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/     

Origin of bilateral-symmetrical animals (Bilateria)

The paper is an attempt to attack the old problem of the origin of Bilateria by the methods of evolutionary tetrad (i.e. combination of comparative anatomy, comparative embryology, paleontology, and molecular biology). Three groups of theories of classical comparative anatomy (planulod-turbellarian, archicoelomate, and metameric) are discussed. Comparative embryology brings out clearly that the ventral side of embryo comes from the blastoporal region in all groups of Bilateria (except Chordata, where the blastoporal region corresponds to the dorsal side that is come out of the upside-down morphology of chordates) and mouth and anus comes from the anterior and posterior ends of elongated blastopore. From the point of view of paleontology, some of vendian metazoans demonstrate transitional conditions between the Radiata and Bilateria. Vendian bilaterians are metameric organisms with normal or asymmetric position of segments and could be pictured as "bilateral coelenterates" creeping on the oral surface. In Cnidaria, the expression of homologues of "Brachyury", "goosecoid", and "fork head" genes are revealed in the circular region around the mouth. In Bilateria, these genes are expressed along the elongated blastopore and around the mouth and anus. These results support the old conception on the amphistomic origin of mouth and anus as well as the homology between the oral disc of cnidarians and ventral side of Bilateria. The combination of four mentioned approaches enables us to propose the conception of the origin of Bilateria from vendian bilateral coelenterates with numerous metameric pouches of gastral cavity. Bilaterian ancestors crawled on the oral disc (= ventral side). These ancestors gave rise to both phanerosoic cnidarians and triploblastic bilaterians. Cnidarian ancestors attached to bottom by the aboral pole with the resulting degradation of aboral nerve ganglion. Bilateral symmetry of anthozoans is considered to be primitive feature for cnidarians. In case of triploblastic Bilateria, the elongated blastopore closed in the middle and subdivided into mouth and anus (amphistomy) and gastral pouches separated from the central part of gastral cavity and transformed to metameric coelomic chambers. The primary bilaterians are supposed to be complicated organisms having coelom and segmentation. The complexity of primary Bilateria provides an explanation for the abundance of highly organized organisms (arthropods, mollusks etc.) in Cambrian time. It is postulated that Ctenophora is the only group recent eumetazoans with primary axial symmetry.     

Symmetry of priapulids (Priapulida). 2. Symmetry of larvae

Larvae of priapulids are characterized by radial symmetry evident from both external and internal characters of the introvert and lorica. The bilaterality appears as a result of a combination of several radial symmetries: pentaradial symmetry of the teeth, octaradial symmetry of the primary scalids, 25-radial symmetry of scalids, biradial symmetry of the neck, and biradial and decaradial symmetry of the trunk. Internal radiality is exhibited by musculature and the circumpharyngeal nerve ring. Internal bilaterality is evident from the position of the ventral nerve cord and excretory elements. Externally, the bilaterality is determined by the position of the anal tubulus and two shortened midventral rows of scalids bordering the ventral nerve cord. The lorical elements define the biradial symmetry that is missing in adult priapulids. The radial symmetry of larvae is a secondary appearance considered an evolutionary adaptation to a lifestyle within the three-dimensional environment of the benthic sediment.     

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      

Study of plasma confinement in the L-2M stellarator during the formation of an edge transport barrier

A plasma confinement mode characterized by the formation of an edge transport barrier (ETB) was discovered in the L-2M stellarator after boronization of the vacuum vessel wall. The transition into this mode is accompanied by a jump in the electron temperature by 100–200 eV at the plasma edge and a sharp increase in the gradient of the electron temperature T _e in this region. The threshold power for the transition into the ETB confinement mode with an increased electron temperature gradient is P _thr ^?Te = (60 ± 15)n _e [10¹⁹ m^?3] kW. The formation of the ETB manifests itself also in a substantial change in the electron density profile. A density peak with a steep gradient at the outer side forms at the plasma edge. The threshold power for the transition into the ETB confinement mode corresponding to a substantial increase in the plasma density gradient near r = a is P _thr ^?Te = (67 ± 9)n _e [10¹⁹ m^?3] kW, which agrees to within experimental error with the threshold power for the transition into the ETB confinement mode determined from the sharp increase in the gradient of the electron temperature T _e . The value of P _thr for the L-2M stellarator agrees to within 25% with that obtained from the tokamak scaling. In the ETB confinement mode, the plasma energy W and the energy confinement time τ _E determined from diamagnetic measurements increase by 20–30% as compared to those obtained from the stellarator scaling for the confinement mode without an ETB. When the heating power increases by a factor of 2–3 above the threshold value, the effects related to improved energy confinement disappear.