Where should health services go: local authorities versus the NHS?

The Association of Metropolitan Authorities has recently proposed that responsibility for the NHS should pass from health authorities to local authorities. One of the fiercest debates at the outset of the NHS was whether the hospitals should be run by local authorities. In the end the minister for health, Aneurin Bevan, decided against local democracy and in favour of a national health service. His arguments included the fact that equality of treatment could not be guaranteed if facilities varied with local finances and that even the largest authorities were not big enough to pool risks and expertise. All these arguments still apply today, and the recent changes in community care provide an insight into how a market model of local authority control might work. The changes have been accompanied by a shift from public to private sector provision and the introduction of charges for services that the NHS once provided free. As important, the willingness and ability of local authorities to raise extra revenue from local taxes and charges affect the service they can provide, so leading to inequalities of provision. Local authorities have yet to make the case that they can preserve the fundamental principles and benefits of the NHS, including its reliance on central taxation and unified funding formulas.     

Comparison of protein adsorption isotherms and uptake rates in preparative cation-exchange materials

Adsorption isotherms and effective diffusivities of lysozyme in a set of six preparative cation-exchange stationary phases were determined from batch uptake data in a stirred vessel. Both a pore diffusion and a homogeneous diffusion model were used in estimating diffusivities, with the isotherms fitted to a non-Langmuirian analytical isotherm equation. The capacities inferred from the isotherms are found to be correlated with the surface area accessible to lysozyme, the effective surface concentrations obtained being in agreement with values measured by different methods in various non-chromatographic systems. The pore diffusivities show systematic trends with protein and salt concentration, and effects of pore size and connectivity are also evident. Some trends in the homogeneous diffusivities are quite different to those in the pore diffusivities, but these differences largely disappear when the homogeneous diffusivities are rescaled to account for adsorption equilibrium behavior. Additional information is required to elucidate further the mechanisms of coupled diffusion and adsorption in stationary phases.     

Experimental study of the interaction range and association rate of surface-attached cadherin 11

We describe a method allowing quantitative determination of the interaction range and association rate of individual surface-attached molecules. Spherical beads (1.4 micro(m) radius) were coated with recombinant outer domains of the newly described classical type II cadherin 11, a cell adhesion molecule. Beads were driven along cadherin-coated surfaces with a hydrodynamic force of approximately 1 pN, i.e., much less than the mechanical strength of many ligand-receptor bonds. Spheres displayed periods of slow motion interspersed with arrests of various duration. Particle position was monitored with 50 Hz frequency and 0.025 micro(m) accuracy. Nearly 1 million positions were recorded and processed. Comparison between experimental and computer-simulated trajectories suggested that velocity fluctuations might be related quantitatively to Brownian motion perpendicular to the surface. The expected amplitude of this motion was of order of 100 nm. Theoretical analysis of the relationship between sphere acceleration and velocity allowed simultaneous determination of the wall shear rate and van der Waals attraction between spheres and surface. The Hamaker constant was estimated at 2.9 x 10(-23) J. The frequency of bond formation was then determined as a function of sphere velocity. Experimental data were consistent with the view that the rate of association between a pair of adhesion molecules was approximately 1.2 x 10(-3) s-1 and the interaction range was approximately 10 nm. It is concluded that the presented methodology allows sensitive measurement of sphere-to-surface interactions (with approximately 10 fN sensitivity) as well as the effective range and rate of bond formation between individual adhesion molecules.     

The detection of oligonucleotide N3'-->P5' phosphoramidate/RNA duplexes with capillary gel electrophoresis

Oligonucleotide N3'-->P5' phosphoramidates (3'-phosphoramidates) are DNA analogs that are presently under investigation as potential therapeutic agents. These compounds may also hold promise as a diagnostic tool. Here, we describe a rapid method for the analysis of single-stranded RNA fragments utilizing 3'-phosphoramidate oligonucleotides as probes in conjunction with capillary gel electrophoresis (CGE). 3'-Phosphoramidate 9-mers were mixed with complimentary RNA, and CGE was used to monitor duplex formation. Complimentary strands of RNA and 3'-phosphoramidate formed duplexes that gave unique relative mobilities based on an internal standard. The ability of CGE to discriminate between perfect duplexes and duplexes that contain a base mismatch was also investigated. However, the primary focus of this work was to determine CGE's ability to detect the presence of the 3'-phosphoramidates/RNA duplex under routine electrophoretic running conditions. Polyacrylamide gel electrophoresis analysis was utilized to verify duplex formation.     

Effects of surgery on the pharmacokinetic parameters of drugs

As with other forms of stress, surgery is a time of fluctuating haemodynamics, physiological shifts, intense metabolic changes, and protein catabolism and anabolism. At times, these changes can occur within hours. There is a reasonable body of literature concerning the adverse effects of surgery on gastric emptying, but not on the effects of surgery on the distribution, metabolism and excretion of drugs. Gastric emptying is diminished or absent following major procedures, which prevent the delivery of orally administered drugs to their major site of absorption, the small bowel. Changes in the paracellular absorption of drugs may occur postoperatively, although transcellular absorption appears to be unimpaired. Distribution is affected by changes in blood volume, alterations in circulation, increases in the extracellular fluid and changes in the circulating plasma protein levels, such as albumin and alpha 1-acid glycoprotein. Little is known about alterations in drug metabolism following surgery. However, it has been shown that systemic hypoxia alters the function of some of the cytochrome P450 (CYP) system and increased levels of cytokines have an effect on the metabolism of at least 1 drug. In addition, the renal elimination of drugs is affected in patients postoperatively, although the effects of biliary clearance in this period are difficult to determine. Despite the lack of research into pharmacokinetics during the postoperative period, and given the immense and often sudden changes observed in patients post-surgery, it is reasonable to recommend vigilance with respect to drug therapy during this period.     

A dilatometer for measuring autogenous deformation in hardening portland cement paste

Different techniques for measuring autogenous deformation in cement paste are discussed, and a newly developed dilatometer designed specially for measuring this deformation is described. A particular characteristic of the dilatometer is the encapsulation of the cement paste in corrugated moulds. This restricts moisture loss and ensures that the hardening cement paste suffers insignificant restraint. In addition, the encapsulation permits measurements to commence shortly after casting.     

Characteristics of the lipase from the mold,Geotrichum candidum: A review

The moldGeotrichum candidum produces an extracellular lipase, readily concentrated by removal of the culture medium in which the microorganism is grown. The lipase is characterized by a unique, but not absolute, specificity for fatty acids containingcis-9 orcis,cis-9, 12 unsaturation, hydrolyzing both regardless of position within the triglyceride molecule. The enzyme also hydrolyzescis-9-16∶1,cis,trans-9,12-18∶2,trans,cis-9,12-18∶2, palmitoyl oleate and cholesteryl oleate. Digested at comparatively slow rates are:trans,trans-9,12-18∶2, double bond positional isomers of 18∶1 (other thancis-9), stearolic acid, oleoylpalmitate, dilinoleoyl phosphatidyl choline, and saturated acids. The enzyme has an optimum pH of 8.2, and the lyophilized powder is extremely stable, retaining activity for at least eight years when stored at-20 C. A purification of 81-fold has been achieved. One of five papers presented in the Symposium “Microbial Lipolytic Enzymes,” AOCS Spring Meeting, New Orleans, April 1973. Scientific contribution 556, Agricultural Experiment Station, University of Connecticut, Storrs, Conn. 06268.     

Lipolysis of trivernolin by pancreatic lipase

Vernolic acid (cis-12,13-epoxy-cis-9-oetadece-noic acid) occurs as the triglyceride in the seed ofVernonia anthelmintica. Incubation of the seed produces a 1,3-divernolin. To determine whether the structure of trivernolin is responsible for the apparent secondary ester position specificity of the natural enzyme, trivernolin and tri-olein, were incubated with pancreatic lipase and the free fatty acids and monoglycerides were determined after 5 and 15 min digestion periods. The preponderance of 2-monoglyceride produced by the action of pancreatic lipase was interpreted to indicate that the structure of trivernolin was not solely responsible for the secondary position specificity of theV. anthelmintica lipase toward trivernolin.     

Creating geometrically robust designs for highly sensitive problems using topology optimization

Resonance and wave-propagation problems are known to be highly sensitive towards parameter variations. This paper discusses topology optimization formulations for creating designs that perform robustly under spatial variations for acoustic cavity problems. For several structural problems, robust topology optimization methods have already proven their worth. However, it is shown that direct application of such methods is not suitable for the acoustic problem under consideration. A new double filter approach is suggested which makes robust optimization for spatial variations possible. Its effect and limitations are discussed. In addition, a known explicit penalization approach is considered for comparison. For near-uniform spatial variations it is shown that highly robust designs can be obtained using the double filter approach. It is finally demonstrated that taking non-uniform variations into account further improves the robustness of the designs.