Abdominal wall prostheses. Biomechanic and histological study

The best prosthetic material is one which provides the best mechanical resistance with the best biological tolerance. In order to assess the mechanical and histological properties of abdominal wall prostheses, we performed experimental tests in animal models comparing four materials: polypropylene, dacron, polyglactine 910 and a dacron-polyglactine 910 composite. One hundred thirty rabbits were used including 10 controls and 120 test animals. A medial laparotomy was closed with an antemuscular aponevrotic prosthesis in the test animals. Animals were sacrificed at one, two and three months after the operation. Abdominal wall and prosthesis samples were tested to determine resistance to pressure and extension, deformability and elasticity. Histology tests were also done to determine resistance quality and biological tolerance. Dacron was tolerated best and was less resistant than polypropylene, though resistance was satisfactory. There was no advantage with polyglactine compared with non-resorbable prostheses; its only indication would be a septic site. The composite material tested had a resistance comparable with that of dacron but was less well tolerated.     

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.     

Psychosocial characteristics of pregnant and nonpregnant HIV-seropositive women

Thirty-three HIV-positive women, 12 of whom were pregnant, participated in semistructured interviews to define areas of psychosocial need. Eighty-eight percent of the subjects reported current unemployment. A history of substance abuse was reported by 82 percent, suicide attempts by 52 percent, and sexual problems by 43 percent. Approximately 30 percent reported elevated levels of depressive symptoms on standardized symptom inventories. The pregnant women appeared psychologically healthier than the nonpregnant group. HIV-positive women face multiple psychosocial stressors and may experience significant psychological distress.     

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.     

Serotonin and serotonin receptors in the central auditory system

Single channel currents were activated by GABA (0.5 to 5 microM) in cell-attached and inside-out patches from cells in the dentate gyrus of rat hippocampal slices. The currents reversed at the chloride equilibrium potential and were blocked by bicuculline (100 microM). Several different kinds of channel were seen: high conductance and low conductance, rectifying and "nonrectifying." Channels had multiple conductance states. The open probability (Po) of channels was greater at depolarized than at hyperpolarized potentials and the relationship between Po and potential could be fitted with a Boltzmann equation with equivalent valency (z) of 1. The combination of outward rectification and potential-dependent open probability gave very little chloride current at hyperpolarized potentials but steeply increasing current with depolarization, useful properties for a tonic inhibitory mechanism.     

Neutrophil apoptosis is associated with a reduction in CD16 (Fc gamma RIII) expression

Resolution of inflammation involves removal of recruited neutrophils from inflamed sites via a noninflammatory mechanism, possibly involving neutrophil apoptosis and engulfment/phagocytosis by macrophages. In this study, we describe the reduction in surface expression (> 90%) of the neutrophil molecule Fc gamma RIII (CD16) during in vitro culture at 37 degrees C, which was found to be temporally associated with the appearance of neutrophils with apoptotic morphology during in vitro culture and inhibitable by granulocyte-macrophage colony-stimulating factor (GM-CSF), which postpones apoptosis in the neutrophil. By using dual fluorescence analysis, CD16 "low" expressing neutrophils showed reduced staining with the DNA-binding dye propidium iodide, suggesting that CD16 low expressing neutrophils were apoptotic. Separation of CD16 "high" and CD16 "low" expressing neutrophils by fluorescence-activated cell sorting revealed that morphologically apoptotic cells exhibited the CD16 low phenotype. We did not observe similar marked changes in expression of other neutrophil surface molecules (including other phosphatidylinositol (PI)-linked molecules), indicating that generalized loss of surface molecules does not occur during apoptosis. We believe this to be the first reported cell type-specific membrane alteration in a surface glycoprotein associated with apoptosis, suggesting that the program of cell death in the neutrophil, in addition to morphologic and nuclear changes, includes alterations in expression of surface receptors.