Risk of bleeding in patients undergoing pulmonary procedures on antiplatelet or anticoagulants: A systematic review.

As many as 25% of all patients undergoing invasive pulmonary procedures are receiving at least one antiplatelet or anticoagulant agent. For those undergoing elective procedures, the decision-making process is uncomplicated and the procedure may be postponed until the antiplatelet or anticoagulant agent may be safely held. However, many invasive pulmonary procedures are semi-elective or emergent in nature in which case a risk-benefit calculation and discussion occur between the provider and patient or surrogate decision-maker. Therefore, it is critical for providers to have an awareness of the risk of bleeding complications with different pulmonary procedures on various antiplatelet and anticoagulant agents. This systematic review summarizes the bleeding complications associated with different pulmonary procedures in patients on various antiplatelet or anticoagulant agents in the literature and reveals a paucity of high-quality evidence across a wide spectrum of pulmonary procedures and antiplatelet or anticoagulant agents. The results of this review can help inform providers of the bleeding risk in these patients to aid in the shared decision-making process and risk vs benefit discussion.

The biomechanical effect of radial shortening on the radiocapitellar articulation.

Repeated trauma to the radial head may be one of the causative factors in the genesis of osteochondritis dissecans of the capitellum. We measured the force, contact area and pressure across the radiocapitellar articulation of the elbow before and after radial shortening osteotomy in five fresh-frozen cadaver upper limbs with loads of 45, 90 and 135 N, respectively. Measurements were made on pressure-sensitive film placed in the radiocapitellar articulation with the forearm in the supinated, neutral and pronated positions before and after radial shortening. Radial shortening significantly reduced the mean force and contact area across the radiocapitellar articulation in all positions of the forearm.

A revised model for electron dosimetry in the human small intestine.

In this study, the absorbed dose was calculated to the small intestine (SI) wall of an adult human from electrons in its lumen contents. The effects on dose due to variations in the lumen radius and wall-thickness also were studied. The SI model was based on values gleaned from anatomic and histologic reviews of the adult human SI. Histologic and radiological analyses of the SI suggested the microscopic intricacy of this walled organ could be avoided for dosimetric purposes and a set of concentric cylinders could be used to model the SI. The model was input into the Monte Carlo N-Particle (MCNP) version 4A computational package, which was used to simulate energy deposition in the SI by electrons of fifty discrete energies ranging 10-500 keV. The source electrons as well as all resulting particles, such as knock-on electrons, bremsstrahlung, and electrons created from bremsstrahlung interactions, were transported until the particle energies fell below the 1 keV low-energy cutoff. Detailed physics treatments for secondary photons were made. With a reasonable number of histories, appropriate variance reduction techniques were used to improve the precision of the Monte Carlo calculations. The model used very small tally regions, which ranged in thickness from 0.5 microm to 200 microm depending on the electron energy studied and tally location in the wall. Relative errors associated with these calculations were maintained at less than 5%. The large number of tally results across the wall for each of the energies studied enabled the construction of the energy-specific depth dose curves in the wall. Each of these curves was consistent with the anticipated energy deposition pattern. These curves showed that only a small fraction of the energy absorbed at the contents-mucus interface reaches the stem cell layers because the cells are located deep in the mucosa. This fraction was found to vary from 1.66 x 10(-6) to 1.21 x 10(-1) over the energy range 10-500 keV. These results demonstrated the interface dose, which has been routinely reported as the "wall" dose, is a significant overestimate of the actual dose to the stem cells. The dose uncertainties associated with variations of the critical cell depth were shown to be very high for electrons whose CSDA ranges in the soft tissue exceeded the depth of the critical cells. This study showed that the uncertainty in the wall-thickness had no effect on depth doses while variation in the lumen radius significantly changes depth doses. The results suggest that these changes could be approximated by the inverse square of the lumen radius.

Radiological assessment of petroleum pipe scale from pipe-rattling operations.

Petroleum pipe scale, consisting of concentrated inorganic solids such as barium sulfate, can deposit on the inside of down-hole pipes during the normal course of oil field pumping operations. A portion of this scale has been shown to contain naturally occurring radioactive materials (NORM), predominantly compounds of radium. When these pipes are removed from the well, there is a potential for radiation doses to the oil field workers handling the pipes, especially as the pipes are cleaned for reuse. A thorough sampling and measurement protocol was applied under a variety of weather conditions in an outdoor laboratory to obtain an accurate indication of the radiological and aerodynamic characteristics of scale release and dust dispersion during petroleum pipe scale removal from out-of-service pipes with a restored, historically relevant outdoor pipe-cleaning machine. Exposure rate data were also obtained for both the pre-cleaned pipes, and the general area inhabited by workers during the descaling operation. Four radiation exposure pathways were investigated: inhalation of pipe scale dust generated during pipe rattling, incidental ingestion of the pipe scale dust, external exposure from uncleaned pipes, and external exposure from pipe scale dispersed on the ground. Pipes from three oil fields were rattled to collect as much industry-representative data as possible. The Ra specific activity of the pipe scale ranged from 33.6 +/- 0.4 to 65.5 +/- 0.7 Bq g, depending on the formation. A median atmospheric dust loading of 0.13 mg m was measured in the operator breathing zone. The respirable fraction was observed to be about 42% to 46%. Based on cleaning 20 pipes per day,250 d per year on average, annual committed effective doses for the operator and helper ranged from 0.11 mSv (11 mrem) to 0.45 mSv(45 mrem) for inhalation and from 19 microSv (1.9 mrem) to 97 microSv (9.7 mrem) for incidental ingestion. Worker annual external dose from the pipe racks ranged from 0 to 0.28 mSv (28 mrem). In the deposition experiment, more than 99% by weight of the deposited scale fell within 2 m of the machine centerline, the vast majority of which was in the downwind direction. The dose from this deposited material dominated the worker dose estimates. The annual external dose from dispersed material was estimated to be 2.8 mSv (280 mrem) for the operator and 4.1 mSv (410 mrem) for the helper.

Effects of SR141716A, a central cannabinoid receptor antagonist, on food-maintained responding.

Previous reports have indicated that administration of the central cannabinoid receptor (CB(1)) antagonist SR141716A decreases intake of highly palatable food and drink. Disruption of normal food intake has been reported only at high doses known to disrupt spontaneous behaviors. The present study was designed to determine if rates of responding for normal food were sensitive to the effects of cannabinoid receptor blockade. Adult, male Sprague-Dawley rats were trained to lever press for normal food pellets under a fixed-ratio 15 (FR 15) schedule of reinforcement. SR141716A (0.3-3.0 mg/kg) produced dose-dependent reductions in response rate. WIN 55,212-2 (0. 3 mg/kg), a high efficacy cannabinoid agonist, given as a pre-treatment to SR141716A, significantly attenuated the rate-suppressing effects of SR141716A, suggesting a principal role of CB(1) receptors in mediating these behavioral effects. These data indicate that high palatability is not necessary to observe an anorectic effect of SR141716A.

A dosimetric model for inhaled radioactive gases.

Mathematical simulation models have been used to study transport of insoluble and nonreactive gases for more than twenty years. However, gas and vapor transport and uptake still are not well understood, and a mathematical model for slightly soluble and nonreactive gas transport and uptake still has not been developed. This paper describes the development of a mathematical model of diffusion, convection, lateral transport into the airway wall, and alveolar absorption for inhaled radioactive gases in human conductive and respiratory airways. The model is based on a single-path trumpet-bell model. Sensitivity studies were conducted to ascertain the influence on the final model of the functional residual capacity, the tidal volume and diffusivity and solubility. Results obtained with this model are presented for HT gas exposure and are compared with other findings. In general, the results obtained in this research are in good agreement with other mean experimental results.

Identification and characterization of a putative active site for peptide methionine sulfoxide reductase (MsrA) and its substrate stereospecificity.

Peptide methionine sulfoxide reductases (MsrA) from many different organisms share a consensus amino acid sequence (GCFWG) that could play an important role in their active site. Site-directed single substitution of each of these amino acids except glycines in the yeast MsrA resulted in total loss of enzyme activity. Nevertheless, all the recombinant MsrA mutants and native proteins had a very similar circular dichroism spectrum. The demonstration that either treatment with iodoacetamide or replacement of the motif cysteine with serine leads to inactivation of the enzyme underscores the singular importance of cysteine residues in the activity of MsrA. The recombinant yeast MsrA was used for general characterization of the enzyme. Its K(m) value was similar to the bovine MsrA and appreciably lower than the K(m) of the bacterial enzyme. Also, it was shown that the enzymatic activity increased dramatically with increasing ionic strength. The recombinant yeast MsrA activity and the reduction activity of free methionine sulfoxide(s) were stereoselective toward the L-methionine S-sulfoxide and S-methyl p-tolyl sulfoxide. It was established that a methionine auxotroph yeast strain could grow on either form of L-methionine sulfoxide.

Absorbed dose from traversing spherically symmetric, Gaussian radioactive clouds.

If a large radioactive cloud is produced, sampling may require that an airplane traverse the cloud. A method to predict the absorbed dose to the aircrew from penetrating the radioactive cloud is needed. Dose rates throughout spherically symmetric Gaussian clouds of various sizes, and the absorbed doses from traversing the clouds, were calculated. Cloud size is a dominant parameter causing dose to vary by orders of magnitude for a given dose rate measured at some distance. A method to determine cloud size, based on dose rate readings at two or more distances from the cloud center, was developed. This method, however, failed to resolve the smallest cloud sizes from measurements made at 1,000 m to 2,000 m from the cloud center.

MIRD Pamphlet No. 15: Radionuclide S values in a revised dosimetric model of the adult head and brain. Medical Internal Radiation Dose.

UNLABELLED: Current dosimetric models of the brain and head lack the anatomic detail needed to provide the physical data necessary for suborgan brain dosimetry. During the last decade, several new radiopharmaceuticals have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head for use in estimating regional absorbed dose within the brain and its adjacent structures. METHODS: A new brain model has been developed that includes eight subregions: the caudate nuclei, the cerebellum, the cerebral cortex, the lateral ventricles, the lentiform nuclei, the thalami, the third ventricle and the white matter. This brain model is incorporated within a total revision of the head model presented in MIRD Pamphlet No. 5 Revised. Modifications include the addition of the eyes, the teeth, the mandible, an upper facial region, a neck region and the cerebrospinal fluid within both the cranial and spinal regions. RESULTS: Absorbed fractions of energy for photon and electron sources located in 14 source regions within the new model were calculated using the EGS4 Monte Carlo radiation transport code for particles in the energy range 10 keV-4 MeV. These absorbed fractions were then used along with radionuclide decay data to generate S values for 24 radionuclides that are used in clinical or investigational studies of the brain, 12 radionuclides that localize within the cranium and spinal skeleton and 12 radionuclides that selectively localize in the thyroid gland. CONCLUSION: A substantial revision to the dosimetric model of the adult head and brain originally published in MIRD Pamphlet No. 5 Revised is presented. This revision supports suborgan brain dosimetry for a variety of radiopharmaceuticals used in neuroimaging. Dose calculations for the neuroimaging agent 1231-tropane provide an example of the new model and yield mean brain doses that are consistent with published values. However, the absorbed dose to subregions within the brain such as the caudate and lentiform nuclei may exceed the average brain dose by a factor of up to 5.

Calculation of effective doses for broad parallel photon beams.

Values of effective dose (E) were calculated for the entire range of incident directions of broad parallel photon beams for selected photon energies using the Monte Carlo N-Particle (MCNP) transport code with a hermaphroditic phantom. The calculated results are presented in terms of conversion coefficients transforming air kerma to effective dose. This study also compared the numerical values of E and H(E) over the entire range of incident beam directions. E was always less than H(E) considering all beam directions and photon energies, but the differences were not significant except when a photon beam approaches some specific directions (overhead and underfoot). This result suggests that the current H(E) values can be directly interpreted as E or, at least, as a conservative value of E without knowing the details of irradiation geometries. Finally, based on the distributions of H(E) and E over the beam directions, this study proposes ideal angular response factors for personal dosimeters that can be used to improve the angular response properties of personal dosimeters for off-normal incident photons.

Overexpression of peptide-methionine sulfoxide reductase in Saccharomyces cerevisiae and human T cells provides them with high resistance to oxidative stress.

The yeast peptide-methionine sulfoxide reductase (MsrA) was overexpressed in a Saccharomyces cerevisiae null mutant of msrA by using a high-copy plasmid harboring the msrA gene and its promoter. The resulting strain had about 25-fold higher MsrA activity than its parent strain. When exposed to either hydrogen peroxide, paraquat, or 2,2'-azobis-(2-amidinopropane) dihydrochloride treatment, the MsrA overexpressed strain grew better, had lower free and protein-bound methionine sulfoxide and had a better survival rate under these conditions than did the msrA mutant and its parent strain. Substitution of methionine with methionine sulfoxide in a medium lacking hydrogen peroxide had little effect on the growth pattern, which suggests that the oxidation of free methionine in the growth medium was not the main cause of growth inhibition of the msrA mutant. Ultraviolet A radiation did not result in obvious differences in survival rates among the three strains. An enhanced resistance to hydrogen peroxide treatment was shown in human T lymphocyte cells (Molt-4) that were stably transfected with the bovine msrA and exposed to hydrogen peroxide. The survival rate of the transfected strain was much better than its parent strain when grown in the presence of hydrogen peroxide. These results support the proposition that the msrA gene is involved in the resistance of yeast and mammalian cells to oxidative stress.

Effective dose equivalent and effective dose for photon exposures from point and disk sources on the floor.

A complete set of H(E) and E values were calculated for photon exposures from point and disk sources on the floor using the MCNP code and a "hermaphroditic" phantom. It was found that a male can receive a higher H(E) or health risks than a female by a factor of two from an identical point source on the floor when source distance is less than 50 cm. Conversely, if the source distance becomes larger than 100 cm, the female receives H(E) higher than the male by up to 40%. For identical sources, both the male and female experience significantly higher H(E) from front-located sources than from back- or side-located sources. For a 100-cm source distance, male H(E) from a front-located source is greater than that from a side-located source by factors of 4, 3, and 2 for 0.08, 03, and 1.0 MeV photons, respectively. In the female cases, the differences are somewhat smaller but still differ by factors of 3, 2, and 1.7. It was also found that both the highest male and female H(E) values occur when a source is within 40-60 cm in front of the phantom. The maximum male H(E) is 1.8 x 10(-18), 6.6 x 10(-18), and 2.1 x 10(-17) Sv per photon emission for 0.08, 03, and 1.0 MeV photons, respectively. For females, these maximum values are slightly smaller, 1.4 x 10(-18), 5.3 x 10(-18), and 1.9 x 10(-17) Sv/photon, respectively. Tissue kerma free-in-air at 100 cm above a disk source (Ktissue) was found to greatly overestimate H(E) if the source radius is less than 200 cm. For radii larger than 200 cm, the Ktissue gives a relatively better estimate of H(E), overestimating by not more than 100%. The point source H(E) values were directly integrated to estimate H(E) for simple non-self-shielding sources such as disk, circle, and line sources. This simple approach was found to overestimate H(E) by less than 10% for these irradiation geometries. Finally, the comparison of H(E) and E showed that for most cases these values are almost identical. For point sources, when source distance is larger than 50 cm, the difference between H(E) and E was always less than 23% over photon energies between 0.08 and 1.0 MeV. For disk sources of radius larger than 50 cm, the difference was even smaller (<12%).

The yeast peptide-methionine sulfoxide reductase functions as an antioxidant in vivo.

A gene homologous to methionine sulfoxide reductase (msrA) was identified as the predicted ORF (cosmid 9379) in chromosome V of Saccharomyces cerevisiae encoding a protein of 184 amino acids. The corresponding protein has been expressed in Escherichia coli and purified to homogeneity. The recombinant yeast MsrA possessed the same substrate specificity as the other known MsrA enzymes from mammalian and bacterial cells. Interruption of the yeast gene resulted in a null mutant, DeltamsrA::URA3 strain, which totally lost its cellular MsrA activity and was shown to be more sensitive to oxidative stress in comparison to its wild-type parent strain. Furthermore, high levels of free and protein-bound methionine sulfoxide were detected in extracts of msrA mutant cells relative to their wild-type parent cells, under various oxidative stresses. These findings show that MsrA is responsible for the reduction of methionine sulfoxide in vivo as well as in vitro in eukaryotic cells. Also, the results support the proposition that MsrA possess an antioxidant function. The ability of MsrA to repair oxidative damage in vivo may be of singular importance if methionine residues serve as antioxidants.

Calculation of the dose distribution in water from 71Ge K-shell x-rays.

The dose distribution in water from 71Ge K-shell x-rays (Eave = 9.44 keV) was calculated for various source configurations using both analytic and EGS4 Monte Carlo calculations. The point source kernel and the buildup factor are presented. The buildup factor for a point source in water has been found to increase up to about 1.1 as radial distance approaches 1 cm. Comparison between 71Ge and 90Sr/Y shows a similarity between their relative dose distribution in water. The dose distribution from a disc source was calculated using the EGS4 code and compared with the results from analytic calculation. Excellent agreement was observed, confirming the validity of analytic calculations. The dose rate at 0.01 cm from a 71Ge disc source was calculated to be about 1.3 x 10(-5) Gy MBq-1 s-1. Based on the results from this study, 71Ge activity of the order of 3.7 x 10(10) Bq (approximately 1 Ci) might be necessary to obtain dose rates typical of 90Sr/Y ophthalmic applicators. The possibility of using 71Ge as a source of radioactive stents was also investigated. A 71Ge stent was modelled as a cylindrical shell source and the dose rates were determined by Monte Carlo calculations. Some calculated results are compared with published values for a 32P-coated stent. The dose rate at 0.01 cm from a 71Ge stent has been calculated to be about 6.5 x 10(-3) Gy MBq-1 h-1, which is much lower than the reported dose rate at the same distance from a 32P-coated stent. However, an initial source activity of the order of 3.7 x 10(7) Bq (approximately 1 mCi) would easily result in a typical target dose (approximately 24 Gy) needed for intravascular stent applications. In conclusion, 71Ge sources could be used as alternatives to beta sources and, unlike high-energy (approximately MeV) beta sources, may provide easily predictable dose distributions in heterogeneous media and low dose rates, which might be beneficial for some clinical applications.

Calculation of absorbed energy in the gastrointestinal tract.

One goal of this research was to reproduce the photon specific absorbed fraction calculations of Cristy and Eckerman using their gastrointestinal (GI) tract model. A second goal was to calculate photon specific absorbed fraction values for their GI tract model using electron tracking techniques. A final goal was to calculate electron absorbed fraction values for their GI tract model. This paper summarizes the work performed using the currently accepted model of the GI tract provided by Cristy and Eckerman. Their model was coded into the Electron Gamma Shower 4 (EGS4) computational package for calculation of photon specific absorbed fraction values. To benchmark the initial code, the EGS4 program was run so that all secondary particles deposited their energy at the site of the primary photon interaction (i.e., without electron tracking). The results obtained from these preliminary calculations were compared to those provided by Cristy and Eckerman to verify and benchmark the program. Next, specific absorbed fraction values were calculated for twelve discrete photon energies using the electron tracking capabilities of EGS4. These photon specific absorbed fraction values were compared to those calculated without electron tracking. Finally, absorbed fraction values were calculated for twelve discrete electron energies. The electron absorbed fraction values were compared to those calculated without electron tracking. Finally, absorbed fraction values were calculated for twelve discrete electron energies. The electron absorbed fraction values were compared to the ICRP "one-half assumption" for electron energy deposition in the wall of the GI tract.

A revised model for the calculation of absorbed energy in the gastrointestinal tract.

The goal of this research was to develop a more complete gastrointestinal (GI) tract model for use in internal dose assessment. This paper summarizes the development of a revised mathematical model of the GI tract. The current GI tract model assumes the wall can be represented as a single soft tissue layer without regard to the radiosensitivity of the cells. The goal of the GI tract revision was to develop geometric regions that separate the radiosensitive cells from the less radiosensitive cells. Once the model was revised, it was coded into the Electron Gamma Shower 4 (EGS4) computational package for calculation of photon and electron absorbed fraction values. Photon absorbed fraction values were calculated for twelve discrete energies. For the photon absorbed fraction calculations, the EGS4 program was run so that secondary particles created in photon interactions were followed using the electron tracking capabilities of EGS4. The results of the photon absorbed fraction calculations provided better estimates of the energy deposited in the radiosensitive cells when the target organ was the source. In cases where the target organ was not the source, the photon absorbed fraction values did not provide better estimates than those obtained using the current GI tract model. An increase in the number of photon histories should provide better estimates of the photon absorbed fraction for these cases. Electron absorbed fraction values also were calculated for twelve discrete electron energies. The results of these calculations provided the expected pattern of energy deposition and better estimates than those currently available. The annual limit on intake was recalculated for a single radionuclide to demonstrate the affect of these improved absorbed fraction values on internal dose assessment. The radionuclide was selected for two reasons: 1) it was a beta emitting radionuclide; and 2) the annual limit on intake for ingestion was based on the non-stochastic committed dose equivalent limit to the lower large intestine. The calculated annual limit on intake was found to be three times greater than the annual limit on intake provided in ICRP Publication 30. There are many radionuclides that have a section of the GI tract as the limiting organ for ingestion. It is expected that the annual limit on intake value for these radionuclides would increase when the revised GI tract model is employed for internal dose assessment.