A prospective randomised controlled trial of the LMA Supreme vs cuffed tracheal tube as the airway device during percutaneous tracheostomy.

We studied the performance of the LMA Supreme against a cuffed tracheal tube, our standard method of airway control during percutaneous tracheostomy, in 50 consecutive patients from three general critical care units. The primary outcome measure was adequacy of ventilation calculated as the difference in arterial carbon dioxide tension before and after tracheostomy. On an intention-to-treat analysis, there was no difference in the increase in arterial carbon dioxide tension between groups, with a median (IQR [range]) for the LMA Supreme of 0.9 (0.3-1.6 [0-2.8]) kPa, and for the tracheal tube of 0.8 (0.4-1.2 [0-2.5]) kPa, p = 0.82. Eight patients out of 25 (32%) crossed over from the LMA Supreme group to the tracheal tube group before commencement of tracheostomy due to airway or ventilation problems, compared with none out of 25 in the tracheal tube group, p = 0.01, and tracheostomy was postponed in two patients in the LMA Supreme group due to poor oxygenation. There were more clinically important complications in the LMA Supreme group compared with the tracheal tube group.

The effect of a large Legionnaires' disease outbreak in Southwest Edinburgh on acute and critical care services.

OBJECTIVE: The largest outbreak of Legionnaires Disease (LD) in the UK for a decade occurred in Edinburgh in June 2012. We describe the clinical and public health management of the outbreak. SETTING: Three acute hospitals covering an urban area of ~480,000. METHODS: Data were collected on confirmed and suspected cases and minutes of the Incident Management Team meetings were reviewed to identify key actions. RESULTS: Over 1600 urine samples and over 600 sputum samples were tested during the outbreak. 61 patients with pneumonia tested positive for Legionella pneumophila serogroup 1 by urinary antigen detection, culture, respiratory PCR or serology. A further 23 patients with pneumonia were treated as suspected cases on clinical and epidemiological grounds but had no microbiological diagnosis. 36% of confirmed and probable cases required critical care admission. Mean ICU length of stay was 11.3 (±7.6) days and mean hospital length of stay for those who were admitted to ICU was 23.0 (±17.2) days. For all hospitalized patients the mean length of stay was 15.7 (±14) days. In total there were four deaths associated with this outbreak giving an overall case fatality of 6.5%. Hospital and critical care mortality was 6.1% and 9.1%, respectively. CONCLUSION: A significant proportion of patients required prolonged multiple organ support or complex ventilation. Case fatality compared favourably to other recent outbreaks in Europe. Access to rapid diagnostic tests and prompt antibiotic therapy may have mitigated the impact of pre-existing poor health among those affected.

Effect of ciprofloxacin on the activation of the transcription factors nuclear factor kappaB, activator protein-1 and nuclear factor-interleukin-6, and interleukin-6 and interleukin-8 mRNA expression in a human endothelial cell line.

Quinolone antibiotics such as ciprofloxacin modify immune and inflammatory responses in some cells. We have shown previously that ciprofloxacin decreases the accumulation of interleukin (IL)-6 protein from a human endothelial cell line, whilst IL-8 protein production was increased. It is not known whether this occurs through effects on transcription and mRNA expression. We therefore investigated the effect of ciprofloxacin on mRNA for IL-6 and IL-8, and on three transcription factors known to be involved in the regulation of these cytokines. We investigated the effect of ciprofloxacin on tumour necrosis factor alpha- and IL-1beta-mediated activation of the transcription factors nuclear factor kappaB (NFkappaB), activator protein-1 (AP-1) and nuclear factor IL-6 (NF-IL-6) using an electrophoretic mobility shift assay, and the effect on expression of mRNA for IL-6 and IL-8 by reverse transcriptase-PCR in the EAhy926 endothelial cell line. Ciprofloxacin decreased IL-6 mRNA (P<0.05) and increased IL-8 mRNA (P<0.05) expression. Ciprofloxacin did not modulate activation of NFkappaB or AP-1. However, NF-IL-6 binding was decreased in the presence of 100 microg/ml ciprofloxacin (P<0.05). The study shows that ciprofloxacin-mediated decreased IL-6 release by a human endothelial cell line is reflected by decreased mRNA expression and decreased NF-IL-6 but not NFkappaB or AP-1 activation. Increased IL-8 mRNA in response to ciprofloxacin was not reflected by altered transcription factor activation and may represent increased mRNA stability.

Sepsis and the systemic inflammatory response syndrome.

Sepsis and the systemic inflammatory response syndrome are common and represent a major factor in morbidity and mortality in intensive care units and the critically ill. The pathogenesis of these syndromes is becoming increasingly understood and it is hoped that this will result in improved outcome. However, novel treatments have so far failed to live up to the expectations following extensive and promising in vitro and in vivo animal studies. The aim of this review is to detail the currently used definitions of systemic inflammatory response syndrome, sepsis and septic shock and to present an overview of our current understanding of the pathophysiology which underline these conditions.

Increased nuclear factor kappa B activation in critically ill patients who die.

OBJECTIVES: To determine nuclear factor kappa B (NF-kappa B) activation in mononuclear and neutrophils from critically ill patients and to compare NF-kappa B activation with circulating concentrations of interleukin (IL)-6, IL-8, and soluble intercellular adhesion molecule (sICAM)-1. DESIGN: Observational study. SETTING: University Teaching Hospital, eight-bed intensive care unit in northeast Scotland. PATIENTS: Ten patients admitted to the intensive care unit who fulfilled the criteria for systemic inflammatory response syndrome were studied at 0, 24, 48, and 72 hrs. Six healthy volunteers were also studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: NF-kappa B activation was significantly higher in patients compared to healthy volunteers in both neutrophils (p = .001) and mononuclear leukocytes (p = .013). In the six patients who survived to 96 hrs, the level of NF-kappa B activation in mononuclear cells remained constant (p = .9). However, in the four patients who died before 96 hrs, mononuclear cell NF-kappa B activation increased markedly and was significantly higher before death than in those who survived to 96 hrs (p = .0105). NF-kappa B activation in neutrophils similarly remained constant in patients who survived to 96 hrs (p = .4) but did not show the same increase before death. Circulating concentrations of IL-6, IL-8, and sICAM-1 were elevated but were unrelated to leukocyte NF-kappa B activation. CONCLUSIONS: We found NF-kappa B activation in mononuclear and neutrophils in patients with systemic inflammatory response syndrome, which increased markedly before death in mononuclear leukocytes and was not related to plasma IL-6, IL-8, and sICAM-1 concentrations. These data support the need for further study of the role of NF-kappa B activation in mortality from systemic inflammatory response syndrome and sepsis.

Response of erupting human premolars to force application.

To test the hypothesis that human tooth eruption requires a critical time period during which no force is applied to the erupting tooth, the eruption of a maxillary second premolar in the prefunctional stage was recorded during the afternoon or evening hours in eight children, using an optical device based on the principle of Moiré magnification, while intermittent loads of 300-400 mN were applied to the teeth. When a tooth was erupting actively, light force applications either had no discernible effect or decreased the eruption rate for 2 min or less. When a tooth was intruding spontaneously rather than erupting, a varied response was observed, but the rate of intrusion never increased after force application. Often intrusion showed or halted, and especially during the evening, eruption was likely to occur after a force application during an initial period of intrusion. The conclusion is that, although light force applications significantly displace an erupting premolar, they have little or no effect on net eruption, and that a critical time period without force application is not necessary for eruption to occur.

Accuracy of movement tracking with a miniaturized second-generation Moiré device.

The availability of a Nanoform 600, a machine used in the contouring of optical components, with movement capabilities of 12.5 A, made it possible to determine the sensitivity, accuracy and movement tracking ability of a high-resolution measuring device using the principle of Moiré magnification. The Nanoform 600 was programmed to make a series of movements measured by the Moiré device. Comparison of the Moiré measurement with the programmed movements verified that the Moiré device is capable of reliably tracking movements as small as 0.05 microm. Increasing the rate of movement had little effect on linearity. Tracking movements over a 350 microm distance at rates of up to 340 microm per second resulted in a 0.23% error. Intentionally defocusing the Moiré signal did not appreciably affect sensitivity.

A prospective study of lip adaptation during six months of simulated mandibular dental arch expansion.

The stability of dental arch expansion with conventional orthodontic treatments is disappointing. An increase in labial soft tissue pressure resulting from the expansion may contribute to this instability. An 8-month study of lip pressure changes resulting from lip bumper wear has been conducted, but no long-term studies have been conducted on pressure changes resulting from conventional expansion using fixed appliances. The purpose of the current study was to investigate changes in labial soft tissue pressures when conventional expansion was simulated. Twenty-two subjects wore a stent simulating mandibular dental arch expansion. They were instructed to wear the stent full-time. Lip pressure was recorded initially at 1 week, and monthly for 6 months. A repeated measures ANOVA was used for statistical analysis. A statistically significant (P < or = 0.05) increase in pressure was documented after initial insertion of the expansion-simulating stent. The increase was not maintained, suggesting an adaptation of the labial soft tissues.

The rhythms of human premolar eruption: a study using continuous observation.

New optical technology now allows for precise observation of erupting human premolars. Continuous overnight tracking of an erupting tooth with a video microscope system shows that eruption occurs almost exclusively during the early evening. During the day, slight intrusion is likely to occur. When Moiré magnification is used to provide extremely high resolution (0.05 micrometer), slight movements of the erupting tooth in concert with the arterial pulse can be observed, and a previously unknown cyclic movement with a period of 20 to 50 seconds is seen consistently. Rhythms in skeletal growth and tooth eruption suggest that treatment to influence jaw growth and move teeth may be most effective at specific times of the day.

Triggering through CD40 promotes interleukin-4-induced CD23 production and enhanced soluble CD23 release in atopic disease.

The pathogenesis of atopic disease is closely linked to the overproduction of IgE. CD23 and CD40 are two cellular receptors involved in the regulation of IgE production and both receptors are elevated in atopic disease. We have examined the role of CD40 in the regulation of CD23 and soluble CD23 production in healthy and atopic donors. Triggering of the B cell CD40 receptor directly enhances interleukin (IL)-4-mediated up-regulation of CD23 at both the protein and the mRNA level. When atopic donors were studied, the synergistic effect of CD40 triggering on the IL-4-induced up-regulation of CD23 and soluble CD23 (sCD23) was enhanced and there was a relative skewing toward production of sCD23. These studies implicate the CD40 receptor in the hyperproduction of CD23 and sCD23 in atopic disease and suggest that abnormalities may exist in the cellular pathways leading to sCD23 production.

Lip adaptation to simulated dental arch expansion. Part 1: Reliability and precision of two lip pressure measurement mechanisms.

Understanding the influence of lip and tongue pressure on tooth position requires a reliable method of measuring pressure. A transducer with a beam mechanism has been used extensively in the past. A transducer with a diaphragm mechanism has been recently introduced. Comparative in-vivo tests of these transducers have not been published. The purpose of this study was to investigate transducer reliability and precision. Transducers were placed intraorally in 22 subjects, and two lip pressure measurements were recorded. Paired t-tests and interclass correlations were used to evaluate repeatability and reliability. The error of the method was analyzed for each transducer type. Both transducer types produced measurements that were repeatable and reliable. The error was smaller for the diaphragm transducer. The diaphragm transducer is more precise.

Lip adaptation to simulated dental arch expansion. Part 2: One week of simulated expansion.

An increase in resting lip pressure and the resulting disruption of the intraoral pressure equilibrium may be responsible for the poor stability found with orthodontically expanded dentitions. Passive expansion strategies seek improved stability by altering lip pressure, thus creating a new equilibrium. One of these strategies has been shown to alter pressure favorably. However, pressure changes associated with conventional expansion need to be studied before conclusions regarding the superiority of passive expansion can be drawn. The purpose of this study was to examine lip pressure changes after 1 week of simulated conventional expansion. Twenty-two subjects agreed to wear a mandibular expansion-simulating stent full-time for 1 week. Resting pressure was measured in the midline and right canine areas. Midline lip pressure decreased significantly after 1 week. Resting pressure was measured in the midline and right canine areas. Midline lip pressure decreased significantly after 1 week while pressure in the canine area did not change significantly. This finding suggests an adaptive response that varies according to anatomic location.

The application of Moire magnification to high-resolution studies of human premolar eruption.

The optical phenomenon of Moire magnification can be used to provide real-time measurements of the position of an erupting human premolar, with a resolution of 0.1 micron or better. A new instrument for this purpose, which allows repeated measurements in the same individual, is described. Cyclic changes in the position of the erupting tooth in concert with the heartbeat, with a magnitude of 0.05-0.35 micron, can be discerned. An unusual cyclic rhythm, with a period of 20-50 s, was observed.

Activation of human thymocytes after infection by EBV.

The discovery of EBV in certain T cell malignancies and the expression of the EBV receptor, CR2/CD21, on a population of immature thymocytes, T lymphoblastoid cell lines, and childhood acute T lymphoblastic leukemia cells suggested that EBV-receptor interactions on T cells may be of importance. We have shown that, within the thymus, a population of large, immature cells expresses CD21. EBV altered the activation responses of immature thymocytes in vitro. Triggering through CD2 is mitogenic for mature, but not immature, T cells. However, during infection by EBV, ligation of CD2 caused thymocytes to proliferate in the absence of exogenous cytokines. This function was a result of the interaction of EBV with its receptor, CD21, but was caused by infection rather than surface signaling, because neither specific mAb nor the P3HR-1 strain of virus mimicked the effect of B95-8. Immature thymocytes were infected by EBV, as determined by the internalization of the viral genome and its transcriptional activity. Consistent with the activity of B95-8, EBNA-2 transcripts were identified within infected thymocyte populations. In addition, components of the viral replicative pathway were expressed during infection of thymocytes. These components included transcription of BZLF-1, an early gene that characterizes EBV-infected B cells after disruption of latency. A second transcript was identified as encoding the recently characterized RAZ, which also is associated with replicative infection. The consequences of EBV infection of T cells at an early stage of differentiation may lead to failure of normal T cell repertoire development, autoimmunity, or malignancy.

Model of Epstein-Barr virus infection of human thymocytes: expression of viral genome and impact on cellular receptor expression in the T-lymphoblastic cell line, HPB-ALL.

Infection of B lymphocytes and epithelial tissue by Epstein-Barr virus (EBV) is associated with malignancy and autoimmunity. The cellular receptor for EBV has been identified as CD21 (CR2). A molecule, which is biochemically and immunologically similar to B-cell CD21, has been identified on a subpopulation of immature thymocytes, suggesting a role for this molecule in the regulation of T-cell development and further suggesting that immature T cells might be susceptible to EBV infection. A growing body of literature now documents the presence of EBV in tumors of T-cell origin. We have evaluated the susceptibility of the human immature T cell line, HPB-ALL, to infection by EBV. Electron microscopy studies showed a rapid internalization of virus by HPB cells. Southern blotting showed the intracellular presence of linear EBV genomes, and components of the virus replicative cycle were identified. Expression of the BamHI Z region of the genome, encoding the nuclear protein, ZEBRA, which is strictly associated with productive infection in B cells, was detected in HPB-ALL cells. A spliced variant of Z, RAZ, was also identified. Cell surface expression of EBV late antigens was observed to occur transiently. Infection of HPB cells was also accompanied by altered expression of T-cell surface molecules involved in antigen recognition, a process critical to normal development of the T-cell repertoire. Delineation of the outcome of T-cell infection by EBV may lead to a better understanding of the role of this virus in autoimmune processes and malignancy.

Regulation of CD23 expression by IL-4 and corticosteroid in human B lymphocytes. Altered response after EBV infection.

Cellular CD23 has been implicated in various biologic and pathologic processes. Here, we have studied the regulation of B cell CD23 expression and function by the synthetic corticosteroid, dexamethasone (DEX). We report that DEX acts directly on B lymphocytes to down-regulate IL-4-induced CD23 expression, whereas in parallel the IL-4R is up-regulated. Down-regulation of CD23 occurred at the cell surface and for shed material in culture medium. EBV infection of B cells is linked to development of lymphoproliferative diseases, including lymphoma, and there is evidence that EBV-stimulated CD23 expression may be instrumental in the inappropriate survival of infected cells. We have determined that treatment of EBV-infected cells with IL-4 leads to a synergistic up-regulation of B cell CD23. Furthermore, infection of B cells by EBV introduced a relative resistance to the down-regulatory effects of DEX on IL-4-induced CD23 expression.

Magnetostrictive calibration of a precision optical measurement device for studies of tooth eruption.

In order to calibrate a precision-measuring instrument for studies of tooth eruption, a calibration device capable of repositioning an optical grating in steps accurate to at least 0.02 microns was required. At this level, piezoelectric and similar pushers encounter problems. A new calibration device based on the magnetostrictive properties of nickel was developed. Accuracy better than 0.02 microns was verified by relating its movements to the wavelength of the green line of mercury, and the device was successfully used to calibrate the instrument for establishing tooth position. Magnetostriction offers a way to calibrate precision measurement instruments for other applications.

Monitoring microvascular reactivity in dental subjects.

In this section of a larger study, a system for monitoring changes in the microcirculation, in humans in the dental setting, is described. The technique involves clinical nailfold capillary photomicroscopy and electronic image-scan measurements. The system was tested using reactive hyperemia after vascular occlusion; it proved reliable and sufficiently sensitive for measuring vascular reactivity in humans. (In a subsequent paper, clinical findings relative to the use of this technique with patients undergoing nitrous oxide/oxygen anesthesia will be presented).The importance of the microcirculation for the integrity of the tissues cannot be overemphasized. Since the term "microcirculation" can be defined as the microscopic subdivisions of the vascular system that lie within the tissue proper and are exposed to its immediate environment,(1) it is evident that most of the exchange of nutrients and waste products occuring in the tissue will occur at this level. Furthermore, the adequacy of tissue perfusion during drug administration, or during and after anesthesia, is dependent on the adequacy and reactivity of this subdivision of the vascular system.(2)A basic prerequisite to the understanding of microcirculatory function in a given vascular bed is the precise quantitation of dimensional changes in those vessels(3). Dynamic measurements in vivo are required, since it is difficult, if not impossible, to ensure that the dimensions obtained from fixed tissue specimens are accurate measures of those occurring in the living state. This is especially true where vessel dimensions are rapidly changing in response to endogenous or exogenous influences. Unfortunately the task of in vivo measurement of microvascular dimensions is difficult in most microcirculatory beds. Since the vessels are an integral part of a threedimensional structure,(4) the tasks of visualizing, isolating and measuring the vessels are formidable. These difficulties are compounded if the particular vessels to be studied are in human subjects where surgical intervention is unacceptable. For these reasons, previous studies of dimensional changes in the microcirculation, involving a variety of techniques (still photography, cinematography, television microscopy,(5) image-scanning,(6) image-shearing(7,8) and optical density measurements(9)), were almost always carried out in animals.In order to determine the effects of drugs and anesthetic gases on the peripheral microcirculation in human subjects undergoing dental treatment, we have employed a non-invasive photomicrographic method to measure planar dimensional changes in human nailfold capillaries. In this report we will describe this technique, its use in measuring microcirculatory changes in humans in a dental setting, and the results of a study undertaken to determine if it is sensitive enough to measure an induced change in vascular dimensions.