesthetics can be explained by the additive effect of nondepolarizing muscle relaxants and inhaled anesthetics on MEPC amplitude and tau.

Anesthetics, Inhalation↗
PubMed1977

Contamination of medical gas and water pipelines in a new hospital building.

Medical gases and water were sampled and tested for purity prior to the opening of a 176-bed addition to a 450-bed general hospital. Contamination was found. In delivered oxygen, compressed air, and nitrous oxide, this consisted of a volatile hydrocarbon at an initial concentration of 10 parts per million and a dust of fine gray particulate matter. In water from new taps bacterial contamination with as many 400,000 organisms per 100 ml was present. All these contaminants were considered potential hazards to patient safety. Studies were done to help delineate the nature and origin of these contaminants. Each contaminant was eventually largely eliminated by purging the respective pipeline systems with continuous flows. Planners, builders, and responsible medical personnel must be aware of the potential for such hazards in a new hospital building.

Central Supply, Hospital↗
PubMed1979

Carcinogenicity of halothane in Swiss/ICR mice.

A simplified in-vivo bioassay system was used to test the carcinogenic potential of halothane in Swiss/ICR mice. Halothane was tested only at its maximum tolerated dose, and histologic examination was performed only on tumor masses and other grossly abnormal tissues found at necropsy. Two groups, each of 15 timed pregnant mice, were exposed to either halothane, 500 ppm (0.05 per cent), or compressed air for two hours on days 10--19 of pregnancy. Five days after birth the offspring were similarly exposed, three times weekly, for 78 weeks. After a ten-week, no-treatment, observation period, all remaining mice were examined by necropsy. Mice dying or killed in extremis before final sacrifice at 88 weeks of age also underwent complete gross necropsy unless extensive cannibalism or autolysis precluded examination. The incidences of malignant tumors, hepatomas or modular hyperplasias, and benign tumors in halothane-treated mice were 7, 6, and 20 per cent, respectively; there were similar incidences of these lesions in control animals. It is concluded that under the conditions of this experiment, lifetime administration of halothane at its maximum tolerated dose is not associated with an increased incidence of neoplasia in Swiss/ICR mice.

Adenoma↗
PubMed1982

Carcinogen bioassay of enflurane in mice.

A carcinogen bioassay of enflurane was performed in Swiss/ICR mice. Two groups of weanling mice, each of 125 males and 125 females, were exposed to eigher a maximum tolerated dose of enflurane, 3000 ppm (0.3 per cent v/v) or compressed air for 4 hs per day, 5 days per week. After 52 weeks exposure, 25 males and 25 females from each group were killed. After 78 weeks exposure, a 4-week period without treatment was allowed before the remaining mice were killed. Mice killed at the scheduled periods and those killed or dying at other times throughout the study, underwent extensive gross and histologic, examinations unless autolysis or cannibalism precluded examination. After 78 weeks exposure, male mice in the enflurane-treated group had a 36 per cent incidence of liver tumors compared with 24 per cent in the control group; however, the difference was no statistically significant. The incidence of lung tumors was about 20 per cent in all groups. Other neoplastic lesions occurred in small numbers and were unrelated to treatment. It was concluded that under the conditions of the present experiment, chronic administration of enflurane at its maximum tolerated dose did not lead to an increased incidence of neoplasia in Swiss/ICR mice.

Adenoma↗
PubMedDate not supplied

Correlation of gross and microscopic appearance of skin buttons in total artificial heart animals.

Pneumatic artificial hearts are powered by compressed air that is delivered through percutaneous tubes. A stress relief device, termed a skin button, surrounds these tubes as they exit from the recipient's tissues. The skin button is designed to protect the tissues from damage and provide a secure material-tissue interface. Prevention of superficial and invasive infection is the primary goal of the skin button. Eight calves were studied prospectively to identify gross or microscopic infection with the skin button. All animals who survived more than sixty days (62-136) had both gross and microscopic evidence of infection. All animals surviving less than 60 days (13-43) had no gross evidence of infection but one had subcutaneous microscopic abscess formation. No animal died secondary to a skin button infection. Skin buttons cannot prevent infection but they can contain the pathologic process in the superficial tissues with no evidence of systemic effects.

Animals↗
PubMed1992

Measurement of SO2 effects on the 218Po ion mobility spectrum by alpha-track detection.

A number of investigators have reported the formation of radiolytic ultrafine particles produced by the interaction of ionizing radiation with atmospheric trace gases. Previous studies have suggested that a very high localized concentration of the OH radical produced by the radiolysis of water can react with atmospheric trace gas, like SO2, to produce lower vapor pressure compounds that can then nucleate. To determine trace-gas dependence of the active, positively charged, first decay product of radon, the mobility spectrum of the decay products in the range of 0.06-3.0 cm2 V-1s-1 was measured in a flow-through radon chamber using a specially designed mobility spectrometer. Measurements were taken for different relative humidities and concentrations of SO2 in purified laboratory compressed air. The resultant mobility spectra were compared with radiolytic ultrafine particle activity distribution data. In the case of low humidities, the reduction of available OH concentration and hence neutralization rate led to the increasing intensity of the shoulder around 1.35 cm2 V-1s-1 with increasing SO2, suggesting SO2 clustering around the PoOx+ ion. For high humidity conditions (5 ppm SO2, 30% RH), there was clear droplet formation, H2SO4, clustering around the ion, and also an increase in the background level between the high mobility peak and droplet peak.

Bismuth↗
PubMed2000

Effects of blast exposure on exercise performance in sheep.

BACKGROUND: The effects of blast on maximal exercise performance were investigated in sheep that were trained to perform maximal exercise. METHODS AND RESULTS: Sheep were fully instrumented for determination of pulmonary and systemic hemodynamics. Blast exposure was administered by using a compressed air driven shock tube that was positioned to primarily produce cardiopulmonary injury. Four levels of exposure were used that were known to produce sublethal injury ranging from little or no grossly observable cardiopulmonary injury (level 1) to confluent ecchymosis of the heart, lung, or both (level 4). We evaluated maximal exercise performance 1 hour after exposure to level 1, level 2, and level 3 and 24 hours after level 3 and level 4. VO2max was not significantly decreased 1 hour after exposure to level 1 but was decreased after exposure to level 2 (29.9%) and level 3 (49.3%). Significant improvement in exercise performance was observed in 24 hours, as VO2max was not significantly decreased 24 hour after level 3. VO2max was decreased 24 hour after level 4 injury (30.8%). CONCLUSION: Cardiovascular data collected during exercise suggested that acute cardiopulmonary injury is responsible for the exercise performance decrement observed 1 hour after exposure and that significant recovery of function is observed 24 hours after blast injury.

Animals↗