Mycophenolate Mofetil for the Treatment of Autoimmune Hepatitis in Patients Refractory to Standard Therapy

There are limited therapeutic options available for patients with autoimmune hepatitis in whom conventional treatment fails. A case series of five patients unresponsive to or unable to take azathioprine, 6-mercaptopurine or corticosteroids who were treated with mycophenolate mofetil (MMF) is reported. While on MMF, alanine aminotransferase normalized or remained normal in all patients. MMF had a steroid-sparing effect and histological remission was demonstrated in one patient after seven months of MMF. One patient experienced an uncomplicated episode of pyelonephritis. In conclusion, MMF can effectively induce and maintain remission in refractory autoimmune hepatitis patients

Evolution of trace gases and particles emitted by a chaparral fire in California

Biomass burning (BB) is a major global source of trace gases and particles. Accurately representing the production and evolution of these emissions is an important goal for atmospheric chemical transport models. We measured a suite of gases and aerosols emitted from an 81 hectare prescribed fire in chaparral fuels on the central coast of California, US on 17 November 2009. We also measured physical and chemical changes that occurred in the isolated downwind plume in the first ~4 h after emission. The measurements were carried out onboard a Twin Otter aircraft outfitted with an airborne Fourier transform infrared spectrometer (AFTIR), aerosol mass spectrometer (AMS), single particle soot photometer (SP2), nephelometer, LiCor CO_2 analyzer, a chemiluminescence ozone instrument, and a wing-mounted meteorological probe. Our measurements included: CO_2; CO; NO_x; NH_3; non-methane organic compounds; organic aerosol (OA); inorganic aerosol (nitrate, ammonium, sulfate, and chloride); aerosol light scattering; refractory black carbon (rBC); and ambient temperature, relative humidity, barometric pressure, and three-dimensional wind velocity. The molar ratio of excess O_3 to excess CO in the plume (ΔO_3/ΔCO) increased from −5.13 (±1.13) × 10^(−3) to 10.2 (±2.16) × 10^(−2) in ~4.5 h following smoke emission. Excess acetic and formic acid (normalized to excess CO) increased by factors of 1.73 ± 0.43 and 7.34 ± 3.03 (respectively) over the same time since emission. Based on the rapid decay of C_2H_4 we infer an in-plume average OH concentration of 5.27 (±0.97) × 10^6 molec cm^(−3), consistent with previous studies showing elevated OH concentrations in biomass burning plumes. Ammonium, nitrate, and sulfate all increased over the course of 4 h. The observed ammonium increase was a factor of 3.90 ± 2.93 in about 4 h, but accounted for just ~36% of the gaseous ammonia lost on a molar basis. Some of the gas phase NH_3 loss may have been due to condensation on, or formation of, particles below the AMS detection range. NO_x was converted to PAN and particle nitrate with PAN production being about two times greater than production of observable nitrate in the first ~4 h following emission. The excess aerosol light scattering in the plume (normalized to excess CO_2) increased by a factor of 2.50 ± 0.74 over 4 h. The increase in light scattering was similar to that observed in an earlier study of a biomass burning plume in Mexico where significant secondary formation of OA closely tracked the increase in scattering. In the California plume, however, ΔOA/ΔCO_2 decreased sharply for the first hour and then increased slowly with a net decrease of ~20% over 4 h. The fraction of thickly coated rBC particles increased up to ~85% over the 4 h aging period. Decreasing OA accompanied by increased scattering/particle coating in initial aging may be due to a combination of particle coagulation and evaporation processes. Recondensation of species initially evaporated from the particles may have contributed to the subsequent slow rise in OA. We compare our results to observations from other plume aging studies and suggest that differences in environmental factors such as smoke concentration, oxidant concentration, actinic flux, and RH contribute significantly to the variation in plume evolution observations

Solid-State and Gas-Phase Structures and Energetic Properties of the Dangerous Methyl and Fluoromethyl Nitrates

Reichel M, Krumm B, Vishnevskiy Y, et al. Solid-State and Gas-Phase Structures and Energetic Properties of the Dangerous Methyl and Fluoromethyl Nitrates. Angewandte Chemie (International ed. in English). 2019;58(51):18557-18561.An improved synthesis of the simplest nitric acid ester, methyl nitrate, and a new synthesis of fluoromethyl nitrate use the metathesis of the corresponding iodomethanes with silver nitrate. Both compounds were identified by spectroscopy and the structures determined for in situ grown crystals by X-ray diffraction as well as in the gas phase by electron diffraction. Fluorination leads to structures with shorter C-O and N-O bonds, has an energetically destabilizing effect and increases friction sensitivity, but decreases detonation performance. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA

Urticaire chronique superficielle associée aux cancers solides : un cas et revue de la littérature

BACKGROUND: Chronic urticaria is common and is generally idiopathic ("spontaneous"). Links between solid cancer and chronic urticaria have been mentioned in the literature. PATIENTS AND METHODS: We report the case of a 63-year-old man presenting with superficial chronic urticaria associated with adenocarcinoma of the ethmoid sinus. We discuss the possibility of systemic origin in light of the severity of the disease and its resistance to treatment. Only recurrent ethmoidal cancer was highlighted. Curative care resulted in complete resolution of the urticaria without relapse at 32 months of follow-up. DISCUSSION: In a literature review, we collected 17 cases of superficial chronic urticaria associated with cancer. These cases were marked by synchronous progression and by the inefficacy (86%) of anti-histamines and systemic corticosteroids. Although cases of chronic superficial urticaria associated with cancer remain rare, the condition merits discussion due to its severity and significant resistance to therapy

Evolution of Trace Gases and Particles Emitted by a Chaparral Fire in California

Biomass burning (BB) is a major global source of trace gases and particles. Accurately representing the production and evolution of these emissions is an important goal for atmospheric chemical transport models. We measured a suite of gases and aerosols emitted from an 81 hectare prescribed fire in chaparral fuels on the central coast of California, US on 17 November 2009. We also measured physical and chemical changes that occurred in the isolated down-wind plume in the first similar to 4 h after emission. The measurements were carried out onboard a Twin Otter aircraft outfitted with an airborne Fourier transform infrared spectrometer (AFTIR), aerosol mass spectrometer (AMS), single particle soot photometer (SP2), nephelometer, LiCor CO2 analyzer, a chemiluminescence ozone instrument, and a wing-mounted meteorological probe. Our measurements included: CO2; CO; NOx; NH3; non-methane organic compounds; organic aerosol (OA); inorganic aerosol (nitrate, ammonium, sulfate, and chloride); aerosol light scattering; refractory black carbon (rBC); and ambient temperature, relative humidity, barometric pressure, and three-dimensional wind velocity. The molar ratio of excess O-3 to excess CO in the plume (Delta O-3/Delta CO) increased from -5.13 (+/- 1.13) x 10(-3) to 10.2 (+/- 2.16) x 10(-2) in similar to 4.5 h following smoke emission. Excess acetic and formic acid (normalized to excess CO) increased by factors of 1.73 +/- 0.43 and 7.34 +/- 3.03 (respectively) over the same time since emission. Based on the rapid decay of C2H4 we infer an in-plume average OH concentration of 5.27 (+/- 0.97) x 10(6) molec cm(-3), consistent with previous studies showing elevated OH concentrations in biomass burning plumes. Ammonium, nitrate, and sulfate all increased over the course of 4 h. The observed ammonium increase was a factor of 3.90 +/- 2.93 in about 4 h, but accounted for just similar to 36% of the gaseous ammonia lost on a molar basis. Some of the gas phase NH3 loss may have been due to condensation on, or formation of, particles below the AMS detection range. NOx was converted to PAN and particle nitrate with PAN production being about two times greater than production of observable nitrate in the first similar to 4 h following emission. The excess aerosol light scattering in the plume (normalized to excess CO2) increased by a factor of 2.50 +/- 0.74 over 4 h. The increase in light scattering was similar to that observed in an earlier study of a biomass burning plume in Mexico where significant secondary formation of OA closely tracked the increase in scattering. In the California plume, however, Delta OA/Delta CO2 decreased sharply for the first hour and then increased slowly with a net decrease of similar to 20% over 4 h. The fraction of thickly coated rBC particles increased up to similar to 85% over the 4 h aging period. Decreasing OA accompanied by increased scattering/particle coating in initial aging may be due to a combination of particle coagulation and evaporation processes. Recondensation of species initially evaporated from the particles may have contributed to the subsequent slow rise in OA. We compare our results to observations from other plume aging studies and suggest that differences in environmental factors such as smoke concentration, oxidant concentration, actinic flux, and RH contribute significantly to the variation in plume evolution observations

Airborne characterization of smoke marker ratios from prescribed burning

A Particle-Into-Liquid Sampler – Total Organic Carbon (PILS-TOC) and fraction collector system was flown aboard a Twin Otter aircraft sampling prescribed burning emissions in South Carolina in November 2011 to obtain smoke marker measurements. The fraction collector provided 2 min time-integrated offline samples for carbohydrate (i.e., smoke markers levoglucosan, mannosan, and galactosan) analysis by high-performance anion-exchange chromatography with pulsed amperometric detection. Each fire location appeared to have a unique 1levoglucosan /1water-soluble organic carbon (WSOC) ratio (RF01/RF02/RF03/RF05 = 0.163± 0.007 μg C μg−1 C, RF08 = 0.115 ± 0.011 μg C μg−1 C, RF09A = 0.072 ± 0.028 μgC μg−1 C, and RF09B = 0.042 ± 0.008 μg Cμg−1 C, where RF means research flight). These ratios were comparable to those obtained from controlled laboratory burns and suggested that the emissions sampled during RF01/F02/RF03/RF05 were dominated by the burning of grasses, RF08 by leaves, RF09A by needles, and RF09B by marsh grasses. These findings were further supported by the 1galactosan /1levoglucosan ratios (RF01/RF02/RF03/RF05 = 0.067 ± 0.004 μg μg−1, RF08 = 0.085 ± 0.009 μg μg−1, and RF09A = 0.101 ± 0.029 μg μg−1) obtained as well as by the ground-based fuel and filter sample analyses during RF01/RF02/RF03/RF05. Differences between 1potassium /1levoglucosan ratios obtained for these prescribed fires vs. laboratory-scale measurements suggest that some laboratory burns may not accurately represent potassium emissions from prescribed burns. The1levoglucosan /1WSOC ratio had no clear dependence on smoke age or fire dynamics suggesting that this ratio is more dependent on the type of fuel being burned. Levoglucosan was stable over a timescale of at least 1.5 h and could be useful to help estimate the air quality impacts of biomass burning

Aerosol emissions from prescribed fires in the United States: A synthesis of laboratory and aircraft measurements

Aerosol emissions from prescribed fires can affect air quality on regional scales. Accurate representation of these emissions in models requires information regarding the amount and composition of the emitted species. We measured a suite of submicron particulate matter species in young plumes emitted from prescribed fires (chaparral and montane ecosystems in California; coastal plain ecosystem in South Carolina) and from open burning of over 15 individual plant species in the laboratory. We report emission ratios and emission factors for refractory black carbon (rBC) and submicron nonrefractory aerosol and compare field and laboratory measurements to assess the representativeness of our laboratory-measured emissions. Laboratory measurements of organic aerosol (OA) emission factors for some fires were an order of magnitude higher than those derived from any of our aircraft observations; these are likely due to higher-fuel moisture contents, lower modified combustion efficiencies, and less dilution compared to field studies. Nonrefractory inorganic aerosol emissions depended more strongly on fuel type and fuel composition than on combustion conditions. Laboratory and field measurements for rBC were in good agreement when differences in modified combustion efficiency were considered; however, rBC emission factors measured both from aircraft and in the laboratory during the present study using the Single Particle Soot Photometer were generally higher than values previously reported in the literature, which have been based largely on filter measurements. Although natural variability may account for some of these differences, an increase in the BC emission factors incorporated within emission inventories may be required, pending additional field measurements for a wider variety of fires

T cells are dominant population in human abdominal aortic aneurysms and their infiltration in the perivascular tissue correlates with disease severity

Abdominal Aortic Aneurysm (AAA) is a major cause of cardiovascular mortality. Adverse changes in vascular phenotype act in concert with chronic inflammation to promote AAA progression. Perivascular adipose tissue (PVAT) helps maintain vascular homeostasis but when inflamed and dysfunctional, can also promote vascular pathology. Previous studies suggested that PVAT may be an important site of vascular inflammation in AAA; however, a detailed assessment of leukocyte populations in human AAA, their anatomic location in the vessel wall and correlation to AAA size remain undefined. Accordingly, we performed in depth immunophenotyping of cells infiltrating the pathologically altered perivascular tissue (PVT) and vessel wall in AAA samples at the site of maximal dilatation (n=51 patients). Flow cytometry revealed that T cells, rather than macrophages, are the major leukocyte subset in AAA and that their greatest accumulations occur in PVT. Both CD4+ and CD8+ T cell populations are highly activated in both compartments, with CD4+ T cells displaying the highest activation status within the AAA wall. Finally, we observed a positive relationship between T cell infiltration in PVT and AAA wall. Interestingly, only PVT T cell infiltration was strongly related to tertiles of AAA size. In summary, this study highlights an important role for PVT as a reservoir of T lymphocytes and potentially as a key site in modulating the underlying inflammation in AAA

Measurements of reactive trace gases and variable O3 formation rates in some South Carolina biomass burning plumes

In October–November 2011 we measured trace gas emission factors from seven prescribed fires in South Carolina (SC), US, using two Fourier transform infrared spectrometer (FTIR) systems and whole air sampling (WAS) into canisters followed by gas-chromatographic analysis. A total of 97 trace gas species were quantified from both airborne and ground-based sampling platforms, making this one of the most detailed field studies of fire emissions to date. The measurements include the first emission factors for a suite of monoterpenes produced by heating vegetative fuels during field fires. The first quantitative FTIR observations of limonene in smoke are reported along with an expanded suite of monoterpenes measured by WAS including α-pinene, β-pinene, limonene, camphene, 4-carene, and myrcene. The known chemistry of the monoterpenes and their measured abundance of 0.4–27.9% of non-methane organic compounds (NMOCs) and ~ 21% of organic aerosol (mass basis) suggests that they impacted secondary formation of ozone (O3), aerosols, and small organic trace gases such as methanol and formaldehyde in the sampled plumes in the first few hours after emission. The variability in the initial terpene emissions in the SC fire plumes was high and, in general, the speciation of the initially emitted gas-phase NMOCs was 13–195% different from that observed in a similar study in nominally similar pine forests in North Carolina ~ 20 months earlier. It is likely that differences in stand structure and environmental conditions contributed to the high variability observed within and between these studies. Similar factors may explain much of the variability in initial emissions in the literature. The ΔHCN/ΔCO emission ratio, however, was found to be fairly consistent with previous airborne fire measurements in other coniferous-dominated ecosystems, with the mean for these studies being 0.90 ± 0.06%, further confirming the value of HCN as a biomass burning tracer. The SC results also support an earlier finding that C3-C4 alkynes may be of use as biomass burning indicators on the time-scale of hours to a day. It was possible to measure the downwind chemical evolution of the plume on four of the fires and significant O3 formation (ΔO3/ΔCO from 10–90%) occurred in all of these plumes within two hours. The slowest O3 production was observed on a cloudy day with low co-emission of NOx. The fastest O3 production was observed on a sunny day when the downwind plume almost certainly incorporated significant additional NOx by passing over the Columbia, SC metropolitan area. Due to rapid plume dilution, it was only possible to acquire high-quality downwind data for two other trace gas species (formaldehyde and methanol) during two of the fires. In all four of these cases, significant increases in formaldehyde and methanol were observed in \u3c2 h. This is likely the first direct observation of post-emission methanol production in biomass burning plumes. Post-emission production of methanol does not always happen in young biomass burning plumes, and its occurrence in this study could have involved terpene precursors to a significant extent