ENT UK coronavirus disease 2019 adult tonsillitis and quinsy guidelines: translating guidance into practice.

OBJECTIVES: This study examined the uptake of ENT UK coronavirus disease 2019 adult tonsillitis and quinsy guidelines at our tertiary centre, and assessed perceived barriers to uptake. METHODS: A retrospective case series of tonsillitis and quinsy patients was analysed in two arms: before and after the introduction of new ENT UK management guidelines. A survey assessed perceptions and practice differences between ENT and emergency department doctors. RESULTS: Each study arm examined 82 patients. Following the introduction of new ENT UK guidelines, ENT clinicians demonstrated significant changes in practice, unlike their emergency department counterparts. Survey results from emergency department doctors highlighted a lack of appreciation of guideline change and identified barriers to guideline uptake. CONCLUSION: The introduction of new management guidelines for tonsillitis and quinsy patients during the pandemic resulted in disparate uptake within ENT and emergency department departments at the tertiary centre. Clearer dissemination to all affected clinicians is paramount for future rapidly introduced changes to practice, to ensure clinician safety.

A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Visual-motor contingency during symbol production contributes to short-term changes in the functional connectivity during symbol perception and long-term gains in symbol recognition.

Letter production relies on a tight coupling between motor movements and visual feedback-each stroke of the letter is visually experienced as it is produced. Experience with letter production leads to increases in functional connectivity, a measure of neural communication, among visual and motor brain systems and leads to gains in letter recognition in preliterate children. We hypothesized that the contingency between the motor and visual experiences of the written form during production would result in both effects. Twenty literate adults were trained on four sets of novel symbols over the course of one week. Each symbol set was trained through one of four training conditions: drawing with ink, drawing without ink, watching a handwritten symbol unfold as if being drawn, and watching a static handwritten symbol. Contingency of motor and visual experiences occurred in the drawing with ink condition. The motor and visual experiences were rendered non-contingent in each of the other three conditions by controlling for visual or motor experience. Participants were presented with the trained symbols during fMRI scanning at three time points: one pre-training, one post-training, and one after a week-long no-training delay. Recognition was tested after each training session and after the third scan. We found that the contingency between visual and motor experiences during production changed the pattern of functional connectivity among visual, motor, and auditory neural communities and resulted in better recognition performance at post-training than at pre-training. Recognition gains were maintained after the no-training delay, but the functional connections observed immediately after training returned to their pre-training baselines. Our results suggest that behaviors that couple sensory and motor systems result in temporary changes in neural communication during perception that may not directly support changes in recognition.

Platelet function testing in patients with post-operative tonsillectomy bleeding may be a useful early identifier of inherited platelet function disorders.

BACKGROUND: Post-tonsillectomy bleeding is the most frequent complication of tonsillectomy. Inherited platelet function disorders have an estimated prevalence of 1 per cent. Any association between post-tonsillectomy bleeds and undiagnosed inherited platelet function disorders has not been investigated before. OBJECTIVES: To assess the prevalence of inherited platelet function disorders in a cohort of post-tonsillectomy bleed patients. METHODS: An observational cohort study was conducted using hospital digital records. Platelet function analyser 100 ('PFA-100') closure time was tested on post-tonsillectomy bleed patients who presented to hospital. RESULTS: Between 2013 and 2017, 9 of 91 post-tonsillectomy bleed patients who underwent platelet function analyser 100 testing (9.89 per cent) had positive results. Five patients (5.49 per cent) had undiagnosed inherited platelet function disorders. Four patients had false positive results secondary to a non-steroidal anti-inflammatory drug effect (specificity of 95.3 per cent) proven by repeat testing six weeks later, off medication. The false negative rate was 0 per cent. CONCLUSION: The prevalence of inherited platelet function disorders in our post-tonsillectomy bleed cohort is five-fold higher than in the general population. Platelet function analyser 100 testing when patients present with a post-tonsillectomy bleed allows management of their inherited platelet function disorder.

Preclinical assessment of a new magnetic resonance-based technique for determining bone quality by characterization of trabecular microarchitecture.

The utility of HR-CT to study longitudinal changes in bone microarchitecture is limited by subject radiation exposure. Although MR is not subject to this limitation, it is limited both by patient movement that occurs during prolonged scanning at distal sites, and by the signal-to-noise ratio that is achievable for high-resolution images in a reasonable scan time at proximal sites. Recently, a novel MR-based technique, fine structure analysis (FSA) (Chase et al. Localised one-dimensional magnetic resonance spatial frequency spectroscopy. PCT/US2012/068284 2012, James and Chase Magnetic field gradient structure characteristic assessment using one-dimensional (1D) spatial frequency distribution analysis. 7932720 B2, 2011) has been developed which provides both high-resolution and fast scan times, but which generates at a designated set of spatial positions (voxels) a one-dimensional signal of spatial frequencies. Appendix 1 provides a brief introduction to FSA. This article describes an initial exploration of FSA for the rapid, non-invasive characterization of trabecular microarchitecture in a preclinical setting. For L4 vertebrae of sham and ovariectomized (OVX) rats, we compared FSA-generated metrics with those from CT datasets and from CT-derived histomorphometry parameters, trabecular number (Tb.N), bone volume density (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). OVX caused a reduction of the higher frequency structures that correspond to a denser trabecular lattice, while increasing the preponderance of lower frequency structures, which correspond to a more open lattice. As one example measure, the centroid of the FSA spectrum (which we refer to as fSAcB) showed strong correlation in the same region with CT-derived histomorphometry values: Tb.Sp: r -0.63, p < 0.001; Tb.N: r 0.71, p < 0.001; BV/TV: r 0.64, p < 0.001, Tb.Th: r 0.44, p < 0.05. Furthermore, we found a 17.5% reduction in fSAcB in OVX rats (p < 0.0001). In a longitudinal study, FSA showed that the age-related increase in higher frequency structures was abolished in OVX rats, being replaced with a 78-194% increase in lower frequency structures (2.4-2.8 objects/mm range), indicating a more sparse trabecular lattice (p < 0.05). The MR-based fine structure analysis enables high-resolution, radiation-free, rapid quantification of bone structures in one dimension (the specific point and direction being chosen by the clinician) of the spine.

Compartmental modelling of the pharmacokinetics of a breast cancer resistance protein.

A mathematical model for the pharmacokinetics of Hoechst 33342 following administration into a culture medium containing a population of transfected cells (HEK293 hBCRP) with a potent breast cancer resistance protein inhibitor, Fumitremorgin C (FTC), present is described. FTC is reported to almost completely annul resistance mediated by BCRP in vitro. This non-linear compartmental model has seven macroscopic sub-units, with 14 rate parameters. It describes the relationship between the concentration of Hoechst 33342 and FTC, initially spiked in the medium, and the observed change in fluorescence due to Hoechst 33342 binding to DNA. Structural identifiability analysis has been performed using two methods, one based on the similarity transformation/exhaustive modelling approach and the other based on the differential algebra approach. The analyses demonstrated that all models derived are uniquely identifiable for the experiments/observations available. A kinetic modelling software package, namely FACSIMILE (MPCA Software, UK), was used for parameter fitting and to obtain numerical solutions for the system equations. Model fits gave very good agreement with in vitro data provided by AstraZeneca across a variety of experimental scenarios.

Detection and classification of sensory information from acute spinal cord recordings.

One avenue of research for partial restoration of function following spinal cord injury is the use of neural prostheses, an example of which is functional electrical stimulation (FES) devices for motor functions. Neural prostheses may also be useful for the extraction of sensory information directly from the nervous system. We suggest the spinal cord as a possible site for the detection of peripheral sensory information from neural activity alone. Acute multichannel extracellular recordings were used to extract neural spike activity elicited from peripheral sensations from the spinal cords of rats. To test the recording method and classification potential, eight classes of sensory events were recorded consisting of electrical stimulation of seven locations on rat forepaws, and another class of data during which no stimulus was present. A dual-stage classification scheme using principal component analysis and k-Means clustering was devised to classify the sensory events during single trials. The eight tasks were correctly identified at a mean accuracy of 96%. Thus, we have shown the methodology to detect and classify peripheral sensory information from multichannel recordings of the spinal cord. These methods may be useful, for example, in a closed-loop FES for restoration of hand grasp.

An fMRI study of the selective activation of human extrastriate form vision areas by radial and concentric gratings.

The ventral form vision pathway of the primate brain comprises a sequence of areas that include V1, V2, V4 and the inferior temporal cortex (IT) [1]. Although contour extraction in the V1 area and responses to complex images, such as faces, in the IT have been studied extensively, much less is known about shape extraction at intermediate cortical levels such as V4. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate that the human V4 is more strongly activated by concentric and radial patterns than by conventional sinusoidal gratings. This is consistent with global pooling of local V1 orientations to extract concentric and radial shape information in V4. Furthermore, concentric patterns were found to be effective in activating the fusiform face area. These findings support recent psychophysical [2,3] and physiological [4,5] data indicating that analysis of concentric and radial structure represents an important aspect of processing at intermediate levels of form vision.

The effects of visual object priming on brain activation before and after recognition.

BACKGROUND: Recognizing an object is improved by recent experience with that object even if one cannot recall seeing the object. This perceptual facilitation as a result of previous experience is called priming. In neuroimaging studies, priming is often associated with a decrease in activation in brain regions involved in object recognition. It is thought that this occurs because priming causes a sharpening of object representations which leads to more efficient processing and, consequently, a reduction in neural activity. Recent evidence has suggested, however, that the apparent effect of priming on brain activation may vary as a function of whether the neural activity is measured before or after recognition has taken place. RESULTS: Using a gradual 'unmasking' technique, we presented primed and non-primed objects to subjects, and measured activation time courses using high-field functional magnetic resonance imaging (fMRI). As the objects were slowly revealed, but before recognition had occurred, activation increased from baseline level to a peak that corresponded in time to the subjects' behavioural recognition responses. The activation peak for primed objects occurred sooner than the peak for non-primed objects, and subjects responded sooner when presented with a primed object than with a non-primed object. During this pre-recognition phase, primed objects produced more activation than non-primed objects. After recognition, activation declined rapidly for both primed and non-primed objects, but now activation was lower for the primed objects. CONCLUSIONS: Priming did not produce a general decrease in activation in the brain regions involved in object recognition but, instead, produced a shift in the time of peak activation that corresponded to the shift in time seen in the subjects' behavioural recognition performance.

Anaesthetic management of a patient with erythropoietic protoporphyria for ventricular septal defect closure.

Erythropoietic protoporphyria (EPP) is due to a deficiency in ferrochelatase required for haem synthesis. We describe the anaesthetic management of a seven-year-old with EPP undergoing closure of a haemodynamically significant ventricular septal defect. Photosensitivity in EPP patients is triggered at wavelengths near 400 nm and light-excited porphyrins generate free radicals and singlet oxygen that lead to erythrocyte deformity and haemolysis. Stimuli that could trigger a porphyric crisis during anaesthesia and surgery were reduced by avoiding exposure to the sensitive 400 nm spectrum and using light sources covered with yellow acrylate filters in the operating room. Anaesthetic agents not previously associated with porphyric crisis were chosen. Whole blood priming of the extracorporeal circuit was performed to ensure adequate haemoglobin concentrations during the perioperative period.

Indications for pneumonectomy. Pneumonectomy for malignant disease.

The anatomic extent of a pulmonary malignancy usually dictates the need for pneumonectomy to achieve a complete resection. The requirement for a pneumonectomy can frequently be predicted by accurate clinical staging, but may also be required due to intraoperative findings relating to tumor invasion or nodal spread. Completion pneumonectomy is usually reserved for locally recurrent lung cancer or early to late complications following pulmonary resection. Malignant involvement of the carina frequently requires sleeve pneumonectomy.

Repetition priming and the time course of object recognition: an fMRI study.

We investigated the effects of repetition priming on the time course of recognition in several visual areas of the brain using fMRI. We slowed down recognition by gradually revealing the stimuli, in order to prolong the pre-recognition phase. Activation was lower for primed than for non-primed objects overall in both the occipitotemporal region (OTR) and the intraparietal region (IPR). A difference was found between primed and non-primed objects in the rate of increase of OTR activation. We concluded that the IPR, in addition to the OTR, was affected by repetition priming, and that this effect was different from that seen in the OTR.

Use of the internal mammary artery graft in Northern New England. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: There is evidence that patients who receive an internal mammary artery graft (IMA) during coronary artery bypass surgery have increased long-term survival. However, an IMA is not used in all patients. METHODS AND RESULTS: We studied the use of IMA grafts among 7944 patients undergoing initial, isolated coronary artery bypass surgery in Maine, New Hampshire, and Vermont from 1992 to 1995. Overall, the IMA graft was used in 82% of patients; of these, 97.2% had left IMA grafts. The use of the IMA graft varied considerably by patient and disease factors. Women received an IMA graft significantly less often (76% versus 85% in men, P<.01). Older patients (> or =75 years) were less likely to receive an IMA graft (67% versus 86%, P<.001). Smaller BSA was also associated with lower rates of IMA grafts in both sexes; however, men and women with BSA <1.8 m2 received an IMA graft at about the same rate. In general, more sick and more urgent patients had lower rates of IMA use. Patients with left ventricular ejection fraction <40% received an IMA less often than those with an ejection fraction > or =60% (77% versus 85%, P<.01). Patients with a greater number of diseased coronary vessels received an IMA more often (one, 78%; two, 82%; three, 85%). IMA use varied significantly by priority of surgery, with elective patients receiving an IMA 88% of the time, urgent 83%, and emergent 51% (Ptrend<.01). The use of the IMA graft varied from 42% to 95% among individual surgeons. Surgeons were consistent in their patterns of IMA graft use for specific risk groups. All surgeons had lower rates of IMA use among older patients, lower rates of IMA among women, and lower rates of IMA use among emergent or urgent patients. However, "low-use" surgeons had consistently lower rates of use within these patient groups. The overall rate of IMA graft use increased from 76% in 1992 to 86% in 1995 (Ptrend<.001). IMA graft use increased in all five centers and in all patient subgroups. The largest increases in use were seen among women (from 69% to 83%), among patients older than 75 years (from 55% to 75%), and in emergent patients (from 40% to 72%). CONCLUSIONS: This regional prospective study of IMA graft use in initial coronary artery bypass surgery describes substantial variability in patient groups receiving an IMA as well as increasing IMA graft use over time. It also suggests that the practice patterns of surgeons are an important determinant of IMA use. These data indicate that even more patients could benefit from the use of this technique.

Thin film high temperature superconducting RF coils for low field MRI.

We have built and tested a thin-film high temperature superconducting (HTS) surface coil for MRI at 0.064T. When placed as close as possible to a conductive sample, the 6.7-cm outer diameter HTS coil had a measured signal-to-noise ratio (SNR) 1.8 times higher than a room temperature copper coil of similar size and location. Our results predict that in some cases, SNR gains of about a factor of 2 can be attained in low-field MRI systems by substituting HTS surface coils for copper coils.

Urokinase inhibits HL-60 cell proliferation in vitro.

The binding of urokinase-type plasminogen activator (u-PA) to its receptor (u-PA-R) is required for morphological and functional maturation during monocyte differentiation of the promyelocytic leukaemia line HL-60. This paper reports that monocyte differentiation of HL-60 cells induced by 1,25 dihydroxyvitamin D2 (vitamin D2) results in a marked increase in expression of u-PA and u-PA-R. This increase in u-PA expression is of greater magnitude than is observed after culture with interferon-gamma (IFN gamma), another potent inducer of monocytic differentiation. Dimethyl sulphoxide (DMSO), an agent that induces granulocytic differentiation, also increased expression of u-PA. However, culture with the granulocyte-inducing all-trans retinoic acid (RA) did not induce an increase in surface expression of u-PA or u-PA-R. The vitamin D2-induced increase in cell-surface u-PA was not coincident with an increase in steady-state levels of u-PA mRNA, suggesting that intracellular stores of this protein, translational or post-translational mechanisms of regulation, or some other regulatory mechanism may be responsible for the increase in u-PA during differentiation. To ascertain an association between the increased expression of cell-surface u-PA and reduced proliferation that accompanies differentiation, the effect of u-PA on cellular proliferation of HL-60 cells was measured. Both pro-u-PA (whole molecule) and fragments of u-PA that retained receptor-binding capability caused a marked inhibition of HL-60 proliferation in the absence of vitamin D2.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of collagenase and stromelysin gene expression by mechanical injury in a vascular smooth muscle-derived cell line.

We describe a novel system for studying the production of matrix metalloproteinases types I and III (collagenase and stromelysin) by a vascular smooth muscle cell line (Rb-1 cells) in response to mechanical injury. Highly confluent Rb-1 cells are disrupted by passing a plastic comb around the plate to clear a series of circumferential paths, which are bordered by two ridges of displaced cells. Over the next 24 hours, cells migrate into the cleared areas. Northern blot analysis demonstrates the accumulation of mRNAs for collagenase and stromelysin during this process, although they are undetectable prior to injury. Cotreatment with all-trans-retinoic acid (10(-6) M) markedly decreases the level of mRNAs induced by injury, whereas dexamethasone (10(-7) M) causes only a slight reduction. In situ hybridization studies for stromelysin mRNA and immunohistochemical staining for collagenase protein on plates of injured cells showed the highest levels of stromelysin mRNA in cells in the ridges left by the injury; lower levels were observed in some cells migrating into the clear region. The same pattern of expression was observed when cells were stained with antiserum to collagenase protein. Nuclear run-on assays demonstrated increases in transcription of stromelysin and collagenase genes following injury. Transient transfection of cells with a vector containing the luciferase gene driven by a wild-type promoter comprising 1.8 kb of the 5'-flanking region of the rabbit collagenase gene showed increased activity associated with injury. We conclude that: (1) mechanical injury is associated with induction of mRNAs for the metalloproteinases collagenase and stromelysin, (2) retinoic acid effectively antagonizes this responses, and (3) the increase in steady-state mRNA levels is, at least in part, transcriptionally mediated. Thus our data suggest a role for mechanical forces in initiating the changes in gene expression in vascular smooth muscle cells following arterial injury in vivo.

The eyespot of Euglena gracilis: a microspectrophotometric study.

The eyespots in cells of streptomycin-bleached strains and of dark-grown cultures of Euglena gracilis, were examined by means of fluorescence microscopy and microspectrophotometry. When viewed with light in the region of 380-500 nm, the stigma appeared as a dark spot. Adjacent to this was a second spot, not seen with white light, but which was seen to fluoresce when excited with radiation at 370 +/- 20 nm. This fluorescence proved to be polarized in contrast to other fluorescing bodies in the cell. The absorption curves, obtained by microspectrophotometry of individual eyespots, were found to consist of two spectral maxima, an A-band in the blue and a B-band in the green. Unlike the A-band, the B-band provided evidence of originating from an anisotropic structure. Relating these data to literature findings, we conclude that the B-band is the absorbance of a pigment in the quasi-crystalline paraflagellar body and the A-band perhaps a pigment in the orange-red stigma. The spectrum of the B-band does not appear to be that of a flavoprotein or of a free carotenoid but its resemblance to the spectrum of rhodopsin is significant in relation to published data for the Chlamydomonas eyespot that suggests the presence of a rhodopsin-like pigment as the photosensitive system responsible for phototaxis in this alga.

The eyespot of Chlamydomonas reinhardtii: a comparative microspectrophotometric study.

The eyespot of Chlamydomonas reinhardtii is believed to utilize a rhodopsin-like pigment in its responses to light. This paper examines its eyespot by means of microspectrophotometry with the finding of an absorption spectrum with two bands, an A-band in the blue, and a B-band in the green. This spectrum is identical to that previously recorded from the eyespot of Euglena gracilis. As with Euglena the B-band was found to have dichroic character and its spectrum was similar to the absorption curve of rhodopsin. This A-B-spectrum was always recorded from a single granule in each cell. It is concluded that both E. gracilis and C. reinhardtii may utilize a rhodopsin-like pigment as the photopigment associated with the eyespot response to light. In both these algae a few particles in each cell were found whose spectra consisted of two other bands, C and D, blue- and red-shifted, respectively, relative to the eyespot A-B-bands. There is some reason to believe that the C-D-granules may also be involved in certain light-controlled activities of the cells.