Medical-grade polycaprolactone scaffolds made by melt electrospinning writing for oral bone regeneration - a pilot study in vitro.

BACKGROUND: The spectrum of indications for the use of membranes and scaffolds in the field of oral and maxillofacial surgery includes, amongst others, guided bone regeneration (GBR). Currently available membrane systems face certain disadvantages such as difficult clinical handling, inconsistent degradation, undirected cell growth and a lack of stability that often complicate their application. Therefore, new membranes which can overcome these issues are of great interest in this field. METHODS: In this pilot study, we investigated polycaprolactone (PCL) scaffolds intended to enhance oral wound healing by means of melt electrospinning writing (MEW), which allowed for three-dimensional (3D) printing of micron scale fibers and very exact fiber placement. A singular set of box-shaped scaffolds of different sizes consisting of medical-grade PCL was examined and the scaffolds' morphology was evaluated via scanning electron microscopy (SEM). Each prototype sample with box sizes of 225 µm, 300 µm, 375 µm, 450 µm and 500 µm was assessed for cytotoxicity and cell growth by seeding each scaffold with human osteoblast-like cell line MG63. RESULTS: All scaffolds demonstrated good cytocompatibility according to cell viability, protein concentration, and cell number. SEM analysis revealed an exact fiber placement of the MEW scaffolds and the growth of viable MG63 cells on them. For the examined box-shaped scaffolds with pore sizes between 225 µm and 500 µm, a preferred box size for initial osteoblast attachment could not be found. CONCLUSIONS: These well-defined 3D scaffolds consisting of medical-grade materials optimized for cell attachment and cell growth hold the key to a promising new approach in GBR in oral and maxillofacial surgery.

Integrating asthma hazard characterization methods for consumer products.

Despite extensive study, definitive conclusions regarding the relationship between asthma and consumer products remain elusive. Uncertainties reflect the multi-faceted nature of asthma (i.e., contributions of immunologic and non-immunologic mechanisms). Many substances used in consumer products are associated with occupational asthma or asthma-like syndromes. However, risk assessment methods do not adequately predict the potential for consumer product exposures to trigger asthma and related syndromes under lower-level end-user conditions. A decision tree system is required to characterize asthma and respiratory-related hazards associated with consumer products. A system can be built to incorporate the best features of existing guidance, frameworks, and models using a weight-of-evidence (WoE) approach. With this goal in mind, we have evaluated chemical hazard characterization methods for asthma and asthma-like responses. Despite the wealth of information available, current hazard characterization methods do not definitively identify whether a particular ingredient will cause or exacerbate asthma, asthma-like responses, or sensitization of the respiratory tract at lower levels associated with consumer product use. Effective use of hierarchical lines of evidence relies on consideration of the relevance and potency of assays, organization of assays by mode of action, and better assay validation. It is anticipated that the analysis of existing methods will support the development of a refined WoE approach.

Driving with navigational instructions: Investigating user behaviour and performance.

This paper reports the results of an inter-disciplinary study investigating user preferences and performance in relation to spoken in-car route guidance. In-car navigation systems are becoming increasingly popular. However, despite large amounts of research assessing the presentation of spatial information, and the usability and interaction issues surrounding the interfaces, there has been much less investigation of the impacts of auditory presentation of route information. We addressed this issue using a multi-disciplinary approach to collect both qualitative and quantitative data through questionnaires and user experiments. Our research identified a user preference for auditory presentation of route information, as well as a memory advantage for auditory over visual presentation. We also found that simple auditory route instructions could be followed without significant interference to a simulated driving task, whereas more complex auditory instructions did cause interference. Taken together, this research highlights the importance of the design of spoken route guidance instructions in minimising the cognitive demands that they impose.

Metal ion levels following resurfacing arthroplasty of the hip: serial results over a ten-year period.

We report serum metal ion level data in patients with unilateral and bilateral hip resurfacing over a ten-year period. In these patients there is an increase in both cobalt and chromium levels above the accepted reference ranges during the first 18 months after operation. Metal ion levels remain elevated, but decline slowly for up to five years. However, the levels then appear to start rising again in some patients up to the ten-year mark. There was no significant difference in cobalt or chromium levels between men and women. These findings appear to differ from much of the current literature. The clinical significance of a raised metal ion level remains under investigation.

Expression of CC chemokine receptor 7 in tonsillar cancer predicts cervical nodal metastasis, systemic relapse and survival.

The aim of this study was to evaluate the expression of CC chemokine receptor 7 (CCR7) in squamous cell cancer of the tonsil with respect to patterns of spread, relapse-free, overall and disease-specific survival. Eighty-four patients with squamous cell cancer of the tonsil were identified. There was a male predominance of 3 : 1 and the median age at diagnosis was 53 (range 35-86) years. The median duration of follow-up was 33 (range 2-124) months. There was a significant association between CCR7 immunopositivity and synchronous cervical nodal metastasis in patients with tonsillar cancer (Spearman's correlation coefficient 0.564; P<0.001). Relapse-free (P=0.0175), overall (P=0.0136) and disease-specific (P=0.0062) survival rates were significantly lower in patients whose tumours expressed high levels of CCR7. On multivariate analysis, high-level CCR7 staining predicted relapse-free (hazard ratio 3.0, 95% confidence intervals 1.1-8.0, P=0.026) and disease-specific (hazard ratio 10.2, 95% confidence intervals 2.1-48.6, P=0.004) survival. Fifteen percent of patients with the highest level of tumour CCR7 immunopositivity relapsed with systemic metastases. These data demonstrated that CCR7 expression was associated with cervical nodal and systemic metastases from tonsillar cancers. High levels of CCR7 expression predicted a poor prognosis.

Preventing annoyance from odors in spaceflight: a method for evaluating the sensory impact of rodent housing.

For the scientific community, the ability to fly mice under weightless conditions in space offers several advantages over the use of rats. These advantages include the option of testing a range of transgenic animals, the ability to increase the number of animals that can be flown, and reduced demands on shuttle resources (food, water, animal mass) and crew time (for water refill). Mice have been flown in animal enclosure module (AEM) hardware only once [Space Shuttle Transport System (STS)-90] and were dissected early in the mission, whereas rats have been flown in the AEM on >20 missions. This has been due, in part, to concerns that strong and annoying odors from mouse urine (vs. rat urine) will interfere with crew performance in the shuttle middeck. To screen and approve mice for flight, a method was developed to evaluate the odor containment performance of AEMs housing female C57BL/6J mice compared with AEMs housing Sprague-Dawley rats across a 21-day test period. Based on the results of this test, consensus was reached that mice could fly in the AEM hardware for up to 17 days (including prelaunch and contingency) and that the AEM hardware would likely contain odors beyond this duration. Human sensory and electronic nose analysis of the AEMs postflight demonstrated their success in containing odors from mice for the mission duration of STS-108 (13 days). Although this paper focuses specifically on odor evaluations for the space shuttle, the concern is applicable to any confined, closed-system environment for human habitation.

Assessment of ocular and nasal irritation in asthmatics resulting from fragrance exposure.

BACKGROUND: Many asthmatics report worsening of symptoms following exposure to odours and sensory irritants commonly found in household and cosmetic products. Despite this, little evidence exists to confirm the degree to which such subjective reports are correlated with localized, objective changes in the upper or lower airways following a fragranced product exposure. OBJECTIVE: Subjective symptom reports were compared to objective measures in mild asthmatics, moderate asthmatics and non-asthmatics following exposure to one of two fragranced household aerosol mixtures and a clean air control condition to determine if asthmatics reported greater subjective symptoms of nasal congestion or exhibited objective measures of elevated ocular irritation and nasal congestion following exposure than did healthy controls. METHODS: Measures of nasal mucosal swelling, using acoustic rhinometry, and photographic assessments of ocular hyperemia, using macro-photography, were taken before exposure, immediately after an initial 5-min exposure and again following a 30-min exposure to either of two, fragranced aerosol products and a clean air control. Self-reports of nasal patency at each time-point were also obtained. RESULTS: Although moderate asthmatics tended to report more nasal congestion following fragranced product exposure than did non-asthmatics, no exposure-related changes in ocular redness or nasal mucosal swelling were observed among the three groups. Spirometry readings also failed to show evidence of any exposure-related changes in pulmonary function. CONCLUSION: Despite claims that exposure to fragranced products may trigger ocular and respiratory symptoms among asthmatics, we found no evidence that 30 min of exposure to one of two fragranced aerosols elicited objective adverse effects in the ocular or nasal mucosa of mild and moderate asthmatics. While physiological mechanisms of fragrance impact may yet be responsible for some of the adverse reports among asthmatics following fragrance exposure, such reports may also reflect a non-physiological locus of symptom perception triggered by other sensory cues.

Distribution and significance of epithelial types in columnar-lined esophagus.

An abnormal columnar-lined esophagus (CLE) is characterized by the presence of cardiac mucosa (CM) oxynto-cardiac mucosa (OCM), and intestinal metaplastic epithelium (IM) between gastric oxyntic mucosa and esophageal squamous epithelium. Thirty-two patients with CLE measuring 2-16 cm long had 5-37 biopsies per patient that showed CM, OCM, or IM for a total of 424 biopsies. Detailed mapping of the distribution of epithelial types within the CLE showed a distinct zonation of epithelial types; CM was present throughout the CLE, whereas OCM and IM tended to occur in the distal and proximal part of the CLE, respectively. All 32 patients (64 of 68 biopsies) showed IM at the most proximal level, compared with 22 of 32 patients (40 of 102 biopsies) in the most distal level biopsies. The density of goblet cells was highest in the most proximal level. The differences in prevalence and density of goblet cells between most proximal and most distal level biopsies were highly significant. These data suggest that for a given number of biopsies within the CLE, the likelihood of finding IM is greatest when the biopsies are concentrated in the most proximal area of the CLE. We suggest that glandular transformation of squamous epithelium results in CM. which evolves into OCM and IM by development of specialized parietal cells and goblet cells, respectively. The severity and nature of reflux cause these epithelial transformations in a constant and predictable manner. Recognition of these changes permits the development of morphologic definitions of reflux disease and the characterization of the sequence of epithelial changes that represent the reflux-adenocarcinoma sequence.

Evaluating the human response to sensory irritation: implications for setting occupational exposure limits.

Although animal models of sensory irritation have led to the development of useful assays for evaluating the potency of chemical irritants, the importance of conducting human exposure studies to model and understand the human response to sensory irritants cannot be minimized. In recent years a series of tests have been developed for humans that can be safely conducted and that can provide excellent data on which to base occupational exposure limits. This article delineates the major issues involved in the evaluations of sensory irritation in humans. Among these issues are the differences between odor and irritation, irritation and slight toxicity, adaptation and habituation, as well as personal expectation about discomfort and the reported irritation. The article also describes psychophysiological and electrophysiological methods for assessing sensory irritation. Some of the possible confounders that can influence the results of human tests involving sensory irritants are addressed.

Psychophysical methods in the study of olfaction and respiratory tract irritation.

This article describes the fundamentals of olfaction and irritation perception and the dominant psychophysical methods for the assessment of olfaction and respiratory tract irritation. It also discusses factors that determine the olfactory and irritant response (ranging from the physicochemical properties of the stimulus to the physiological and cognitive characteristics of the individual). Because the vast majority of volatile chemicals stimulate the olfactory system at concentrations well below that at which they will elicit trigeminal activation, the evaluation of irritation from volatiles is often confounded by the perception of odor. Several methods have been used for studying the perception of irritation, without the influence of olfaction. The perception and reports of acute adverse effects of odor, annoyance, and irritation from volatile chemicals have multiple determinants. Understanding the perceptual impact of chemicals under environmentally realistic conditions requires attending to both the sensory and the psychological impact of those exposures. The review, which is largely based on presentations given by Dr. Richard Doty and Dr. William Cain, concludes by discussing the importance of the psychophysical approach, which considers physiochemical, subject, experimental, and cognitive/ psychological factors, for research in the chemical senses.

Dupuytren's disease of the wrist.

The authors present the case of a 47-year-old female who presents with bilateral Dupuytren's disease of the wrist. To date, three English language papers reporting on the occurrence of Dupuytren's disease at the wrist have been presented. These reports represent cases in males with unilateral involvement of their wrists where there has been primary Dupuytren's disease of the palm apparently spreading to the wrist in continuity. Our case demonstrates isolated bilateral Dupuytren's disease of the wrist in a female. The authors feel that this clinical presentation is rare and that consideration should be given to the diagnosis of Dupuytren's disease when there is a painful lesion of the soft tissues adjacent to the wrist. The presence of bilateral lesions at the wrist should further heighten the suspicion of Dupuytren's disease even in the absence of associated disease in the palm or fingers. A discussion of the previous reports is included.

Psychophysical and behavioral characteristics of olfactory adaptation.

Sensory adaptation allows organisms to reach behavioral equilibrium with the ambient environment and respond primarily to changes in stimulation. Given its functional significance, it is not surprising that adaptation in the olfactory system exhibits many of the same characteristics as adaptation in other sensory systems, including vision. Repeated or prolonged exposure to an odorant typically leads to stimulus-specific decreases in olfactory sensitivity to that odorant, but sensitivity recovers over time in the absence of further exposure. Psychophysical analysis shows that olfactory adaptation results in elevations in odor thresholds and in reduced responsiveness to suprathreshold stimulation. Further, the magnitude of the decrease and the time course of adaptation and recovery are dependent on the concentration of the odor and on the duration of exposure. It is generally agreed that olfactory adaptation can occur at multiple levels in the olfactory system and can involve both peripheral (receptor level) and more central (post-receptor) components. Evidence for peripheral and central involvement comes from studies showing that monorhinal stimulation results in adaptation in both the ipsilateral and contralateral nostril, although the degree of adaptation in the ipsilateral nostril is more profound and recovery is slower. Additional evidence for central involvement comes from studies that have found relatively small decreases in peripheral response following repeated stimulation despite substantial reductions in perceived intensity. Most psychophysical studies of adaptation, however, have not differentiated the peripheral and central processes. Although relatively few in number, studies of the parametric features of olfactory adaptation in both vertebrate (e.g. rat) and invertebrate (e.g. Drosophila, Caenorhabditis elegans) animal models appear to replicate the findings in psychophysical studies of adult humans. Despite the broad overall similarity of olfactory adaptation to adaptation in other sensory systems, olfactory adaptation exhibits some unique features. Adaptation in olfaction has been shown to be very long-lasting in some cases and may be modulated by the contribution of pre-neural events and physico-chemical properties of the odorant molecules that govern diffusion to receptor sites and post-receptor clearance.

Chemosensory function and response in idiopathic environmental intolerance.

This chapter reviews the current literature on the possible role of olfactory and trigeminal chemosensory function in idiopathic environmental intolerances (IEI). Two general points emerge from the review. First, studies of chemosensory function in IEI patients indicate that, despite their self-reported "heightened sensitivity" and enhanced responsivity to environmental odors, when compared to healthy controls they generally are found to be equally or even less sensitive to odors as measured by objective psychophysical and electrophysiological measures of olfactory function. These studies point towards alterations in the cognitive processing of olfactory information as the major characteristic of IEI. Second, studies of the role of sensitivity and bias in olfactory and trigeminal chemosensory functioning indicate that nonsensory factors (e.g., attention, bias, personality) can dramatically alter the self-reported impact of exposure to volatile chemicals. Together, these general points suggest a perspective on IEI that views many symptoms of the disorder to primarily reflect the influence of nonsensory, cognitive processes on responses to environmental odors.

Evaluation of odor and sensory irritation thresholds for methyl isobutyl ketone in humans.

Odor and irritation sensitivity for methyl isobutyl ketone (MIBK) was evaluated by obtaining olfactory detection thresholds and irritation (lateralization) thresholds, as well as perceived odor intensity and irritation ratings for three predetermined concentrations of MIBK, acetone, and phenylethyl alcohol. Subsequently, perceived annoyance ratings for the three concentrations were measured for 25 of the 40 volunteers. The mean odor detection threshold for MIBK was 10 ppm, and mean lateralization threshold was 8874 ppm. Calculating the fifth percentile for lateralization thresholds revealed that 95% of the sample population did not experience sensory irritation at or below 1802 ppm. Thus, while odor thresholds were well below the current recommended exposure limits (50 ppm, threshold limit value; 75 ppm short-term exposure limit, American Conference of Governmental Industrial Hygienists), irritation thresholds were significantly higher. Odor and irritation intensity ratings for the chemicals increased with increasing concentrations and were higher for MIBK than for acetone. However, when the affective component of the irritation response (annoyance) was rated separately from the sensory component (perceived irritation), no significant differences were found between the irritancy of MIBK and acetone, suggesting that negative hedonic evaluations of MIBK (perhaps based on odor unfamiliarity) contributed to ratings of perceived irritation. These results validate coupling affective and sensory ratings to more effectively examine the human response to volatile stimuli. Results indicate that intranasal sensory irritation from MIBK will not be experienced at or near current exposure levels. Notably, the best predictors of perceived irritation to high concentrations of MIBK were those measures related to its odor, not to the threshold for sensory irritation, suggesting that negative responses to MIBK involve reactions to olfactory properties.

Histology of the gastroesophageal junction: an autopsy study.

Current diagnostic criteria for reflux disease and Barrett's esophagus are based on the belief that the gastroesophageal junction normally contains 2 cm of cardiac mucosa composed of mucous glands devoid of parietal cells. This autopsy study disproves this belief. Even when the entire circumference of the gastroesophageal junction is examined, pure cardiac mucosa was completely absent in 56% of patients. All patients had oxyntocardiac mucosa, in which glands contained a mixture of mucous and parietal cells. Cardiac and oxyntocardiac mucosae were present only in part of the circumference of the junction in 50% of patients. The measured maximum length of cardiac plus oxyntocardiac mucosa was less than 0.5 cm in 76% of patients. There was a tendency for the presence and extent of cardiac mucosa to increase with age. Cardiac mucosa at the junction is therefore frequently absent, has considerable individual variation, is very small in extent when present, is commonly absent from some part of the circumference of the junction, and increases in prevalence and length with age. These characteristics of cardiac mucosa make it highly unlikely that it is a normal structure. We develop the hypothesis that cardiac mucosa represents an early histologic manifestation of gastroesophageal reflux.

Development and clinical assessment of an artificial cornea.

Keratoprosthesis research has been a gradual, rather fragmentary process with advances being made by isolated groups of researchers. This has arisen partly because of poor funding in the area; research groups which have achieved commercial support have often had constraints upon the full disclosure of their findings. Despite these difficulties there has been real progress over the last decade by several independent groups. This article concentrates upon our own development of a hydrogel core-and-skirt keratoprosthesis, the Chirila KPro, in order to illustrate the scientific and clinical problems common to keratoprosthesis research. Pilot data from a clinical trial is presented and the priorities for future research are discussed.

Hydrophilic sponges based on 2-hydroxyethyl methacrylate: part VII: modulation of sponge characteristics by changes in reactivity and hydrophilicity of crosslinking agents.

Despite previous unsuccessful attempts to use hydrated poly(2-hydroxyethyl methacrylate) sponges as implantable biomaterials, recently these materials became important as peripheral components in an artificial cornea of the core-and-skirt design. The low mechanical strength of sponges prompted this study on possible improvement of tensile properties by the use of a variety of crosslinking agents. Three vinylic (dimethacrylates) and two allylic compounds were used at different concentrations (0.1 to 2% (mol)) as crosslinking agents in the production of sponges. Their influence on the mechanical properties, porous morphology and swelling behavior of resulting sponges was evaluated. The onset of phase separation during polymerization was also measured by visible spectrophotometry. The results suggested an inherent heterogeneity of sponges, i.e. pores of non-uniform size and structural inhomogeneities. While the effects of changes in the nature and concentration of crosslinking agents on the equilibrium water content of sponges were ambiguous, some of the mechanical properties, such as toughness and elasticity, were improved by crosslinking with allylic agents. Scanning electron microscopic examination suggested that the mechanical effect is related to the variation of size of the polymer particles constituting the sponge structure, which was proved to be dependent upon the onset of phase separation during polymerization.

Variance analysis in clinical pathways for total hip and knee joint arthroplasty.

Clinical pathways are being increasingly used for daily patient care. The pathways consist of a sequence of critical treatment events matched to the patient's recovery. Variance analysis identifies deviations from the pathway and can be used for quality improvement and clinical audit. The aim of this study is to analyse the variances from clinical pathways in two common elective orthopaedic operations. A prospective variance analysis was performed from the clinical pathways of all patients undergoing total hip and total knee arthroplasty over a 12 month period. Variances were categorised according to their source and then further divided into serious and non-serious variances. A total of 65 patients underwent total knee replacement during the study. Eleven serious variances were recorded in eight of these patients (12.3%) with a surprisingly high number of cardiac events. A total of 52 patients underwent total hip replacement with nine serious variances recorded in seven of these patients (13.5%). Clinical pathways can be used as a means of incorporating evidence-based medicine into clinical practice. Variance analysis of the pathways can be utilised as a process of quality control and to improve patient outcomes. Serious variances within this study were higher than anticipated.