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Biomedical subjects

P A Goddard

Publications and source records attributed to P A Goddard.

13 recordsLinked to original sources

Catastrophic Fermi surface reconstruction in the shape-memory alloy AuZn.

AuZn undergoes a shape-memory transition at 67 K. The de Haas-van Alphen effect persists to 100 K enabling the observation of a change in the quantum oscillation spectrum indicative of a catastrophic Fermi surface reconstruction at the transition. The coexistence of both Fermi surfaces at low temperatures suggests an intrinsic phase separation in the bulk of the material. In addition, Dingle analysis reveals a sharp change in the scattering mechanism at a threshold cyclotron radius, attributable to the underlying microstructure driving the shape-memory effect.

Journal Article↗

Landau quantization effects in the charge-density-wave system (Per)2M(mnt)2 (where M = Au and Pt).

A finite transfer integral t(a) orthogonal to the conducting chains of a highly one-dimensional metal gives rise to empty and filled bands that simulate an indirect-gap semiconductor upon formation of a charge-density wave (CDW). In contrast to semiconductors such as Ge and Si with band gaps approximately 1 eV, the CDW system possesses an indirect gap with a greatly reduced energy scale, enabling moderate laboratory magnetic fields to have a major effect. The consequent variation of the thermodynamic gap with magnetic field due to Zeeman splitting and Landau quantization enables the electronic band structure parameters (transfer integrals, Fermi velocity) to be determined accurately. These parameters reveal the orbital quantization limit to be reached at approximately 20 T in (Per)2M(mnt)(2) salts, making them highly unlikely candidates for a recently proposed cascade of field-induced CDW states.

Journal Article↗

Comparison of two in vivo and two ex vivo tests to assess the antibacterial activity of several antiseptics.

An ex vivo test was adapted to mimic the in vivo conditions of testing antiseptic activity on human forearms and in the European Standard Hygienic Handwash Test (BSEN 1499). The study was to validate the ex vivo protocols using 4.8% (w/v) para-chloro-meta-xylenol (PCMX, neat Dettol), 0.5% (w/v) triclosan in 70% (v/v) isopropanol, and 2% (v/v) povidone-iodine against a high bacterial inoculum (>10(8) cfu/mL) of Escherichia coli NCTC 10538. Two ex vivo tests using human skin samples, including one introducing a mechanical rubbing effect, were compared with two corresponding in vivo tests (the forearm test and the BSEN handwashing test). All antiseptics assessed in vivo (forearm and handwash tests) produced reductions in bacterial counts that were significantly greater than those for the non-medicated soft soap control. When assessed ex vivo without rubbing, only PCMX and povidone-iodine achieved reductions significantly greater than soft soap. When assessed ex vivo with mechanical rubbing, only PCMX and triclosan achieved reductions significantly greater than soft soap. Overall, the antiseptics at the concentrations tested were more active when tested in vivo than ex vivo. The addition of a mechanical effect, either in vivo by the volunteers washing their hands or ex vivo by a drill rubbing two skin samples against each other, produced a significantly greater reduction in bacterial concentrations. The ex vivo tests were easily adapted to mimic in vivo protocols. The value of such tests, particularly the one that includes a rubbing effect, may be significant as they avoid the need for human volunteers.

Adolescent↗

Use of the 'ex vivo' test to study long-term bacterial survival on human skin and their sensitivity to antisepsis.

AIMS: To determine bacterial survival on human skin and their sensitivity to antisepsis. METHODS AND RESULTS: An 'ex vivo' protocol which uses human skin samples placed into diffusion cells, and electron microscopy (EM), were used to study the growth of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa inoculated onto skin samples over a 46-h incubation period at 32 degrees C. Concurrently variation in skin pH was evaluated at different time intervals during this period. In addition the antimicrobial activity of three antiseptics against the incubated micro-organisms was assessed quantitatively with the 'ex vivo' test, while their detrimental effects against bacteria were observed by EM. All three bacteria were still present in high number after 46 h inoculation on skin, although the concentration of E. coli and S. aureus were reduced by 2.74 and 1.58 log(10) reduction, respectively, over this period of time. Electron micrographs showed clear evidence of cell division and some bacteria appeared to be embedded into the skin layers. The antiseptics tested had some antibacterial activity against bacteria incubated on skin for 3 and 10 h, and EM evidence showed some morphological damages including cellular blebbing and the presence of fibrillar material around the cells. All micro-organisms had an acidifying effect on skin samples. CONCLUSIONS: Here, it was shown that bacterial pathogens can survive and grow when incubated on human skin. In addition, it is possible that they can penetrate the stratum corneum, which can provide some protection against antisepsis. SIGNIFICANCE AND IMPACT OF THE STUDY: The apparent low bactericidal activity of biocides attributed in part to bacterial protection from skin layers is particularly important to assess in order to ensure antisepsis efficacy.

2-Propanol↗

Assessment of skin viability: is it necessary to use different methodologies?

BACKGROUND/AIM: Skin is complex and may display variable structural and metabolic change 'ex vivo'. The present study aimed to follow measures of skin viability and evaluate their usefulness as markers of viability. MATERIALS AND METHODS: We evaluated the viability of skin samples fresh or after being frozen and subsequently thawed. Assessments included histopathological appearance, lactate dehydrogenase (LDH) activity, oxygen consumption and skin pH. RESULTS: Morphological investigations of fresh and frozen skin samples using light and electron microscopy showed samples with relatively well-defined epidermis and dermis. Frozen samples showed some sign of stratum corneum fragmentation, although this was not obvious. LDH activity measured in fresh samples kept at 4 degrees C was low, but it was stable up to 7 days. Fresh samples kept at 32 degrees C had a comparable LDH activity to the ones kept in the fridge up to 4 days. Frozen samples, thawed and then kept at 4 degrees C showed a stable LDH activity after 24 h of incubation. However, frozen samples incubated at 32 degrees C demonstrated a high variability in results, with up to 800 U/L of LDH activity after 5 days of incubation. Freshly excised as well as freshly thawed samples showed the highest respiration rates. Fresh and thawed samples stored for a long period of time had a significantly lower (sometimes non-existent) oxygen consumption rate. Our results also showed an increase in the oxygen consumption rate of fresh samples being incubated at 32 degrees C for 24 h. The oxygen consumption rate for all samples reached a plateau within the 15-min measurement period and even the fresh samples did not deplete all the oxygen from the medium. Skin samples ex vivo showed a significantly higher pH than human skin in vivo, and when incubated for 46 h at 32 degrees C, fresh samples had a significantly lower pH than frozen samples. All protocols were reproducible and freshly excised and freshly thawed skin samples showed the highest rates of viability. CONCLUSION: ex vivo skin shows variation of several parameters over time. It is recommended to use two or three techniques for evaluation of skin viability including at least oxygen measurement and an enzyme assay.

Cryopreservation↗

Test for interlayer coherence in a quasi-two-dimensional superconductor.

Peaks in the magnetoresistivity of the layered superconductor kappa - (BEDT-TTF)2Cu(NCS)(2), measured in fields < or =45 T applied within the layers, show that the Fermi surface is extended in the interlayer direction and enable the interlayer transfer integral (t( perpendicular) approximately 0.04 meV) to be deduced. However, the quasiparticle scattering rate tau(-1) is such that Planck's over 2pi/tau approximately 6t( perpendicular), implying that kappa - (BEDT-TTF)2Cu(NCS)(2) meets the criterion used to identify interlayer incoherence. The applicability of this criterion to anisotropic materials is thus shown to be questionable.

Journal Article↗

Chloroxylenol- and triclosan-tolerant bacteria from industrial sources.

Potential development of bacterial tolerance to biocides in the industrial environment is examined in this study. Bacteria tolerant to the phenolic-type agent para-chloro-meta-xylenol (PCMX) and the bis-phenol 2,4,4'-trichloro-2'-hydroxydiphenylether (triclosan) were isolated from industrial sources and identified. Minimum inhibitory concentrations (MICs) were determined and compared with those of culture collection (standard) strains. Of around 100 isolates originally obtained, most were naturally tolerant species such as Pseudomonas spp., or showed low tolerance levels. PCMX-tolerant isolates of Pseudomonas stutzeri and triclosan-tolerant isolates of Citrobacter freundii and Acinetobacter johnsonii were retained for further study. Of these, only P. stutzeri and A. johnsonii showed elevated tolerance compared with the standard strains. There was no evidence of tolerance to the other biocide except for Pseudomonas aeruginosa (an intrinsically tolerant microorganism), and tolerances were stable in the absence of selective pressure except for A. johnsonii. Attempts to select or generate increased tolerance in the standard strains were unsuccessful. High tolerances in terms of MIC were not reflected in terms of lethal effects. This study did not produce any evidence suggesting that the presence of residual biocide concentrations in the industrial environment promotes the emergence of bacterial tolerance for them.

Bacteria↗

Comparative susceptibility of resident and transient hand bacteria to para-chloro-meta-xylenol and triclosan.

AIMS: To determine the susceptibility of planktonic and biofilm-grown strains of resident and transient skin bacteria to the liquid hand soap biocides para-chloro-meta-xylenol (PCMX) and triclosan. METHODS AND RESULTS: Freshly isolated hand bacteria were identified by partial 16S rRNA gene sequencing. Two resident and three transient strains, as well as four exogenous potential transient strains, were selected for biocide susceptibility testing. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of planktonic cells were determined. Resident and transient strains showed a range of susceptibilities to both biocides (PCMX, MIC 12.5-200 mg x l(-1), MBC 100-400 mg x l(-1); triclosan, MIC 0.6- > 40 mg x l(-1), MBC 1.3- > 40 mg x l(-1)). Strains were attached to polystyrene plates for 65 h in 96-well microtitre plates and challenged with biocide to determine the biofilm inhibitory concentration and biofilm eradicating concentration. For all strains tested, biofilms were two- to eightfold less susceptible than planktonic cells to PCMX. CONCLUSIONS: Very few transients were detected on the hand. Transients were not more sensitive than residents to the biocides and susceptibility to PCMX and triclosan was strain dependent. Biofilm-grown strains were less susceptible to PCMX than planktonic cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides increased knowledge about the susceptibility of skin bacteria to biocides present in typical liquid antibacterial hand soaps and suggests that the concentration of biocide employed in such products is in excess of that required to kill the low numbers of transient bacteria typically found on skin.

Anti-Infective Agents, Local↗

The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro.

The effects of chitin [(1 --> 4)-2-acetamido-2-deoxy-beta-D-glucan] and its partially deacetylated derivatives, chitosans, on the proliferation of human dermal fibroblasts and keratinocytes were examined in vitro. Chitosans with relatively high degrees of deacetylation strongly stimulated fibroblast proliferation while samples with lower levels of deacetylation showed less activity. Fraction, CL313A, a shorter chain length, 89% deacetylated chitosan chloride was further evaluated using cultures of fibroblasts derived from a range of human donors. Some fibroblast cultures produced a positive mitogenic response to CL313A treatment with proliferation rates being increased by approximately 50% over the control level at an initial concentration of 50 microg/ml, whilst others showed no stimulation of proliferation or even a slight inhibition (< 10%). The stimulatory effect on fibroblast proliferation required the presence of serum in the culture medium suggesting that the chitosan may be interacting with growth factors present in the serum and potentiating their effect. In contrast to the stimulatory effects on fibroblasts, fraction CL313A inhibited human keratinocyte mitogenesis with up to 40% inhibition of proliferation being observed at 50 microg/ml. In general highly deacetylated chitosans were more active than those with a lower degree of deacetylation. These data demonstrate that highly deacetylated chitosans can modulate human skin cell mitogenesis in vitro. Analysis of their effects on cells in culture may be useful as a screen for their potential activity in vivo as wound healing agents, although in the case of fibroblasts it is important to select appropriate strains of cells for use in the screen.

Biocompatible Materials↗

Determination of the antibacterial efficacy of several antiseptics tested on skin by an 'ex-vivo' test.

There are many skin antiseptics commercially available. Although their antibacterial activity has often been well studied, their potential effectiveness on skin remains poorly documented. To date, in-vivo protocols designed for the testing of the antimicrobial efficacy of antiseptics cannot use, for ethical reasons, pathogenic bacteria or new formulations whose toxicity in human subjects is unknown. An 'ex-vivo' test was recently developed to overcome these problems. Freshly excised human skin from abdominal or breast reduction was placed in a diffusion cell containing a maintenance medium in the recipient compartment. A bacterial inoculum was then applied to the stratum corneum and, after a drying step, antiseptic formulations were evaluated for their antimicrobial activity. Several micro-organisms were investigated: - Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Enterococcus faecalis, vancomycin-resistant Ent. faecium (VRE), S. epidermidis, Pseudomonas aeruginosa and Escherichia coli--with several biocides--para-chloro-meta-xylenol (PCMX, active compound of Dettol), povidone iodine, triclosan (in isopropanol) and chlorhexidine. Results from the ex-vivo test were compared with results obtained in suspension and glass-carrier tests. The bactericidal activity of the biocides depended upon the test performed and results were generally significantly different from one method to the other. All biocides tested in the suspension test achieved >4 log10 reduction in viable bacterial concentrations, apart from povidone iodine tested against Ent. faecalis and VRE. The antibacterial activity of biocides tested in the glass-carrier test was significantly lower than in the suspension test, with the exception of triclosan in isopropanol, which was as effective in both suspension and glass-carrier test. In the ex-vivo test, triclosan in isopropanol achieved a log10 reduction in viable bacterial concentration of 1.105-1.771 (with the exception of P. aeruginosa with 0.758 log10 reduction). PCMX, povidone iodine and chlorhexidine achieved log10 reductions in viable bacterial concentration of 0.303-0.901. Chlorhexidine tested against P. aeruginosa produced a 1.94 log10 reduction in concentration. These results confirm previous observations about the need for testing the antimicrobial activity of antiseptics on skin surface to determine their in-situ efficacy and encourage further the use of the ex-vivo protocol.

Anti-Infective Agents, Local↗

A health-profile comparison of delinquent and homeless youths.

Little is known about the health status and health care needs of homeless and delinquent youths. This study provides medical data (medical history and physical examination) on samples of delinquent (n = 245) and homeless (n = 160) youths in San Francisco, CA. Although homeless youths had somewhat more medical problems than did delinquent youths, both groups had a multiplicity of medical problems, many of which were worse than among the general adolescent population. A substantial percentage of both samples did not have adequate health care coverage. Medical services to high-risk youths should be improved by providing street outreach, public health clinics, and multiservice centers for adolescents.

Adolescent↗

Changes in structure of the bovine milk fat globule membrane on heating whole milk.

The effects of heat-induced interactions between milk fat globule membrane components and skim milk proteins in whole milk on the structure of the membrane were examined by isopycnic sucrose density gradient centrifugation and by using Triton X-100 as a membrane probe. Skim milk components were incorporated into all the lipoprotein fractions separated by density gradient centrifugation. High density complexes, higher in density than those found in the natural milk fat globule membrane, were formed during the heat treatment. Losses of natural membrane polypeptides from the medium and low density lipoproteins were observed on heating. Heating whole milk also altered the rate of release of membrane components by detergent, with decreases in protein released and an increase in phospholipid constituents released. Studies on washed cream indicated that some of the changes in the membrane on heating whole milk occurred due to the heat treatment alone, independent of the interactions with skim milk proteins.

Animals↗

Failure of motion discrimination at high contrasts: evidence for saturation.

The ability of human observers to discriminate the direction of motion of a briefly-presented, slowly moving, 1 c/deg sinusoidal grating varies non-monotonically with the contrast of the grating. At low contrasts, performance improves with increasing contrast, but it reaches a peak between 95% and 100% correct at a contrast of 0.02-0.05. With further increases in contrast performance declines, reaching chance levels at a contrast of about 0.4. Detection of the same stimulus improves with increasing contrast to 100% correct and stays there. This behaviour would be expected if the visual signal which determines direction-of-motion is given by the difference between the responses of paired direction-selective filters tuned to opposite directions of motion and if the responses of these paired filters saturate at modest contrasts.

Contrast Sensitivity↗