Severe Painful Vaso-Occlusive Crises and Mortality in a Contemporary Adult Sickle Cell Anemia Cohort Study

Background

Frequent painful vaso-occlusive crises (VOCs) were associated with mortality in the Cooperative Study of Sickle Cell Disease (CSSCD) over twenty years ago. Modern therapies for sickle cell anemia (SCA) like hydroxyurea are believed to have improved overall patient survival. The current study sought to determine the relevance of the association between more frequent VOCs and death and its relative impact upon overall mortality compared to other known risk factors in a contemporary adult SCA cohort.

Methods

Two hundred sixty four SCA adults were assigned into two groups based on patient reported outcomes for emergency department (ED) visits or hospitalizations for painful VOC treatment during the 12 months prior to evaluation.

Results

Higher baseline hematocrit (p = 0.0008), ferritin (p = 0.005), and HDL cholesterol (p = 0.01) were independently associated with 1 or more painful VOCs requiring an ED visit or hospitalization for acute pain. During a median follow-up of 5 years, mortality was higher in the ED visit/hospitalization group (relative risk [RR] 2.68, 95% CI 1.1-6.5, p = 0.03). Higher tricuspid regurgitatant jet velocity (TRV) (RR 2.41, 95% CI 1.5-3.9, p < 0.0001), elevated ferritin (RR 4.00, 95% CI 1.8-9.0, p = 0.001) and lower glomerular filtration rate (RR=2.73, 95% CI 1.6-4.6, p < 0.0001) were also independent risk factors for mortality.

Conclusions

Severe painful VOCs remain a marker for SCA disease severity and premature mortality in a modern cohort along with other known risk factors for death including high TRV, high ferritin and lower renal function. The number of patient reported pain crises requiring healthcare utilization is an easily obtained outcome that could help to identify high risk patients for disease modifying therapies.

Trial Registration

ClinicalTrials.gov NCT00011648 http://clinicaltrials.gov/     

Effects of medium viscosity on kinetics of the enzymatic reaction catalyzed by bacterial RNase

Effects of medium viscosity on kinetic parameters of poly(U) hydrolysis catalyzed by RNase from Bac. intermedius 7P (binase) were studied in solutions of sucrose (4-50 wt. %) and glycerol (35-62 wt. %) in Tris--sodium acetate buffer (pH 7.5) at 25 degreesC. The rate constant of reaction kcat was practically unchanged over a wide range of viscosities (1-15 cP for sucrose and 2.5-3 cP for glycerol). In glycerol solutions, kcat slightly increased with viscosity increase from 4 to 10 cP. Addition of NaCl to the buffer medium resulted in an inhibitory effect of Na+ on kcat, prevented by 50% sucrose or 60% glycerol. It is concluded that binase-catalyzed poly(U) cleavage occurs through a "tense"-substrate mechanism, similarly to reactions catalyzed by alpha-chymotrypsin, trypsin, and laccase.     

A web server to locate periodicities in a sequence

Summary : FT is a tool written in C++, which implements the Fourier analysis method to locate periodicities in aminoacid or DNA sequences. It is provided for free public use on a WWW server with a Java interface. Availability : The server address is http://o2.db. uoa.gr/FT Contact : shamodr@atlas.uoa.gr      

Neutron emission generated in the collision of plasma flows in the presence of an external magnetic field

Results are presented from experimental studies of the neutron emission generated in the collision of deuterium plasma flows produced in discharges in crossed E × H fields and propagating in opposite directions in a neutral gas across an external magnetic field. It is shown that the interaction of oppositely propagating deuterium plasma flows gives rise to the generation of soft X-ray emission and neutron emission from the dd reaction (dd → ³He + n) and is accompanied by an almost complete depolarization of the flows and rapid variations in the magnetic field (at a rate of ～10¹¹ G/s). The measurements were performed at energies and velocities of the flows of up to 600 J and 3.5 × 10⁷ cm/s, respectively. The plasma density in each flow was ～10¹⁵ cm^?3. The upper estimates for the astrophysical S factor and the effective cross sections of the dd reaction obtained from our measurements are compared to theoretical calculations and to the results of experiments performed in the MIG high-current accelerator (Institute of High-Current Electronics, Russian Academy of Sciences, Tomsk).     

Uncoupler of Oxidative Phosphorylation Prolongs the Lifespan of <Emphasis Type="Italic">Drosophila</Emphasis>

The effect of a moderate ("soft") uncoupling of mitochondria on the lifespan and some parameters of biological age of Drosophila melanogaster strain Oregon was studied. Addition of the uncoupler 2,4-dinitrophenol (DNP) to the nutritional mixture of larvae significantly increased the average lifespan of the flies without changing their maximal lifespan. DNP significantly increased the rate of oxygen consumption by isolated mitochondria and tissue homogenates of the flies in state 4 (of Chance). DNP also decreased the activity of alcohol dehydrogenase (a parameter of flies' biological age) in the tissue homogenates, especially on octanol as the reaction substrate. However, being deprived of food the DNP-treated flies displayed a markedly decreased viability as compared to the control flies. On the whole, the results suggest that "soft" uncoupling of mitochondria may increase the lifespan.     

Synthesis, conformational characteristics and anti-influenza virus A activity of some 2-adamantylsubstituted azacycles

The broad-spectrum antiviral activity of 2-(2-adamantyl)piperidines 11, 13a,b, and 15, 3-(2-adamantyl)pyrrolidines 27, 21a-g and 2-(2-adamantylmethyl)piperidines 30, 32a-c, and 35a-d was examined. Several compounds in the new series were potent against influenza A H(3)N(2) virus. When 1-aminoethyl pharmacophore group of 2-rimantadine 4 (2-isomer of rimantadine) is included into a saturated nitrogen heterocycle, see compound 11, potency was retained. The diamine derivatives 21e-g and particularly 35a-c possessing three pharmocophoric groups, that is, the adamantyl and the two amine groups, exhibited high potency. The new compounds did not afford specific activity at non-toxic concentrations against any of the other viruses tested. According to NMR spectroscopy and molecular mechanics calculations it is striking that the parent structures 11 and 27 adopt a fixed trans conformation around C2-C2' bond. In the parent amines, which proved to be active compounds, the distance between nitrogen and adamantyl pharmacophoric groups was different; N-C2' distance is 3.7, 3.8 A for 27, 30 and 2.5 A for 11 suggesting that M2 receptor site can accommodate different in size and orientation lipophilic cages.     

Comparison of Monolisa HCV Ag/Ab ULTRA With Two Anti-HCV Assays For the Detection of HCV Infection in Hospital Setting

In this study, we compared the performance of three serological assays (Monolisa HCV Ag/Ab ULTRA, Innotest HCV Ab IV enzyme immunoassay—EIA, and Ortho HCV 3.0 enzyme-linked immunosorbent assay—ELISA) for the detection of HCV infection. Ninety plasma samples were collected, representing 63 samples from groups at risk for acquiring HCV infection and 27 HCV RNA-positive samples. The results of Ortho HCV 3.0 ELISA, Innotest HCV Ab IV, and Monolisa HCV Ag/Ab ULTRA were fully concordant for 27 HCV RNA-positive samples. Ortho HCV 3.0 ELISA test and Innotest HCV Ab IV also gave the same results for risk groups, while three samples were found to be reactive by Monolisa HCV Ag/Ab ULTRA and were consequently found negative for HCV RNA. As two of the solely Monolisa HCV Ag/Ab ULTRA-positive samples were also hepatitis B s antigen (HBsAg)-positive, neutralization of HBsAg was performed but no arguments for the HBsAg interference were observed. In conclusion, the non-specific reactive signal was observed, in three samples using Monolisa HCV Ag/Ab ULTRA, to be negative by other serological assays, and observed to be negative in an HCV RNA assessment, a result that could not be attributed to the interference with HBsAg. In the context of diagnostic testing, no test for various HCV genotypes was observed to be superior to any other.     

Periodic emission bursts accompanying the interaction of plasma flows propagating across a magnetic field

It is found experimentally that the interaction of plasma flows propagating in opposite directions across a magnetic field is accompanied by periodic local bursts of intense optical and soft X-ray emission. It is shown that periodic variations in the emission intensity from the interaction region are related to the excitation of steady-state self-oscillations in the plasma. By varying the frequency and amplitude of these oscillations, it is possible to satisfy the resonance conditions at certain characteristic plasma frequencies.