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/     

Postcatelectrotonic potentials and trace changes in the nerve fiber excitability

When cathode subthreshold impulse was turned off, excitable membranes of isolated nerve fibres and nervous trunk show postelectrotonic depolarisation (PED), that is a slow recovery of membrane potential to the resting level. PED of the single nodes of Ranvier and nervous trunk is registered not only in normal conditions, but also after complete block of sodium channels. The size and duration of nervous trunk PED under subthreshold depolarising current increase along with duration of applied depolarisation: when cathode current 1 ms in duration was used, they were 0.093 +/- +/- 0.004 mV and 7.123 +/- 0.576 ms, respectively; when current was 5 ms in duration, they were 0.189 +/- 0.005 mV and 23.212 +/- 1.186 ms, whereas a 10-ms depolarisation yields values of 0.220 +/- 0.011 mV and 68.721 +/- 3.389 ms. Application of the train of catelectrotonic impulses leads to PED built-up. As PED is found not only in normal conditions but also after complete block of sodium channels, it is reasonable to suggest that the most probable reason for PED is an outward potassium current.     

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      

Energy analysis of non-covalent ligand binding to nucleic acids: Present and future

Generalization of current views on energy analysis of complex formation of biologically active compounds with nucleic acids is represented and the outlook for further developments is determined.     

Complexation of anthracycline drugs with DNA in the presence of caffeine

The competitive binding of anthracycline antitumour drugs, [daunomycin (DAU), doxorubicin (DOX) or nogalamycin (NOG)], with caffeine (CAF) to a model DNA oligomer has been investigated by 500 MHz ¹H NMR spectroscopy under physiological solution conditions. The method depends on the stepwise analysis of one-component (self-association), two-component (hetero-association and DNA complexation) and three-component interactions, in order to de-convolute the overall binding of the anthracycline antibiotic and CAF to DNA into two competing processes, viz. hetero-association of the antibiotic-CAF (‘interceptor’ action of CAF) and CAF–DNA complexation (‘protector’ action of CAF). It is found that the complexation of DAU with DNA in the presence of CAF is mainly affected by the CAF–DNA complexation, whereas the binding of either DOX or NOG to DNA is affected approximately equally by both the CAF–DNA complexation and CAF-antibiotic hetero-association. Quantitative evaluation of the three-component mixture of drug–CAF–DNA has enabled the proportion of the antibiotic displaced from DNA on addition of CAF to be calculated over a large range of CAF concentration, which may provide a quantitative basis for the change in anthracycline-related toxicity on addition of CAF.