Validation of the British Society of Thoracic Imaging guidelines for COVID-19 chest radiograph reporting.

AIM: To validate the British Society of Thoracic Imaging issued guidelines for the categorisation of chest radiographs for coronavirus disease 2019 (COVID-19) reporting regarding reproducibility amongst radiologists and diagnostic performance. MATERIALS AND METHODS: Chest radiographs from 50 patients with COVID-19, and 50 control patients with symptoms consistent with COVID-19 from prior to the emergence of the novel coronavirus were assessed by seven consultant radiologists with regards to the British Society of Thoracic Imaging guidelines. RESULTS: The findings show excellent specificity (100%) and moderate sensitivity (44%) for guideline-defined Classic/Probable COVID-19, and substantial interobserver agreement (Fleiss' k=0.61). Fair agreement was observed for the "Indeterminate for COVID-19" (k=0.23), and "Non-COVID-19" (k=0.37) categories; furthermore, the sensitivity (0.26 and 0.14 respectively) and specificity (0.76, 0.80) of these categories for COVID-19 were not significantly different (McNemar's test p=0.18 and p=0.67). CONCLUSION: An amalgamation of the categories of "Indeterminate for COVID-19" and "Non-COVID-19" into a single "not classic of COVID-19" classification would improve interobserver agreement, encompass patients with a similar probability of COVID-19, and remove the possibility of labelling patients with COVID-19 as "Non-COVID-19", which is the presenting radiographic appearance in a significant minority (14%) of patients.

Preliminary analysis of the FAM174A gene suggests it lacks a strong association with equine metabolic syndrome in ponies.

Equine metabolic syndrome (EMS) describes a group of risk factors, including obesity and insulin dysregulation (hyperinsulinemia and/or insulin resistance), that can lead to the development of the debilitating hoof disease laminitis. Although the underlying mechanisms of EMS are not fully understood, a genetic component has been reported, and an 11 guanine polymorphism located at the FAM174A gene has been identified as a risk locus for the syndrome in Arabian horses. To examine associations between the FAM174A risk allele and the clinical signs of EMS, the allele was examined in an Australian cohort of ponies (n = 20) with known metabolic status. The 11 guanine polymorphism was identified in only 3 of 13 ponies with EMS, and no significant association could be made between the risk loci and morphometric measurements associated with obesity (BCS [P = 0.21], cresty neck score [P = 0.58], basal triglyceride concentration [P = 0.85], and adiponectin concentration [P = 0.48]), or insulin dysregulation (insulin dysregulation status [P = 0.35] and serum insulin concentration during an oral glucose test [P = 0.44]). These results suggest that the FAM174A 11 guanine homopolymer allele is unlikely to be a singular key gene polymorphism associated with EMS in ponies. However, due to the small number of ponies identified with the polymorphism, further study of the FAM174A risk allele in a larger cohort of horses and ponies of uniform breed would be useful.

Variations in the MRI appearance of the insertion of the tendon of subscapularis.

Standard anatomical textbooks describe the insertion of the subscapularis tendon on to the lesser tuberosity of the humerus. The transverse humeral ligament is also described at this level, as a band of tissue attached to the greater and lesser tuberosities, overlying the long tendon of biceps as it emerges from the capsule of the shoulder joint. The shoulder is a notorious site for anatomical variation but until recently little has been published with regard to the tendon of subscapularis. In this study, we illustrate that considerable variation in the insertion site of the tendon of subscapularis can be demonstrated using magnetic resonance imaging and that only 20% conform to the classic textbook description. In addition, a distinct transverse humeral ligament was identifiable in only a minority of shoulders examined (36%).

Transverse humeral ligament: does it exist?

The insertion of the tendon of subscapularis is accepted as being on the lesser tubercle of the humerus. The transverse humeral ligament (THL) is described as a distinct entity in most textbooks, overlying the long tendon of biceps as it emerges from the capsule of the shoulder joint. In this study, we dissected 85 embalmed shoulders to clarify the anatomy of the THL and variation in the insertion of the tendon of subscapularis. In all specimens no distinct THL could be identified, but in every shoulder a fibrous expansion arose from the posterior lamina of the tendon of pectoralis major overlying the long tendon of biceps. In 86% of shoulders, fibres from the tendon of subscapularis passed over the long tendon of biceps within this fibrous expansion and inserted on to the greater tubercle of the humerus where one would expect to find the THL. In 33% of dissections, fibres from the tendon of subscapularis lay deep to the long tendon of biceps, inserting either into the bicipital groove or on to the greater tubercle. In only 8% of cases did the tendon of subscapularis insert exclusively on to the lesser tubercle. We conclude that the THL does not exist as a separate entity. We suggest that in the majority of cases, the structure overlying the long tendon of biceps as it emerges from the capsule of the shoulder joint consists of tendinous fibres from subscapularis, contained within a fibrous expansion derived from the posterior lamina of the tendon of pectoralis major. In the minority of shoulders, where the tendon of subscapularis inserts exclusively on to the lesser tubercle, we hypothesise that this fibrous expansion acts as a retinaculum preventing the long tendon of biceps from "bowstringing."

Spatial mapping of the brachial plexus using three-dimensional ultrasound.

Imaging of the brachial plexus with MRI and standard two-dimensional (2D) ultrasound has been reported, and 2D ultrasound-guided regional anaesthetic block is an established technique. The aim of this study was to map the orientation of the brachial plexus in relation to the first rib, carotid and subclavian arteries, using three-dimensional (3D) ultrasound. A free-hand optically tracked 3D ultrasound system was used with a 12 MHz transducer. 10 healthy volunteers underwent 3D ultrasound of the neck. From the 3D ultrasound data sets, the outlines of the brachial plexus, subclavian artery and first rib were manually segmented. A surface was interpolated from the series of outlines to produce a spatially orientated 3D reconstruction of the brachial plexus. The brachial plexus could be mapped in all volunteers, although a variation in image resolution between individuals existed. Anatomical variations were demonstrated between the 10 volunteers; the most notable and clinically relevant was the alignment of the plexus divisions. 3D reconstructions illustrated the plexus, changing its orientation from a vertical alignment in the interscalene region to a more horizontal alignment in the supraclavicular fossa. Spatial mapping of the brachial plexus is possible with 3D ultrasound using the subclavian artery and first rib as landmarks. There is a deviation from the conventionally described anatomy and this may have implications for the administration of regional anaesthesia.

3D reconstruction of the skeletal anatomy of the normal neonatal foot using 3D ultrasound.

Currently imaging plays a limited role in the assessment of the neonate with a foot deformity. The aim of this study was to establish a technique for examining the neonatal foot with three-dimensional ultrasound (3D US). 3D US was attempted on the normal feet of 20 infants (9 male, 11 female) under 6 weeks old (range 35-41 days). The data sets were obtained whilst the infants were feeding or asleep to minimize movement artefact. A high-resolution optically tracked freehand 3D US system (Diasus, 16 MHz transducer) was used with Stradx software to acquire and analyse the data sets. Manual segmentation of the non-ossified tarsi from the data sets was performed. Five infants were too restless to be examined. 107 data sets were recorded from 22 feet of the remaining 15 infants. 21 of the data sets were discarded due to movement artefact. 86 were suitable for manual segmentation. Surface interpolation of the segmented data sets produced surface rendered reconstructions illustrating the complex 3D anatomy of the foot. This new technique may offer a method of examining the deformed foot, e.g. congenital talipes equinovarus.

Two- and three-dimensional ultrasound in the development of a needle-free injection system.

Ultrasound was used to assess a needle-free injection device for both intradermal and subcutaneous injections. The aim of this study was, first, to differentiate intradermal from subcutaneous injections, both in vivo and in vitro using 2D ultrasound, and second, to quantify the amount of injectate that actually arrives within the dermis or subcutaneous tissues using volume measurements derived from high-resolution 3D ultrasound data sets, using a freehand system (Stradx), developed by the Cambridge University Departments of Engineering and Radiology. For the in vitro study the devices were filled with dye and injected into a pig preparation. The injection site was examined with high-resolution ultrasound and subsequently dissected to locate the injected dye with respect to the dermis. For the in vivo study, 8 volunteers received needle-free injections of normal saline. High-resolution 2D images and 3D data sets were obtained of the injected sites. Proprioceptive information for the 3D data sets was produced using an optically tracked freehand system. Segmentation of the 3D data sets gave an estimation of the volume of injected material (injectate) within the dermis. The results demonstrated that 2D ultrasound could identify the location of the injectate in the in vitro experiments and successfully distinguished an intradermal from a subcutaneous injection. In the in vivo study, 2D ultrasound clearly demonstrated the injectate location within the volunteers' dermis but was less able to demonstrate the dispersion of injectate within the subcutaneous tissues.

Processing and visualizing three-dimensional ultrasound data.

This paper describes techniques for the visualization and processing of three-dimensional (3D) ultrasound data. The nature of such data demands specialized algorithms, which differ from those employed for other medical imaging modalities. In this paper, the emphasis is placed on generic processing techniques, which are relevant across a wide range of 3D ultrasound application domains.

Requests for body computed tomography: increasing workload, increasing indications and increasing age.

Increasing numbers of increasingly elderly patients were being examined in our Body CT department. At the same time, some of our clinical colleagues perceived that their patients might be discriminated against on the basis of their age when allocating CT time. We therefore studied the population trends in our department over a 10-year period. The ages of patients attending the Body CT department were collected from the hospital's computer information system from 1995 to 2000 and from handwritten logbooks for the months of September 1988 and 1998. Comparison was made with population trends within the hospital and local demographic data. There has been an average increase of 11% per annum in the number of examinations performed in the Body CT unit. The average age of patients examined increased from 52.7 years in 1988 to 58.9 years in 1998. The largest increase occurred in the over 75-year population (18% rise per annum). Hospital and local demographic population profiles changed little during the same period. We are performing increasing numbers of body CT examinations on increasingly elderly patients. This is probably due to an increased willingness to investigate and treat elderly patients, rather than changes in the local population. There is no evidence of a general discriminatory policy on the basis of age.

The accuracy of antenatal ultrasound in the detection of facial clefts in a low-risk screening population.

OBJECTIVES: To evaluate the accuracy of prenatal ultrasound in the detection of facial clefts in a low-risk screening population and to report on the outcome of these pregnancies. DESIGN: We retrospectively reviewed antenatal ultrasound records from the obstetric ultrasound department, postnatal records from the regional craniofacial unit and autopsy reports of fetuses over 16 weeks' gestational age from the regional pathology department over a 5-year period (1993-97). Cross-referencing between the three data sets identified all cases of facial clefts. RESULTS: Out of 23 577 live and still births, 30 had facial clefts; four were excluded from the study. Of the remaining 26 cases, 10 had associated major anomalies. There were 19 live births and seven terminations. Six of the seven terminations had other major abnormalities. Our detection rate for cleft lip and palate was 93% and the detection rate for isolated cleft palate was 22%. Isolated cleft lip was detected in 67% of cases. The overall detection rate for facial clefts was 65%. CONCLUSION: From our results and a review of the literature it is clear that before standards can be set we need to define which facial clefts are sonographically demonstrable. Our data provide information for effective counseling and setting of standards for clinical practice.

Gamma-hydroxybutyrate receptor function studied by the modulation of nitric oxide synthase activity in rat frontal cortex punches.

Previous results have shown that stimulation of the gamma-hydroxybutyrate (GHB) receptor modulates Ca2+ channel permeability in cell cultures. In order to confirm this result, we investigated the consequence of GHB receptor stimulation on nitric oxide synthase (NOS) activity in rat brain cortical punches rich in GHB receptors. The stimulation of these receptors by increasing amounts of GHB induced a progressive decrease in NOS activity. However, for GHB doses above 10 microM, this reduction was progressively lost, either after receptor desensitization or after stimulation of an additional class of GHB receptor having lower affinity. The effect of GHB was reproduced by the GHB receptor agonist NCS-356 and blocked by the GHB receptor antagonist NCS-382. The GHB-induced effect on Ca2+ movement was additive to those produced by veratrine, indicating that GHB modulates a specific Ca2+ conductance, which explains the modification in NOS activity and the increase in cyclic guanosine monophosphate levels previously reported.

Lysosomal lipid accumulation from oxidized low density lipoprotein is correlated with hypertrophy of the Golgi apparatus and trans-Golgi network.

Lipid accumulation within macrophages is a major sequelae of atherosclerosis. Much of this lipid accumulation occurs within large, swollen lysosomes. We analyzed lipid accumulation in cultured macrophages using oxidized or acetylated low density lipoprotein (LDL) as the loading agent. Pigeon macrophages incubated for 48 h with mildly oxidized pigeon LDL (TBARS = 5-10 nmol/mg protein) showed significant increases in cellular cholesterol compared with untreated controls. Forty-eight percent of the increased cholesterol occurred as unesterified cholesterol. Treated cells had lipid-swollen lysosomes similar to those of atherosclerotic foam cells. The increase in lysosomal lipid was accompanied (correlation coefficient of 0.96) by increases in acid phosphatase staining cisternae of the Golgi and trans-Golgi network (TGN). THP-1 macrophages incubated with oxidized LDL showed similar lysosomal loading and Golgi/TGN hypertrophy. In contrast, macrophages incubated with acetylated LDL accumulated significant amounts of cholesterol but the increase occurred as cholesteryl ester (81% in pigeons) within cytoplasmic droplets and there was no associated increase in acid phosphatase-containing cisternae of Golgi or TGN. The correlation in both pigeon and THP-1 macrophages of oxidized LDL-induced lysosomal lipid accumulation and Golgi hypertrophy suggests a linkage of these two phenomena. This implicates intracellular membrane trafficking as a possible defect in foam cells of the atherosclerotic lesion.

Why tryptophan hydroxylase is difficult to purify: a reactive oxygen-derived species-mediated phenomenon that may be implicated in human pathology.

1. Attempts and apparently successful procedures to obtain reasonable quantities of electrophoretically homogenous mammalian brain-derived tryptophan hydroxylase, (TPH), have been described, starting in the early 1970s. This work has been carried out with the primary objective to obtain specific antisera to this enzyme to map out serotonergic pathways in the nervous system. 2. By using a multitude of techniques, antisera have indeed been fabricated and employed. However, it is doubtful if pure, native TPH has ever been produced. Indeed, there is strong evidence that more than one isoform of TPH exists in the rat brain. Thus, these antisera are probably directed against TPH-derived polypeptides and not the holoenzyme(s). 3. The difficulty in the purification of TPH lies not only in its subjectivity to proteolysis, but more importantly in its probable capacity to produce superoxide leading to hydrogen perioxide formation. This, in turn, may undergo Fenton chemistry with iron at the active site of the protein to produce hydroxyl radicals that directly attack and destroy the enzyme molecule. Evidence for such a mechanism is presented together with possible protocols that might be used to produce pure stable holo TPH(s). 4. It is hypothesized that similar oxidative events may take place in vivo under certain conditions leading to pathological results. Strategies to block these events are suggested.

Are the reactive oxygen-derived species (ROS) interactive properties of the many therapeutic drugs from various categories pertinent to their beneficial effects?

Many pathologic states are known to involve the generation of reactive oxygen species, (ROS). It is not known at present to what extent these phenomena are due to ROS formation, or if their formation is a result of the disease. Many therapeutic drugs either scavenge ROS or inhibit their formation. The purpose of this review is to match the drugs used for certain diseases with their anti-ROS actions. This attempted correlation is made to try to give an answer to the title question.

What is the role of the gamma-hydroxybutyrate receptor?

A possible functional role for endogenous gamma-hydroxybutyrate has been disputed. However, there are receptor sites for this molecule, which are highly enriched in the synaptosomal membrane fraction in the rat brain and are functionally linked to a guanosine triphosphate-binding protein. These data suggest that they play a neurological role. The binding sites recognize some drug molecules that bear no structural similarity to gamma-hydroxybutyrate. Recent experimental evidence indicates the existence of endogenous hydrophobic ligands. As a minor brain metabolite directly or indirectly involved in scavenging oxygen-derived free radicals, gamma-hydroxybutyrate demonstrates similarities with melatonin. The gamma-hydroxybutyrate receptor is compared to the cannabis receptor, for which an endogenous hydrophobic ligand has been identified. Structurally similar molecules to this ligand are believed to be implicated in the sleep process. As gamma-hydroxybutyrate itself can induce sleep, a search amongst these molecules as possible ligands for the gamma-hydroxybutyrate receptor might be enlightening.

Kinetic characterisation and solubilisation of gamma-hydroxybutyrate receptors from rat brain.

The solubilisation of the gamma-hydroxybutyrate (GHB) receptors from rat brain membranes was undertaken as the first step for their molecular characterisation and purification. Treatment of crude brain membranes with high concentrations of NaCl and Triton X-100 resulted in solubilisation of proteins which retain specific GHB binding activity. Ionic detergents do not solubilise and/or inactivate the receptors. Measurements of kinetic parameters of GHB binding showed that the solubilised receptor, in the presence of detergent, exhibited a reduction of affinity for GHB and its endogenous brain analogue trans-4-hydroxycrotonate (T-HCA). The membrane protein extract, submitted to chromatography by gel filtration, showed a single peak of protein with [3H]GHB binding activity. Association and dissociation constants of GHB for its membrane binding site were in accordance with the Kd determined by the Scatchard method.