Histological and biomechanical analysis of bone and interface reactions around hydroxyapatite-coated intramedullary implants of different stiffness: a pilot study on the goat

We hypothesized that reduced stem stiffness of orthopaedic implants contributes to a high risk of loosening, since interface stresses and relative motions may exceed a tolerable range. To study this hypothesis, three types of load-bearing implant with different stiffnesses were inserted into the tibia of the goat. Histological analysis was performed of bone repair after insertion of the implant, bone ingrowth, interface disruption and loosening. A finite element model of the configuration provided the quantitative range of interface stresses and relative motions for the present experiment. The implants were made out of stainless steel, hollow titanium and a thin titanium core covered with a polyacetal coating. The stiffness ratios of these implants were approximately 10:4:1, respectively. All implants were coated with a layer of hydroxyapatite (HA) in order to minimize the possible biological effects of the different implant materials. Irrespective of the type of implant, there was a repair phase that lasted 6-12 weeks. The stiff implants functioned well. Large areas of bone bonding to the HA layer were found after the repair phase at 12 weeks postoperatively. After 24 weeks, some signs of loosening were observed. More loosening occurred with the hollow titanium and polyacetal implants, mainly during the repair phase. Three hollow titanium and three polyacetal coated implants survived this period, and were killed after 24 weeks. The integrity of the HA layer at the bone-implant interface of the titanium implants was good. In the polyacetal implants, the repair reaction of the cortical bone was incomplete. Bone ingrowth into HA was largely lacking. In conclusion, we found significant differences in the repair and interface reactions around implants of different stiffness. Stiff implants showed favourable initial interface conditions for bone ingrowth. Intermediate and flexible implants provoked unfavourable interface conditions for initial bone ingrowth. The finite element study showed that the flexible stems produce larger micromotions and higher interface stresses at the bone-prosthesis interface than the stiff stems, indicating an explanation for the histological findings.     

A hermeneutic analysis of the process of conducting clinical interviews

1. Although no right way to interview exists, an interviewer should develop a comfortable, personal style. 2. Allowing an interview to follow its own course while remembering the overall interview agenda will contribute to quality of the data. 3. Interviewing skills are enhanced as the interviewer develops a personal style and becomes comfortable as a practitioner.     

Increased response/recovery lifetimes and reinforcement of polyaniline nanofiber films using carbon nanotubes

We have prepared high surface area, conductive, mechanically robust, responsive polyaniline–carbon nanotube composite films. These were produced by filtration from dilute dispersions of polyaniline nanofibers and single-walled carbon nanotubes. Unlike polyaniline alone, these composites are mechanically stable, maintain large intractable surfaces and exhibit greatly enhanced response/recovery behavior to changes in their local environment. This is illustrated by exposing the films to ammonia.     

Enhancing the carbon sink in European agricultural soils: including trace gas fluxes in estimates of carbon mitigation potential

The possibility that the carbon sink in agricultural soils can be enhanced has taken on great political significance since the Kyoto Protocol was finalised in December 1997. The Kyoto Protocol allows carbon emissions to be offset by demonstrable removal of carbon from the atmosphere. Thus, forestry activities (Article 3.3) and changes in the use of agricultural soils (Article 3.4) that are shown to reduce atmospheric CO₂levels may be included in the Kyoto emission reduction targets. The European Union is committed to a reduction in CO₂ emissions to 92% of baseline (1990) levels during the first commitment period (2008–2012). We have shown recently that there are a number of agricultural land-management changes that show some potential to increase the carbon sink in agricultural soils and others that allow alternative forms of carbon mitigation (i.e. through fossil fuel substitution), but the options differ greatly in their potential for carbon mitigation. The changes examined were, (a) switching all animal manure use to arable land, (b) applying all sewage sludge to arable land, (c) incorporating all surplus cereal straw, (d) conversion to no-till agriculture, (e) use of surplus arable land to de-intensify 1/3 of current intensive crop production (through use of 1/3 grass/arable rotations), (f) use of surplus arable land to allow natural woodland regeneration, and (g) use of surplus arable land for bioenergy crop production. In this paper, we attempt for the first time to assess other (non-CO₂) effects of these land-management changes on (a) the emission of the other important agricultural greenhouse gases, methane and nitrous oxide, and (b) other aspects of the ecology of the agroecosystems. We find that the relative importance of trace gas fluxes varies enormously among the scenarios. In some such as the sewage sludge, woodland regeneration and bioenergy production scenarios, the inclusion of trace gases makes only a small (<10%) difference to the CO₂-C mitigation potential. In other cases, for example the no-till, animal manure and agricultural de-intensification scenarios, trace gases have a large impact, sometimes halving or more than doubling the CO₂-C mitigation potential. The scenarios showing the greatest increase when including trace gases are those in which manure management changes significantly. In the one scenario (no-till) where the carbon mitigation potential was reduced greatly, a small increase in methane oxidation was outweighed by a sharp increase in N₂O emissions. When these land-management options are combined to examine the whole agricultural land area of Europe, most of the changes in mitigation potential are small, but depending upon assumptions for the animal manure scenario, the total mitigation potential either increases by about 20% or decreases by about 10%, shifting the mitigation potential of the scenario from just above the EU's 8% Kyoto emission reduction target (98.9 Tg C y⁻¹) to just below it. Our results suggest that (a) trace gas fluxes may change the mitigation potential of a land management option significantly and should always be considered alongside CO₂-C mitigation potentials and (b) agricultural management options show considerable potential for carbon mitigation even after accounting for trace gas fluxes. This revised version was published online in August 2006 with corrections to the Cover Date.     

Structural and functional analogy between pneumolysin and proaerolysin

Pneumolysin and proaerolysin are bacterial toxins that form pores in host cells by oligomerization. We propose that they may have similar structures despite a poor sequence identity. The crystal structure of proaerolysin reveals a protein composed of four domains, arranged in the shape of an elongated comma. Electron microscopy of the pneumolysin monomer shows a similar arrangement of domains. The sequence of pneumolysin recognizes the template of proaerolysin from a library of protein folds. A three-dimensional model of pneumolysin has been constructed by the comparative approach using the structure of proaerolysin. This model, together with results on the activity of site- specific mutants and the positions of antigenic sites, has been used to propose functional roles of individual domains.      

Production of human normal adult and fetal hemoglobins in Escherichia coli

A hemoglobin expression system in Escherichia coli is described. In order to produce authentic human hemoglobin, we need to co-express both methionine aminopeptidase and globin genes under the control of a strong promoter. We have constructed three plasmids, pHE2, pHE4 and pHE7, for the expression of human normal adult hemoglobin and a plasmid, pHE9, for the expression of human fetal hemoglobin, in high yields. The globin genes can be derived from either synthetic genes or human globin cDNAs. The extra amino-terminal methionine residues of the expressed globins can be removed by the co-expressed methionine aminopeptidase. The heme is inserted correctly into the expressed alpha- globin from our expression plasmids. A fraction (approximately 25%) of the heme is not inserted correctly into the expressed beta- or gamma- globin. However, the incorrectly inserted hemes can be converted into the correct conformation by carrying out a simple oxidation-reduction process on the purified hemoglobin molecule. We have investigated the functional properties of the expressed hemoglobins by measuring their oxygen-binding properties and their structural features by obtaining their 1H-NMR spectra. Our results show that authentic human normal adult and fetal hemoglobins can be produced from our expression plasmids in E. coli and in high yields. Our expression system allows us to design and to produce any recombinant hemoglobins needed for our research on the structure-function relationship in hemoglobin.      

Impact of H+ ion irradiation on Matrimid®. I. Evolution in chemical structure

Ion beam irradiation can be used to modify the structure and gas transport properties of glassy polymers. This is the first of two studies that focus on the impact of H⁺ ion irradiation on the structure and permeation properties of the polyimide Matrimid®. Specifically, the evolution in chemical structure after H⁺ irradiation over a range of fluences was analyzed using FTIR spectroscopy and dissolution studies. Although H⁺ ion irradiation at very low ion fluences induced little modification in the chemical structure, irradiation at relatively high ion fluences resulted in crosslinking of the irradiated films. The branched structure of the aliphatic methyl (CH₃) was the most sensitive to the H⁺ ion irradiation. The para‐disubstituted aromatic ring showed the strongest resistance toward ion irradiation and required fairly high doses to induce degradation. Two potential crosslinking mechanisms related to the degradation of the aliphatic methyl and the benzophenone carbonyl were presented. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 2010–2019, 2003     

Discovery of a Potent,CNS‐Penetrant Orexin Receptor Antagonist Based on an N,N‐Disubstituted‐1,4‐diazepane Scaffold that Promotes Sleep in Rats

Silent Night : Antagonism of the orexin (or hypocretin) system has recently been identified as a novel mechanism for the treatment of insomnia. Herein, we describe discovery of a dual (OX₁R/OX₂R) orexin receptor antagonist featuring a 1,4‐diazepane central constraint that blocks orexin signaling in vivo. In telemetry‐implanted rats, oral administration of this antagonist produced a decrease in wakefulness, while increasing REM and non‐REM sleep.