Duration of spinal anaesthesia is determined by the partition coefficient of local anaesthetic

We have compared the duration of motor block produced by four local anaesthetics administered into a chronically implanted subarachnoid catheter in rabbits. Each group (n = 6) received four different doses of amethocaine, bupivacaine, lignocaine or procaine, and the duration of the resulting motor block was assessed. Dose-response curves were plotted for each drug. As a measure of activity of the anaesthetics, we used the dose of each drug required to produce block of 60-min duration (D60 min) and the correlation between D60 min and different drug properties was examined. An inverse linear correlation (r = 0.995; P < 0.01) was observed between log D60 min and the log of the partition coefficient of the local anaesthetics. No correlation was found between the effect and degree of protein binding, pKa or molecular weight. These results suggest that, in spinal anaesthesia, the partition coefficient could be used as a predictor of the duration of anaesthetic action.     

To Be or Not to Be Electronic Money, That's the Question

The European Electronic Money Directive contains a definition of electronic money. However, determining which systems involving the use of electronic value fall under its scope can be more complicated than one might think. This issue is explored in this article through consideration of the question of whether prepaid mobile phone credits qualify as electronic money—a question that is currently being debated by telecommunications operators and regulators.     

The absolute number of trans-rearrangements between the TCRG and TCRB loci is predictive of lymphoma risk: a severe combined immune deficiency (SCID) murine model

Pilot studies in human populations have demonstrated a correlation between the level of antigen receptor trans-rearrangements and risk (at the population level) of lymphoid malignancy. Irradiation of newborn severe combined immune deficiency mice results in an increased risk of subsequent development of thymic lymphoma (100% of mice so irradiated are dead of thymic lymphoma by 20 weeks of age). We, therefore, assayed the occurrence of trans-rearrangements in this well-controlled mouse mutant system and found a 50-100-fold increase in the absolute number of TCRGV-TCRBJ trans-rearrangements compared to unirradiated littermates (and a comparable fold increase over age-matched BALB/c mice) at 2 weeks following irradiation. We also found a marked disproportion in generating trans-rearrangements versus intralocus rearrangements in the severe combined immune deficiency system compared to BALB/c, independent of irradiation. The trans-rearrangements noted were polyclonal in nature. These data, again, suggest that the absolute level of antigen receptor trans-rearrangements may serve as a biomarker of lymphoma risk.     

Random sequence multisets for synchronous code-divisionmultiple-access channels

The effect of using randomly selected sequence multisets for the uplink of a synchronous code-division multiple-access channel is considered. A tight lower bound on the expected value of the sum capacity over the ensemble of randomly selected sequence multisets is given. For large systems, the sum rate penalty for using randomly selected multisets is shown to be at most 1 nat and to vanish as the number of users becomes large, compared to the sequence length     

A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides

During the last decade, episodes of sepsis have increased and Escherichia coli has remained the most frequent clinical isolate. Lipopolysaccharides (LPS; endotoxin) are the major toxic and antigenic components of gram-negative bacteria and qualify as targets for therapeutic interventions. Molecules that neutralize the toxic effects of LPS are actively investigated. In this paper, we describe a murine monoclonal antibody (MAb; WN1 222-5), broadly cross-reactive and cross-protective for smooth (S)-form and rough (R)-form LPS. As shown in enzyme-linked immunosorbent assay and the passive hemolysis assay, WN1 222-5 binds to the five known E. coli core chemotypes, to Salmonella core, and to S-form LPS having these core structures. In immunoblots, it is shown to react with both the nonsubstituted core LPS and with LPS carrying O-side chains, indicating the exposure of the epitope in both S-form and R-form LPS. This MAb of the immunoglobulin G2a class is not lipid A reactive but binds to E. coli J5, an RcP+ mutant which carries an inner core structure common to many members of the family Enterobacteriaceae. Phosphate groups present in the inner core contribute to the epitope but are not essential for the binding of WN1 222-5 to complete core LPS. Cross-reactivity for clinical bacterial isolates is broad. WN1 222-5 binds to all E. coli clinical isolates tested so far (79 blood isolates, 80 urinary isolates, and 21 fecal isolates) and to some Citrobacter, Enterobacter, and Klebsiella isolates. This pattern of reactivity indicates that its binding epitope is widespread among members of the Enterobacteriaceae. WN1 222-5 exhibits biologically relevant activities. In vitro, it inhibits the Limulus amoebocyte lysate assay activity of S-form and R-form LPS in a dose-dependent manner and it neutralizes the LPS-induced release of clinically relevant monokines (interleukin 6 and tumor necrosis factor). In vivo, WN1 222-5 blocks endotoxin-induced pyrogenicity in rabbits and lethality in galactosamine-sensitized mice. The discovery of WN1 222-5 settles the long-lasting controversy over the existence of anti-core LPS MAbs with both cross-reactive and cross-protective activity, opening new possibilities for the immunotherapy of sepsis caused by gram-negative bacteria.     

Synthesis and cytotoxicity of potential tumor-inhibitory analogues of trimelamol (2,4,6-tris[(hydroxymethyl)methylamino]-1,3,5-triazine) having electron-withdrawing groups in place of methyl

In exploring the structural features which determine the antitumor activity of 2,4,6-tris-[(hydroxymethyl)methylamino]-1,3,5-triazine (trimelamol, 1), we have synthesized analogues in which the methyl groups have been replaced by the electron-withdrawing substituents 2,2,2-trifluoroethyl (5), propargyl (13), and cyanomethyl (15) via the respective tris(alkylamino)triazines 3, 12, and 14. Three mono[(hydroxymethyl)amino]triazines (4, 7, and 10) were also prepared. All the new tris(hydroxymethyl) derivatives showed cytotoxicities toward a variety of experimental rodent and human ovarian tumor cell lines similar to those shown by 1, the cyanomethyl analogue (15) having the most favorable profile. Mono(hydroxymethyl) derivatives (4 and 7) were ca. one-third as toxic. The new tris(hydroxymethyl) analogues were more stable to aqueous hydrolysis than was 1. Half-life (pH 7.5) values were, for 1, 120 min, for 5, 690 min, for 13, 450 min, and for 15, 275 min, but at pH 2.0, 15 (t1/2 350 min) was the most stable. This cyanomethyl analogue was also the most water-soluble, being comparable to 1 whereas 5 and 13 were poorly soluble.     

Sexual dimorphism of circulating somatotropin, insulin-like growth factor I and II, insulin-like growth factor binding proteins, and insulin: relationships to growth rate and carcass characteristics in growing lambs

The effects of sex and age on patterns of circulating somatotropin (ST) concentration and plasma IGF-I, IGF-II, insulin, and IGF binding protein-3 (IGFBP-3) were studied in ram, wether, and ewe lambs (n = 7 or 8) sampled at mean ages of 81 (I1) and 158 d (I2). Between 81 and 158 d of age, rams grew more rapidly than wethers (P < .01), and wethers grew more rapidly than ewes (P < .01). The sex differences in growth were reflected in empty body weight at slaughter: rams > wethers > ewes (P < .05). Mean plasma ST concentrations, ST pulse amplitude, and integrated plasma ST concentrations were greater (P < .05) in rams than in ewes at I1 and I2. Characteristics of the ST plasma profile in wethers were generally intermediate between those of rams and ewes. The interpulse interval was greater in ewes than in wethers at I2. The IGF-I and IGFBP-3 concentrations were greater in rams than in ewes at both sampling times. Plasma IGF-II was greater in ewes than in rams at I2. Mean plasma ST was approximately two thirds less at I2 than at I1 regardless of sex. Mean plasma ST and IGF-I at both ages were positively correlated with growth. Mean plasma ST at I2 was negatively correlated with fatness at slaughter. Sex and age significantly affected patterns of circulating ST and concentrations of IGF-I and IGFBP-3 in prepubertal growing lambs, under conditions for which growth rates and composition were also sexually dimorphic.     

Development and simulation studies of an unsteady state biofilter model for the treatment of cyclic air emissions of an α‐pinene gas stream

This paper describes the development and simulation of an unsteady state biofilter model used to predict dynamic behaviour of cyclically‐operated biofilters and compares it with experimental results obtained from three, parallel, bench‐scale biofilters treating both periodically fluctuating concentrations and constant concentrations of an α‐pinene‐laden gas stream. The dynamic model, using kinetic parameters estimated from the constant concentration biofilter, was able to predict the performance of cyclic biofilters operating at short cycle periods (ie, in the order of minutes and hours). Steady state kinetic data from a constant concentration biofilter can be used to predict unsteady state biofilter operation. At a 24 h cycle period, the dynamic model compared well with experimental results. For long cycle periods (ie, hours and days), removal efficiency decreased after periods of non‐loading: the longer the period of non‐loading, the poorer the biofilter's performance at the re‐commencement of pollutant loading. At longer time scales the model did not effectively predict transient behaviour, as adsorption and changes in kinetic parameters were not accounted for. Modelling results showed that similar biofiltration performance for the cyclic and constant concentration biofiltration of α‐pinene is expected for biofilters operating solely in the first order kinetics regime. Poorer performance for cyclic biofilters following Monod kinetics spanning the entire kinetics range is expected as the cycle amplitude increases. The most important parameters affecting the performance of a cyclically‐operated biofilter with short cycle periods are: amplitude of cyclic fluctuations, C_{g, max}/C_g, relative value of the half‐saturation constant in the Monod expression, K_s, and effective diffusivity of α‐pinene in the biofilm, D_e. Copyright © 2005 Society of Chemical Industry     

The reporting of the risks from genetically modified organisms in the mass media, 2002–2004

This paper describes an analysis of coverage of the risks from agricultural and food genetically-modified organisms (GMOs) from April 2002 to April 2004 in 14 news media from six countries (Canada, France, Germany, Spain, the UK and the USA) which was conducted as part of a review for the European Commission of the management of risk communication. A total of 597 relevant news articles were found and coded for their presentational tone, the types of risk (environmental, financial, health and political, in that order), the organisms described (mainly maize, rape and beet crops), and the documents, people and organisations cited. UK news media tended to be the most “scary” and Spanish ones the most “robust”. Articles quoting public perceptions, non-governmental environmental organisations and politicians tended to emphasize the risks of GMOs; those quoting scientists tended to downplay the risks and describe their potential benefits. Some suggestions for possible action by the European Commission are put forward, such as the facilitation of contact between journalists and scientists, but it is recognized that for some newspapers, their editorial wish to campaign will inevitably over-ride their reporters’ wish to present the truth.