Hydrogen crystallization in low-density aerogels.

Crystallization of liquids confined in disordered low-density nanoporous scaffolds is poorly understood. Here, we use relaxation calorimetry to study the liquid-solid phase transition of H2 in a series of silica and carbon (nanotube- and graphene-based) aerogels with porosities ≳94%. Results show that freezing temperatures of H2 inside all the aerogels studied are depressed but do not follow predictions of the Gibbs-Thomson theory based on average pore diameters measured by conventional gas sorption techniques. Instead, we find that, for each material family investigated, the depression of average freezing temperatures scales linearly with the ratio of the internal surface area (measured by gas sorption) and the total pore volume derived from the density of aerogel monoliths. The slope of such linear dependences is, however, different for silica and carbon aerogels, which we attribute to microporosity of carbons and the presence of macropores in silica aerogels. Our results have important implications for the analysis of pore size distributions of low-density nanoporous materials and for controlling crystallization of fuel layers in targets for thermonuclear fusion energy applications.

Freezing and melting of hydrogen confined in nanoporous silica.

Thermodynamic properties of condensed hydrogen in geometric confinement remain poorly understood. Here, we use relaxation calorimetry to study solidification and melting of H2 in a series of Vycor-type nanoporous silica glasses with interconnected pores with average diameters in a wide range of ∼100-3000 Å. We find that the depression of freezing and melting temperatures for this quantum system follows the classical Gibbs-Thomson-like behavior, scaling inversely with the pore size when correlated to pore diameters measured directly by electron microscopy, rather than conventional gas sorption techniques. The shapes of pore size distributions derived from hydrogen thermoporometry are, however, more complex than those measured by gas sorption. The ratio between temperatures of the depression of freezing and melting suggests that the actual pore geometry in Vycor-type nanoporous glasses deviates from cylindrical.

Chronic tooth pulp inflammation induces persistent expression of phosphorylated ERK (pERK) and phosphorylated p38 (pp38) in trigeminal subnucleus caudalis.

BACKGROUND: Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase are transiently phosphorylated (activated) in the spinal cord and trigeminal nucleus by acute noxious stimuli. Acute stimulation of dental pulp induces short-lived ERK activation in trigeminal subnucleus caudalis (Vc), and p38 inhibition attenuates short-term sensitization in Vc induced by acute pulpal stimulation. We have developed a model to study central changes following chronic inflammation of dental pulp that induces long-term sensitization. Here, we examine the effects of chronic inflammation and acute stimulation on the expression of phosphorylated ERK (pERK), phosphorylated p38 (pp38) and Fos in Vc. RESULTS: Chronic inflammation alone induced bilateral expression of pERK and pp38 in Vc, but did not induce Fos expression. Stimulation of both non-inflamed and inflamed pulps significantly increased pERK and pp38 bilaterally; expression was greatest in inflamed, stimulated animals, and was similar following 10-min and 60-min stimulation. Stimulation for 60 min, but not 10 min, induced Fos in ipsilateral Vc; Fos expression was significantly greater in inflamed, stimulated animals. pERK was present in both neurons and astrocytes; pp38 was present in neurons and other non-neuronal, non-astrocytic cell types. CONCLUSIONS: This study provides the first demonstration that chronic inflammation of tooth pulp induces persistent bilateral activation of ERK and p38 within Vc, and that this activation is further increased by acute stimulation. This altered activity in intracellular signaling is likely to be linked to the sensitization that is seen in our animal model and in patients with pulpitis. Our data indicate that pERK and pp38 are more accurate markers of central change than Fos expression. In our model, localization of pERK and pp38 within specific cell types differs from that seen following acute stimulation. This may indicate specific roles for different cell types in the induction and maintenance of pulpitic and other types of pain.

Relaxation calorimeter for hydrogen thermoporometry.

A relaxation calorimeter for measuring the heat capacity of hydrogen isotopes in nanoporous solids is described. Apparatus' features include (i) cooling by a pulse tube refrigerator, (ii) a modular design, allowing for rapid reconfiguration and sample turn around, (iii) a thermal stability of ≲1 mK, and (iv) a bottom temperature of ~5 K. The calorimeter is tested on effective heat capacity measurements of H2 in Vycor (silica) nanoporous glass, yielding a very detailed pore size distribution analysis with an effectively sub-Angstrom resolution.

Evidence for anti-inflammatory and putative analgesic effects of a monoclonal antibody to calcitonin gene-related peptide.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is a powerful pro-inflammatory mediator thought to play a significant role in the development of inflammation and pain. We investigated the role of CGRP in trigeminal inflammatory pain by determining the ability of a monoclonal antibody to CGRP to modify central Fos expression in response to stimulation of the inflamed ferret tooth pulp. We also assessed the effect of the antibody on pulpal inflammation. METHODS: Ten adult ferrets were prepared under anaesthesia to allow stimulation of the upper and lower left canine pulps, recording from the digastric muscle and intravenous injections at subsequent experiments. In all animals, pulpal inflammation was induced by introducing human caries into a deep buccal cavity. Four days later animals were treated intravenously with either CGRP antibody (n=5) or vehicle (n=5). After a further 2 days animals were re-anaesthetised and the tooth pulps stimulated at 10 times jaw-opening reflex threshold. Brainstems and tooth pulps were processed immunohistochemically for Fos and the common leucocyte marker CD45, respectively. RESULTS: Fos was expressed in ipsilateral trigeminal subnuclei caudalis (Vc) and oralis (Vo). Significantly fewer Fos-positive nuclei were present within Vc of CGRP antibody-treated animals (p=0.003 vs vehicle-treated). Mean percentage area of staining for CD45 was significantly less in antibody-treated animals (p=0.04 vs vehicle-treated). CONCLUSIONS: This is the first direct evidence that sequestration of CGRP has anti-inflammatory and putative analgesic effects. Previous studies using this Fos model have demonstrated that it is able to predict clinical analgesic efficacy. Thus these data indicate that this antibody may have analgesic effects in dental pain and other types of inflammatory-mediated transmission, and suggest that this is in part due to peripheral anti-inflammatory effects.

A role for protein kinase intracellular messengers in substance P- and nociceptor afferent-mediated excitation and expression of the transcription factor Fos in rat dorsal horn neurons in vitro.

Expression of the inducible transcription factor Fos in the spinal dorsal horn in vivo is associated with nociceptive afferent activation, but the underlying stimulation-transcription pathway is less clear. This in vitro spinal cord study concerns the role of protein kinase A and C second messengers in substance P receptor (NK1R)-mediated or nociceptive afferent-evoked neuronal excitation and Fos expression. Nociceptive afferent (dorsal root) stimulation of isolated spinal cords (10-14 day old rats) evoked a 'prolonged' excitatory polysynaptic potential (DR-EPSP) that was attenuated (P < 0.05) by: the protein kinase A inhibitor, Rp-cAMP; the protein kinase C inhibitor, bisindolymaleimide I; and the selective NK1R antagonist, GR82334. Neuronal excitations induced by the NK1R agonist [Sar9,Met(O2)11]-SP were attenuated by Rp-cAMP, bisindolymaleimide I and GR82334. Effects of the protein kinase A and C inhibitors on the DR-EPSP or the [Sar9,Met(O2)11]-SP-induced depolarization were nonadditive, suggesting convergence of these intracellular signalling pathways onto a common final target. Nociceptor afferent-induced Fos, detected by immunohistochemistry in superficial and deep dorsal horn laminae, was attenuated by Rp-cAMP, bisindolymaleimide I and GR82334. In spinal cords pretreated with TTX to eliminate indirect neuronal activation, [Sar9,Met(O2)11]-SP (1-20 microM) elicited a dose-related expression of Fos that was reduced by Rp-cAMP, bisindolymaleimide I and GR82334. The effects of these inhibitors were most pronounced in the deep laminae. These data support a causal relationship between protein kinase A- or C-dependent signal transduction, nociceptive afferent- or NK1R-induced neuronal excitation and Fos expression in dorsal horn. Implications for short- versus long-term modulation of nociceptive circuitry are discussed.

Peripheral inflammation reduces the response of spinal dorsal horn neurons to an NK3 receptor agonist.

The neurokinin receptors NK1 and NK3 are involved in processing nociceptive information in the spinal dorsal horn and in central changes following persistent peripheral injury. However, little is known about functional changes in these receptor systems, particularly the NK3 receptor. We have performed intracellular recordings from spinal dorsal horn neurons in vitro, using spinal cords obtained both from control rats and from those with a peripheral inflammation induced by carrageenan. Application of the NK1 receptor agonist, [Sar(9), Met(O2)(11)]Substance P and the NK3 receptor agonist, Senktide, produced slow, long lasting depolarizations. The Senktide- but not [Sar(9), Met(O2)(11)]Substance P-induced depolarizations were significantly smaller in carrageenan-treated rats. These data indicate an altered role for the NK3 receptor in the spinal dorsal horn following acute peripheral inflammation.

Intraoperative bacterial contamination in operations for joint replacement.

All surgical operations have the potential for contamination, and the equipment used can harbour bacteria. We collected samples from 100 elective primary hip and knee arthroplasties. These showed rates of contamination of 11.4% for the sucker tips, 14.5% for light handles, 9.4% for skin blades and 3.2% for the inside blades used during surgery; 28.7% of gloves used for preparation were also contaminated. Of the samples taken from the collection bags used during hip arthroplasty, 20% grew bacteria, which represents a significant microbial reservoir. Also, 17% of theatre gowns were contaminated at the end of the operation. Contamination was found in 10% of the needles used during closure of the fascia. Overall, 76% of the organisms grown were coagulase-negative staphylococcus. A total of 63% of operations showed contamination in the field of operation. Some changes in practice are suggested. Follow-up for a minimum of two years revealed one deep infection but the organism was not identified as a contaminant. These data provide a baseline for studying the bacteriology of the surgery of revision arthroplasty.

Infection control and prevention of Clostridium difficile infection.

Clostridium difficile has become a major problem as a nosocomial pathogen that is associated with the use of antibiotics. In the prevention and control of C. difficile disease it is important that programmes are directed at primary and secondary prevention. The three main elements of prevention are: (i) restricted use of antibiotics; (ii) strict enteric precautions when looking after patients with diarrhoea; and (iii) meticulous cleaning of clinical areas. Although poor handwashing is known to play a key role in the spread of infection, there is evidence that compliance with handwashing protocols is low in many hospitals. Infection control teams need to continue to develop creative education programmes to improve compliance with simple infection control procedures. Consideration needs to be given to ensure that patients have access to handwashing and are well informed about infection prevention. Further work needs to be carried out to establish the efficacy of disinfectants in the environment and the identification of a user-friendly, effective sporicide. The importance of both thorough cleaning with detergents to reduce the number of spores in the environment, and clean equipment for each patient should continue to be emphasized.

Identification of outbreak-associated and other strains of Clostridium difficile by numerical analysis of SDS-PAGE protein patterns.

Seventy-three cultures of Clostridium difficile isolated both during, and in the period immediately following, an outbreak of infection in a group of three hospitals, were characterized by one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole-cell proteins. Each protein pattern was characterized by the presence of one or two dense bands which were highly reproducible. The protein patterns were used as the basis for a numerical analysis which divided the strains into five phenons (electrophoretic or EP types). The majority, 60 of the 73 cultures, belonged to a single phenon which included strains from both patients and the environment. We conclude that high-resolution SDS-PAGE of proteins provides an effective method for typing C. difficile and therefore for tracing the possible spread of epidemic strains in hospitals and other institutions, thereby allowing a better understanding of the epidemiology of the organism.

Management and control of a large outbreak of diarrhoea due to Clostridium difficile.

In the six-month period 1 November 1991 to 1 May 1992 175 patients developed diarrhoea due to Clostridium difficile in three hospitals in Manchester, UK. Most patients (90%) were over 60 years old and had been admitted to acute geriatric or medical wards with other illnesses. Infection is thought to have contributed to 17 deaths. Twenty-two patients relapsed clinically after antibiotic treatment. The outbreak began in one ward and affected 15 patients and two nurses. During the following months cases occurred on 34 wards. The pattern of spread suggested that a ward index case was followed by several secondary cases. Pyrolysis mass spectrometry showed that 79% of isolates of C. difficile belong to a single cluster and this putative outbreak strain also extensively colonizes the hospital environment. It was also responsible for a smaller outbreak in 1991 and many 'sporadic' cases in our hospitals before then. An outbreak control team was convened at an early stage and expert opinion co-opted. Infection control measures included: intensive education of staff; increased vigilance; strict enteric precautions; cohort nursing in a designated ward; rigorous cleaning procedures including emptying and 'deep' cleaning of wards where several cases had occurred; restriction of staff and patient movement; and restriction of antibiotic use. Subsequent to these measures there has been a substantial and sustained decrease in the number of new cases.

Nursing priorities and the contribution of the International Federation of Infection Control.

Much thought has been given to the role of the nurse in the future. Concern has been expressed that nurses are becoming preoccupied with technology which, despite the undoubted advantages, is diverting attention from simple prevention and control of infection measures. In countries with minimal resources the appointment of a full-time infection control nurse may not be feasible. Therefore, attempts should be made to train all nurses in the basic principles and practice of the prevention and control of nosocomial infection. This training should be designed to suit the needs of the individual country taking into account the culture, common infections and the patient population. The International Federation of Infection Control should be able to assist with this type of education. The nursing priorities for each country will vary and, whereas handwashing will remain a major priority, routine surveillance may be impracticable. The International Federation of Infection Control which was founded in 1987 is planning to take a lead in helping to set up organizations for infection control workers and to improve communications between organizations in different countries.