Pyrocumulonimbus affect average stratospheric aerosol composition.

Pyrocumulonimbus (pyroCb) are wildfire-generated convective clouds that can inject smoke directly into the stratosphere. PyroCb have been tracked for years, yet their apparent rarity and episodic nature lead to highly uncertain climate impacts. In situ measurements of pyroCb smoke reveal its distinctive and exceptionally stable aerosol properties and define the long-term influence of pyroCb activity on the stratospheric aerosol budget. Analysis of 13 years of airborne observations shows that pyroCb are responsible for 10 to 25% of the black carbon and organic aerosols in the "present-day" lower stratosphere, with similar impacts in both the North and South Hemispheres. These results suggest that, should pyroCb increase in frequency and/or magnitude in future climates, they could generate dominant trends in stratospheric aerosol.

The Role of Sulfur Dioxide in Stratospheric Aerosol Formation Evaluated Using In-Situ Measurements in the Tropical Lower Stratosphere.

Stratospheric aerosols (SAs) are a variable component of the Earth's albedo that may be intentionally enhanced in the future to offset greenhouse gases (geoengineering). The role of tropospheric-sourced sulfur dioxide (SO2) in maintaining background SAs has been debated for decades without in-situ measurements of SO2 at the tropical tropopause to inform this issue. Here we clarify the role of SO2 in maintaining SAs by using new in-situ SO2 measurements to evaluate climate models and satellite retrievals. We then use the observed tropical tropopause SO2 mixing ratios to estimate the global flux of SO2 across the tropical tropopause. These analyses show that the tropopause background SO2 is about 5 times smaller than reported by the average satellite observations that have been used recently to test atmospheric models. This shifts the view of SO2 as a dominant source of SAs to a near-negligible one, possibly revealing a significant gap in the SA budget.

Transport of ice into the stratosphere and the humidification of the stratosphere over the 21st century.

Climate models predict that tropical lower-stratospheric humidity will increase as the climate warms. We examine this trend in two state-of-the-art chemistry-climate models. Under high greenhouse gas emissions scenarios, the stratospheric entry value of water vapor increases by ~1 part per million by volume (ppmv) over this century in both models. We show with trajectory runs driven by model meteorological fields that the warming tropical tropopause layer (TTL) explains 50-80% of this increase. The remainder is a consequence of trends in evaporation of ice convectively lofted into the TTL and lower stratosphere. Our results further show that, within the models we examined, ice lofting is primarily important on long time scales - on interannual time scales, TTL temperature variations explain most of the variations in lower stratospheric humidity. Assessing the ability of models to realistically represent ice-lofting processes should be a high priority in the modeling community.

Evaluation of UT/LS hygrometer accuracy by intercomparison during the NASA MACPEX mission.

Acquiring accurate measurements of water vapor at the low mixing ratios (< 10 ppm) encountered in the upper troposphere and lower stratosphere (UT/LS) has proven to be a significant analytical challenge evidenced by persistent disagreements between high-precision hygrometers. These disagreements have caused uncertainties in the description of the physical processes controlling dehydration of air in the tropical tropopause layer and entry of water into the stratosphere and have hindered validation of satellite water vapor retrievals. A 2011 airborne intercomparison of a large group of in situ hygrometers onboard the NASA WB-57F high-altitude research aircraft and balloons has provided an excellent opportunity to evaluate progress in the scientific community toward improved measurement agreement. In this work we intercompare the measurements from the Midlatitude Airborne Cirrus Properties Experiment (MACPEX) and discuss the quality of agreement. Differences between values reported by the instruments were reduced in comparison to some prior campaigns but were nonnegligible and on the order of 20% (0.8 ppm). Our analysis suggests that unrecognized errors in the quantification of instrumental background for some or all of the hygrometers are a likely cause. Until these errors are understood, differences at this level will continue to somewhat limit our understanding of cirrus microphysical processes and dehydration in the tropical tropopause layer.

Stratospheric water vapor feedback.

We show here that stratospheric water vapor variations play an important role in the evolution of our climate. This comes from analysis of observations showing that stratospheric water vapor increases with tropospheric temperature, implying the existence of a stratospheric water vapor feedback. We estimate the strength of this feedback in a chemistry-climate model to be +0.3 W/(m(2)⋅K), which would be a significant contributor to the overall climate sensitivity. One-third of this feedback comes from increases in water vapor entering the stratosphere through the tropical tropopause layer, with the rest coming from increases in water vapor entering through the extratropical tropopause.

Quantifying stratospheric ozone in the upper troposphere with in situ measurements of HCl.

We have developed a chemical ionization mass spectrometry technique for precise in situ measurements of hydrochloric acid (HCl) from a high-altitude aircraft. In measurements at subtropical latitudes, minimum HCl values found in the upper troposphere (UT) were often near or below the detection limit of the measurements (0.005 parts per billion by volume), indicating that background HCl values are much lower than a global mean estimate. However, significant abundances of HCl were observed in many UT air parcels, as a result of stratosphere-to-troposphere transport events. We developed a method for diagnosing the amount of stratospheric ozone in these UT parcels using the compact linear correlation of HCl with ozone found throughout the lower stratosphere (LS). Expanded use of this method will lead to improved quantification of cross-tropopause transport events and validation of global chemical transport models.

Evidence that nitric acid increases relative humidity in low-temperature cirrus clouds.

In situ measurements of the relative humidity with respect to ice (RHi) and of nitric acid (HNO3) were made in both natural and contrail cirrus clouds in the upper troposphere. At temperatures lower than 202 kelvin, RHi values show a sharp increase to average values of over 130% in both cloud types. These enhanced RHi values are attributed to the presence of a new class of HNO3-containing ice particles (Delta-ice). We propose that surface HNO3 molecules prevent the ice/vapor system from reaching equilibrium by a mechanism similar to that of freezing point depression by antifreeze proteins. Delta-ice represents a new link between global climate and natural and anthropogenic nitrogen oxide emissions. Including Delta-ice in climate models will alter simulated cirrus properties and the distribution of upper tropospheric water vapor.

Factors associated with progression of IgA nephropathy are related to renal function--a model for estimating risk of progression in mild disease.

BACKGROUND: A number of factors are linked to the outcome of IgA nephropathy (IgAN). However, it has been difficult to compare results of studies since patient populations have varied greatly. There were 3 aims in the study reported here, namely to compare factors associated with renal outcome in IgAN patients with different levels of renal function on diagnosis; to determine factors which were independently associated with progression of renal disease in initially mild IgAN; and to create a model for the estimation of the risk of progression in individual IgAN patients with normal renal function on diagnosis. METHODS: Two hundred and fifty-nine IgAN patients who had been followed on average for 9.1 (SD 4.5) after diagnosis were divided into 2 groups on the basis of renal function on diagnosis. In group 1 (98 patients), Ccr (creatinine clearance, estimated by the Cockcroft-Gault formula) was < 85 ml/min, in group 2 (161 patients) > or = 85 ml/min. Univariate analyses were used to find significant differences between progressors and non-progressors in both groups. Logistic regression analysis was used to determine factors independently associated with progression in group 2. RESULTS: Several factors were found to be associated with outcome in both groups, such as hypertension, level of Ccr, serum cholesterol, proteinuria, and also histopathological changes. Factors associated with progression in patients with initially decreased renal function (group 1), were predictable, such as male sex, absence of episodes of macroscopic hematuria, serum urate level and degree of tubular atrophy. Surprisingly, in patients with initially normal renal function (group 2), numbers of urinary erythrocytes were associated with outcome. The factors independently associated with progression in this group were number of urinary erythrocytes, existence of hypertension and in histopathology arteriolosclerosis and the level of glomerular score. A model for estimating risk of progression on the basis of various combinations of factors found to be independently associated with outcome is presented. CONCLUSIONS: We concluded that association between variable and outcome in IgAN depends partly on renal function at the time of assessment of the factor. Since there are factors which are independently associated with the outcome of early and apparently mild disease, early diagnosis of IgAN is desirable: outcome in mild IgAN can be predicted reliably on the basis of factors found to be independently associated with outcome.

Catalytically active iron and bacterial growth in serum of haemodialysis patients after i.v. iron-saccharate administration.

BACKGROUND: I.v. iron is commonly administered to haemodialysis patients suffering from anaemia to improve their response to erythropoietin therapy. It has been unclear whether routinely used doses of i.v. iron preparations could result in iron release into plasma in amounts exceeding the iron binding capacity of transferrin. Here, we have studied the effect of 100 mg of iron saccharate given as an i.v. injection on transferrin saturation and the appearance of potentially harmful catalytically active iron. METHODS: We followed serum iron, transferrin and transferrin-saturation before and 5-210 min after administration of iron saccharate in 12 patients on chronic haemodialysis due to end-stage renal disease. We measured catalytically active iron by the bleomycin-detectable iron (BDI) assay and transferrin iron forms by urea gel electrophoresis, and studied iron-dependent growth of Staphylococcus epidermidis inoculated into the serum samples in vitro. RESULTS: The iron saccharate injection resulted in full transferrin saturation and appearance of BDI in the serum in seven out of the 12 patients. BDI appeared more often in patients with a low serum transferrin concentration, but it was not possible to identify patients at risk based on serum transferrin or ferritin level before i.v. iron. The average transferrin saturation and BDI level increased until the end of the follow-up time of 3.5 h. The appearance of BDI resulted in loss of the ability of patient serum to resist the growth of S. epidermidis, which was restored by adding iron-free apotransferrin to the serum. Iron saccharate, added to serum in vitro, released only little iron and promoted only slow bacterial growth, but caused falsely high transferrin saturation by one routinely used serum iron assay. CONCLUSIONS: The results indicate that 100 mg of iron saccharate often leads to transferrin oversaturation and the presence of catalytically active iron within 3.5 h after i.v. injection. As catalytically active iron is potentially toxic and may promote bacterial growth, it may be recommendable to use dosage regimens for i.v. iron that would not cause transferrin oversaturation.

Ocular findings in 34 patients with Alport syndrome: correlation of the findings to mutations in COL4A5 gene.

PURPOSE: To describe the incidence and type of ocular findings of 34 patients with Alport syndrome and to analyze the association of gene defect in COL4A5 gene to ocular abnormalities found. METHODS: A nationwide search of Alport syndrome patients was performed in Finland, and patients were invited to take part in a thorough ophthalmologic investigation. RESULTS: A total of 34 Alport syndrome patients from 14 different pedigrees were examined, and ocular abnormalities were found in 32% of them. The visual acuities were normal except in 4 of the 34 patients. Six individuals had retinal flecks and 4 men had anterior lenticonus. In 57% of the pedigrees the defect in COL4A5 gene was known. CONCLUSION: Ocular abnormalities were rare in childhood and increased with age. There was no correlation between the type of mutation and the type of ocular changes. In addition, the penetrance of the ocular findings varied considerably within most families.

Iron availability is transiently improved by intravenous iron medication in patients on chronic hemodialysis.

Iron deficiency is common in hemodialysis patients, particularly if they are on recombinant human erythropoietin (rHuEPO) therapy. Ten anemic patients (hemoglobin concentration 89 +/- 2.2 g/l, mean +/- SEM) on hemodialysis with either storage (serum-ferritin < 60 mg/l) and/or functional (S-transferrin saturation < or = 17%) iron deficiency were followed for 5 weeks. During the first 3 weeks they were given 100 mg of iron dextran on 10 consecutive dialysis sessions. Half of the patients were concomitantly treated with rHuEPO. Iron therapy resulted in a rapid elevation in serum transferrin iron saturation from 11 +/- 1.5% to 80 +/- 7.2% (p < 0.0001), but it decreased to pre-treatment levels within 2 weeks after discontinuation of iron therapy. Serum ferritin concentration increased from 157 +/- 73 mg/l to 434 +/- 105 mg/l during iron therapy (p < 0.0001). In spite of this only 4 patients (2 rHuEPO treated) responded and had a hemoglobin increment > 10 g/l. In the whole group serum transferrin receptor (TfR) levels remained stable, but increased after the cessation of iron dextran only in the rHuEPO treated patients (p < 0.01). In the responders the TfR levels were higher during iron therapy than in the nonresponders (p < 0.02). In an attempt to explain the resistance to iron therapy, serum concentrations of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1b (IL-1b) were also analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of exogenous erythropoietin on haem synthesis in anaemic patients with rheumatoid arthritis.

The effect of recombinant human erythropoietin (rHuEPO) on haem biosynthesis in peripheral red blood cells was evaluated in 12 patients with RA and anaemia (mean haemoglobin concentration 102 g/l, range 90-109 g/l). Before treatment, the serum concentrations of erythropoietin (EPO) were low (mean 13 pmol/l, range 5-32 pmol/l), the activities of haem-synthesizing enzymes within the reference intervals and the erythrocyte protoporphyrin (E-PROTO) concentrations clearly higher than normal. Nine patients responded with an increase in the haemoglobin level of 15 g/l or more. rHuEPO induced a rise in the mean haem synthase (HAEM-S) activity from a baseline of 12.1 to a maximum of 26.8 pmol/h per 10(6) reticulocytes after 20 weeks of treatment (P < 0.002). The mean E-PROTO concentration also rose and reached its maximum at 8 weeks of treatment. We conclude that correction of anaemia in patients with RA using rHuEPO is associated with an activation of HAEM-S, commonly regarded as the rate-limiting enzyme of haem synthesis in erythroid cells. Functional iron deficiency probably explains the simultaneous rise in E-PROTO concentration.

Successful treatment of the anemia of rheumatoid arthritis with subcutaneously administered recombinant human erythropoietin. Slower response in patients with more severe inflammation.

We performed a 24-week open clinical study in which 12 patients with rheumatoid arthritis (RA) and anemia (mean hemoglobin (Hb) value 102 g/l, range 90-109 g/l) were treated with recombinant human erythropoietin (rHuEPO). rHuEPO was given as a subcutaneous injection twice weekly with an initial dose of 300 U/kg/week. Nine of the 11 patients who completed the study responded with an increase in Hb value of 15 g/l or more within 3 to 17 weeks. Three months after treatment the Hb levels were significantly lower than the highest Hb levels (p < 0.0001). There was an inverse correlation between the response rate and the mean serum concentrations of C-reactive protein and serum amyloid A protein (p < 0.001 and p < 0.003, respectively). We conclude that rHuEPO can correct anemia in patients with RA, but the response seems to be adversely influenced by the inflammatory activity of the disease.

Raised plasma endothelin-I concentration following cold pressor test.

Plasma concentration of immunoreactive endothelin-1 was measured by radioimmunoassay in 6 healthy subjects before and following cold pressor test by immersion of one fore-arm into ice-water. Mean (SEM) plasma endothelin-1 concentration rose from 1.2 (0.7) to peak value 8.4 (2.3) pg/ml in venous plasma from the immersed hand, and, reaching peak 2 minutes later, from 1.4 (0.5) to 4.6 (2.3) pg/ml in venous plasma from the contralateral hand. In 66 healthy control subjects, venous plasma concentration of endothelin-1 was 2.9 +/- 1.2 pg/ml (mean +/- SD). Exposure to cold is associated with raised blood levels of endothelin-1, which points to a relation between endothelin-1 and vasoconstriction associated with low temperature.

Erythropoietin, aluminium, and anaemia in patients on haemodialysis.

Effects of erythropoietin treatment on haem synthesis in peripheral blood were evaluated in 11 patients on haemodialysis. After 2 weeks of erythropoietin, mean (SEM) uroporphyrinogen-l synthase activity increased significantly from 88 (10) to 116 (9) pmol/h per mg protein. Haem synthase activity, thought to be the rate-limiting step in erythroid haem synthesis, also showed a significant increase from 4.5 (0.8) to 8.4 (1.8) pmol/h per 10(6) reticulocytes. 4 patients, who showed only a partial response to erythropoietin, had significantly higher serum aluminium concentrations than the 7 who responded fully (225 [44] vs 55 [23] micrograms/l); erythrocyte protoporphyrin concentrations in partial responders were also much higher than in responders (973 [120] vs 388 [29] nmol/l). Aluminium intoxication may cause resistance to erythropoietin by interference with haem synthesis, with accumulation of protoporphyrin.

Beneficial effects of erythropoietin on haematological parameters, aerobic capacity, and body fluid composition in patients on haemodialysis.

Eleven patients on haemodialysis were treated with erythropoietin (EPO), 50-200 U kg-1 once to three times a week, for up to 1 year. After outset of EPO all patients became transfusion-independent. Four patients did not reach the target haemoglobin (Hb) level 100 g l-1 in 5 months. These patients had higher serum concentrations of aluminium (225 +/- 87 micrograms l-1, mean +/- SD) than the responding patients (55 +/- 56 micrograms l-1). Addition of desferrioxamine to treatment with EPO resulted in a rapid rise in Hb values in these patients. Thus, aluminium may inhibit EPO responsiveness. All patients were iron overloaded. Serum ferritin levels declined in all but one patient with secondary haemochromatosis. In exercise tests the aerobic capacity and oxygen uptake increased during EPO therapy. Peak oxygen consumption (Vo2 peak), oxygen pulse, oxygen uptake at anaerobic threshold (AT) and total work output (W max) increased 19%, 36%, 26% and 24%, respectively. Lean body mass (LBM) increased by 8%. Taken together, all clinical EPO effects measured appeared clinically favourable.

High serum erythropoietin levels are normalized during treatment of congestive heart failure with enalapril.

Eighteen patients with dilated cardiomyopathy (three female, mean age 57 years), were treated for 48 weeks with enalapril added to digoxin and diuretic therapy for congestive heart failure of New York Heart Association (NYHA) functional class II (three patients). III (eight patients) and IV (seven patients), respectively. Serum levels of erythropoietin (EPO) were raised at the start (37 +/- 12.8 pmol 1(-1); mean +/- SD) and were normalized during enalapril treatment (17.5 +/- 9.9 pmol 1(-1) at 48 weeks; P less than 0.001). Serum EPO correlated at the start with NYHA functional class (r = 0.68; P less than 0.05). Normalization of elevated serum EPO concentrations during treatment with enalapril paralleled clinical and haemodynamic improvement, and probably reflected relief from renal hypoxia.