Abdominal Aortic Aneurysm Diameters: A Study on the Discrepancy between Inner to Inner and Outer to Outer Measurements.

INTRODUCTION: The NHS Abdominal Aortic Aneurysm Screening Programme (NAAASP) uses the maximal anterior to posterior (AP) inner-to-inner (ITI) wall diameter in sizing aortic dimensions when screening with ultrasound. It is recognised that ITI measurements are smaller than outer-to-outer (OTO) measurements, and the primary aim was to calculate the absolute difference in AP ITI and OTO measurements across varying aortic diameters. The secondary aim was to estimate the potential number of patients lost from the screening programme. METHODS: Since April 2012, patients outside the screening programme that undergo ultrasound of abdominal aortas have their ITI and OTO measurements recorded. These measurements were compared retrospectively and analysed for variability at threshold sizes of AAAs. RESULTS: From May 2012 to October 2013, 452 abdominal aortic ultransound scans recorded both ITI and OTO measurements. The majority (81%) were performed on men with the mean age of 78 years. The mean difference between ITI and OTO measurements was 4.21 mm (p < .001). There was no difference between the genders. Thresholds were created for analysis between different ITI and OTO aortic diameters; these were <3 cm, 3.1-4 cm, 4.1-5 cm, and >5 cm. There was no significant difference between the means at each threshold size for ITI diameter (p = .758). In the first 2 years from April 2012, 15,447 men underwent screening.Of these, 177 (1.14%) had sub-threshold ITI aortic diameters between 2.6 cm and 2.9 cm. This would upscale to 5,316 men nationally. CONCLUSION: We have demonstrated a consistent and significant 4mm difference between ITI and OTO diameters in live scanning. Lowering the threshold for entry into a surveillance AAAs to an ITI diameter of 26mm rather than the current 30 mm is advocated. An alternative cost-effective way is to rescreen this small sub-group at 5 or 7 years.

Cell cytoskeletal changes effected by static compressive stress lead to changes in the contractile properties of tissue regenerative collagen membranes.

Static compressive stress can influence the matrix, which subsequently affects cell behaviour and the cell's ability to further transform the matrix. This study aimed to assess response to static compressive stress at different stages of osteoblast differentiation and assess the cell cytoskeleton's role as a conduit of matrix-derived stimuli. Mouse bone marrow mesenchymal stem cells (MSCs) (D1 ORL UVA), osteoblastic cells (MC3T3-E1) and post-osteoblast/pre-osteocyte-like cells (MLO-A5) were seeded in hydrated and compressed collagen gels. Contraction was quantified macroscopically, and cell morphology, survival, differentiation and mineralisation assessed using confocal microscopy, alamarBlue® assay, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and histological stains, respectively. Confocal microscopy demonstrated cell shape changes and favourable microfilament organisation with static compressive stress of the collagen matrix; furthermore, cell survival was greater compared to the hydrated gels. The stage of osteoblast differentiation determined the degree of matrix contraction, with MSCs demonstrating the greatest amount. Introduction of microfilament disrupting inhibitors confirmed that pre-stress and tensegrity forces were under the influence of gel density, and there was increased survival and differentiation of the cells within the compressed collagen compared to the hydrated collagen. There was also relative stiffening and differentiation with time of the compressed cell-seeded collagen, allowing for greater manipulation. In conclusion, the combined collagen chemistry and increased density of the microenvironment can promote upregulation of osteogenic genes and mineralisation; MSCs can facilitate matrix contraction to form an engineered membrane with the potential to serve as a 'pseudo-periosteum' in the regeneration of bone defects.

The influence of a bisphosphonate on bone generation determined using a chick-femur model.

AIM: To determine the direct influence of a bisphosphonate (pamidronate) delivered by one of two carriers, on bone generation in chick-femurs supported by chick egg chorio-allantoic membranes. METHODOLOGY: Twenty chick femurs freshly harvested from fertilized eggs were randomly allocated to two groups: (i) Affi-Gel blue bead carrier (n=10); and (ii) hydroxyapatite bead carrier (n=10). The femurs in each group were further randomly divided into control (n=4) and experimental (n=6) subgroups. Carriers charged with PBS solution or 0.1 M pamidronate were delivered into the bone marrow of each femur at its mid-portion through a needle puncture. Each femur was then grafted onto the chorio-allantoic membrane of a chick egg and incubated for 7 days. Each experimental and control subgroup femur yielded four histological sections at the puncture site, constituting the test and inter-bone controls. In addition, two histological sections were also obtained from 400 to 450 µm away from each end of the experimental puncture site to act as the intra-bone controls. Bone generation was quantified and the ratio of cross-sectional area of bone marrow to circumference of bone (outcome measure) was determined using a software package, Image-Pro(®) Plus. The data were analysed using Mann-Whitney tests and Wilcoxon signed rank tests. RESULTS: The outcome ratio in the test group was significantly (P<0.001) smaller than both the inter-bone and intra-bone control groups. There was evidence of increased bone formation directly over the pamidronate-charged carriers. CONCLUSIONS: The test model established that pamidronate had a positive effect on bone generation over a period of 7 days, regardless of the carrier type.

Dense collagen matrix accelerates osteogenic differentiation and rescues the apoptotic response to MMP inhibition.

Bone is distinguished from other tissues by its mechanical properties, in particular stiffness. However, we know little of how osteoblasts react to the stiffness of their microenvironment; in this study we describe their response to a dense (>10 wt.%) collagenous 3D environment. Primary pre-osteoblasts were seeded within a novel form of native collagen, dense collagen, and cultured for up to 14 days in the presence and absence of osteogenic supplements: analysis was via Q-PCR, histology, fluorescent in situ zymography, MMP loss-of-function and tensile testing. Differentiation as measured through the up-regulation of Bsp (247-fold), Alp (14.2-fold), Col1A1 (4.5-fold), Mmp-13 (8.0-fold) and Runx2 (1.2-fold) transcripts was greatly accelerated compared to 2D plastic at 7 and 14 days in the same medium. The scale of this enhancement was confirmed through the use of growth factor stimulation on 2D via the addition of BMP-6 and the Hedgehog agonist purmorphamine. In concert, these molecules were capable of the same level of osteo-induction (measured by Bsp and Alp expression) as the dense collagen alone. Mineralisation was initially localised to remodelled pericellular regions, but by 14 days embedded cells were discernible within regions of apatite (confirmed by MicroRaman). Tensile testing of the matrices showed that this had resulted in a significant increase in Young's modulus at low strain values, consistent with a stiffening of the matrix. To determine the need for matrix remodelling in the mineralisation event the broad spectrum MMP Inhibitor Ilomastat was used. It was found that in its presence mineralisation could still occur (though serum-specific) and the apoptosis associated with MMP inhibition in hydrated collagen gels was abrogated. Analysis of gene expression indicated that this was due to the up-regulation of Mmp-13 in the presence of Ilomastat in dense collagen (400-fold), demonstrating a powerful feedback loop and a potential mechanism for the rescue from apoptosis. Osteoid-like matrix (dense collagen) is therefore a potent stimulant of osteoblast differentiation in vitro and provides an environment that enables survival and differentiation in the presence of MMP inhibition.

The influence of military threats on the design and use of the Royal Naval Hospital Haslar.

The twin demands of the medical and security requirements influenced the original design of RNH Haslar. Over time the structure was altered to accommodate changes in the military threat and these changes can be identified from original plans and the extant structures. The use of spatial analysis, through the use of justified access graphs, can provide insights into the way the building was used and how it influenced the relationships between the staff and the patients.

Expression of the transcription factor slug correlates with growth of the limb bud and is regulated by FGF-4 and retinoic acid.

The slug gene encodes a zinc finger transcription factor expressed by neural crest cells (Nieto et al., Science 264: 835-839, 1994) and by certain non-crest derived mesenchymal cell populations, such as lateral mesoderm and sclerotome (Mayor et al., Development 121: 767-777, 1995; Buxton et al., Dev. Biol. 183: 150-165, 1997). We report here that slug is also expressed in developing chick limbs. The slug expression domain in the limb bud expands from posterior to anterior and marks cells that are predominantly destined to become chondrocytes but have not yet differentiated. Its expression is maintained in connective tissue, but is never observed in the premuscle masses. We show that removal of the apical ectodermal ridge results in loss of slug expression which can be arrested by the addition of an FGF-4 bead. Retinoic acid bead implants lead to down-regulation of slug expression, again accompanied by abolition of limb outgrowth. Dual bead implants demonstrate antagonism between these two factors, suggesting that a localized antagonistic effect between endogenous RA and FGF-4 on slug expression underlies the molecular mechanism controlling the transition between undifferentiated and differentiated state during normal limb development. The fact that slug expression pattern correlates with areas of growth in the limb, and is maintained by FGF-4 and down-regulated by retinoic acid, indicates that slug-expressing cells play a crucial role in growth and patterning of the chick limb. We propose that slug expression provides the best correlation to date between a molecular marker and the physical concept of the progress zone, defined as "a labile region where new positional values are successively engendered in the course of growth" (Summerbell et al., Nature 244: 492-496, 1973).

Thorotrast associated nodular regenerative hyperplasia of the liver.

A case of nodular regenerative hyperplasia (NRH) of the liver is described in association with exposure to the radiographic contrast medium Thorotrast. This is the first case in which the pathological findings have been fully documented. It is suggested that NRH may have developed through Thorotrast induced damage to portal vein radicles.

Sensitivity to sternotomy wires may cause postoperative pruritus.

An eczematous eruption developed on the anterior chest of a 58-year-old woman with known nickel sensitivity after the insertion of nickel-containing sternotomy wires. Her wound was revised with removal of the wires to give immediate and sustained relief from the itch. The electron microscopy and parasternal biopsy histology demonstrating a sarcoidal reaction are discussed.

Percutaneous cervical cordotomy: a review of 181 operations on 146 patients with a study on the location of "pain fibers" in the C-2 spinal cord segment of 29 cases.

The authors present a review of 146 patients who underwent 181 percutaneous cervical cordotomies for intractable pain. In addition, an anatomical-clinical correlation was carried out for 29 of these patients. It was found that the fibers subserving pain sensation in the C-2 segment lie in the anterolateral funiculus between the level of the denticulate ligament and a line drawn perpendicularly from the medial angle of the ventral gray-matter horn to the surface of the cord. The best analgesic results have been obtained by creating lesions that extend 5.0 mm deep to the surface of the cord and destroy about 20% of the hemicord. There is a somatotopic organization with sacral fibers running ventromedially and cervical fibers running dorsolaterally. The authors believe that the ascending fibers subserving the distinct sensations of pain induced by tissue damage and pinprick, although mixed (overlapping) in the anterolateral funiculus of the spinal cord, are physiologically distinct from one another. Whereas some cordotomies, both in the current series and as reported in the literature, may affect these functions differentially, optimum pain relief seems to be obtained only when pinprick sensation is also abolished in the affected segments. Evoked pain sensation is not abolished by cordotomy, but its threshold is greatly raised. When pathological pain is completely abolished, so is pinprick sensation. However, in a number of cases where pathological pain was only partially alleviated, pinprick sensation remained intact. The significance of these and other cases reported in the literature is discussed. The importance of clinically distinguishing between pain caused by tissue damage and pinprick sensation is emphasized, as well as that between return of pre-existing or new tissue-damage pain and painful dysesthesia.

Growth/differentiation factor-5 (GDF-5) and skeletal development.

BACKGROUND: Growth/differentiation factor-5 (GDF-5) has been shown to be essential for normal appendicular skeletal and joint development in humans and mice. In brachypod, a Gdf-5 gene mouse mutant, the defect is first apparent during early chondrogenesis, with the cartilage blastema already reduced in size by E12.5. This defect is associated with changes in the expression of cell surface molecules. METHODS: To understand further how GDF-5 controls cartilage formation, we first mapped the expression of the Gdf-5 gene during skeletal development (please note that the abbreviation for the gene is given in italics and the abbreviation for the protein expressed by the gene is given in capital letters). Subsequently, we over-expressed GDF-5 in the developing chick embryo using a replication competent retrovirus, RCAS(BP). We determined its effects on skeletal development by histological examination and its effects on early growth by autoradiography of proliferating cells. In addition, we examined the effect of GDF-5 on chondrogenic differentiation using micromass and single cell suspension cultures of limb mesenchymal cells, RESULTS: These studies show that the Gdf-5 gene is expressed in the early cartilage condensation, the perichondrium, and the joint interzone. Over-expresSion of GDF-5 in chick limb buds, during the condensation stage or later when the skeletal elements have formed, increased the size of the affected elements. In both cases, the increase in size was associated with an increase in cell number and, at later stages, this was correlated with an increase in S-phase cells. In vitro studies showed that GDF-5 could increase cell adhesiveness, and this may be a mechanism through which GDF-5 initiates condensation formation. CONCLUSION: These studies show that GDF-5 acts at two stages of skeletal development and by two distinct mechanisms. First, GDF-5 promotes the initial stages of chondrogenesis by promoting cell adhesion, which is consistent with the expression of Gdf-5 in the cartilage condensation. Second, GDF-5 can increase the size of the skeletal elements by increasing proliferation within the epiphyseal cartilage adjacent to its expression within the joint interzone.

Short communication: the use of sodium ironedetate (Sytron) as an MRI rectal contrast agent.

The use of bowel contrast medium in abdominal and pelvic MRI examinations is increasingly being recognized as a useful adjunct. A contrast agent which produces a negative contrast effect with T2 weighted (T2W) sequences might help distinguish bowel pathology, which has increased signal intensity, from bowel content. A solution of 7.6 mg ml-1 of sodium ironedetate (Sytron, Link Pharmaceuticals) produces positive contrast on the first (proton density) echo and negative contrast (signal void) on the second (T2W) echo of a dual echo sequence at 0.5 T. When administered rectally it provides a negative contrast bowel marker for pelvic examinations.

Teleradiology--practical aspects and lessons learnt.

Teleradiology is the most widely practised form of telemedicine and the necessary equipment is readily available. The limiting technical factor is often the communication links between the two sites. A balance must be struck between the degree of image compression and the transmission time. Non technical issues such as organisation of staff and medico-legal aspects must also be considered. Many problems can be avoided by written protocols and agreements.

Short test of semantic and phonological fluency: normal performance, validity and test-retest reliability.

Tests of verbal fluency, whether of Semantic Fluency (SF) or Phonological Fluency (PF), are often used as a standard method of neuropsychological assessment. However, very little normative data, standardized on a UK sample, is available, and little is known about the utility of popularly used 'short-forms' of these tasks. Additionally, very little is known about verbal fluency test-retest reliability. In this report we describe the performance of N = 365 normal participants on a version of SF requiring the generation of exemplars of the category 'animals' and a version of the PF task requiring participants to generate words beginning with the letter 'B'. From this data we have derived a percentile distribution for both tasks. We also addressed the impact of sex, age, years of education and IQ upon both SF and PF performance. No sex differences were found on either the PF or the SF tasks. A significant but small correlation between age and SF, but not PF, was observed. Modest correlations between both years of education and IQ and PF and SF performance were also seen. We also report test-retest reliability scores for performance on both SF and PF tasks. Performance on the longer 'FAS' version was found to correlate highly with scores obtained using just the letter 'B'. This suggests that little additional advantage obtains from administering three-letter versions of PF. An extremely high degree of correlation between SF tasks in which participants are given 1 minute and scores obtained when participants are given 1 minute 30 seconds was also observed. Finally, in order to assist users in deciding whether a changed retest score is due to error measurement or a real effect, we calculated Standard Error of Prediction (SEP) scores.

Characterisation and development of 'the shield' in male pigs.

A project was undertaken to characterise boar shield, study its development and determine whether it presents carcass quality problems in young boars used for meat production. In two old boars (>2·5 years) 'backfat' from the scapular region consisted mainly of a dense white tissue with a high collagen content (>20% of fresh weight) and a low lipid content (<10%) compared with normal backfat. Histologically and chemically it resembled the dermis of skin. In a development study in boars and castrates from the Large White and Pietrain breeds, collagen concentration in scapular backfat increased between 91 and 118 kg liveweight in all pigs but the increase was greater in boars than castrates and especially marked in Pietrain boars in which the mean collagen concentration was 18% at 118 kg. This was probably because of the older age of Pietrains since there was a high correlation between age and collagen concentration (r = 0·93). The results suggest that, at 'heavy hog' weights, boar shield could present a carcass quality problem in slow-growing breeds such as the Pietrain.

The first telemedicine link for the British Forces.

In January 1998 a telemedicine link was established between the Hospital Squadron (from 22 Field Hospital) in Sipovo, Bosnia and the Royal Hospital Haslar, United Kingdom (UK). This link uses a high resolution digital camera, laptop computer, satellite telephone and a landline to obtain specialist opinions in radiology, dermatology, plastic surgery, orthopaedics, urology, ophthalmology, pathology and maxillo-facial surgery. This is the Defence Medical Services' first such link from an operational scenario. As such, this pilot study provides a useful testbed to enable clinicians in the three services to gain experience in this developing field, and to help determine the military applications of telemedicine.

Operational telemedicine.

A simple, effective digital camera and E-mail-based telemedicine system has been developed using commercially available equipment. Initial trials were successful and this system is now deployed in several operational units. A retrospective audit has shown it to be of value in 50% of referrals.