Centralised 3D printing in the NHS: a radiological review.

In recent years, three-dimensional (3D) printing has seen an explosion of interest fuelled by improvements in technology and associated reduction in costs. The literature is replete with novel medical applications of custom anatomical models, prostheses, and surgical guides. Although the fundamental core of 3D printing lies in image manipulation, the driving force in many National Health Service (NHS) trusts has come from individual surgical specialties with 3D printers independently run and confined to respective departments. In this review of 3D printing, experience of establishing a new centralised 3D-printing service within an NHS hospital trust is reported, focusing on the requirements and challenges of such an endeavour.

Engineering pyruvate decarboxylase-mediated ethanol production in the thermophilic host Geobacillus thermoglucosidasius.

This study reports the expression, purification, and kinetic characterization of a pyruvate decarboxylase (PDC) from Gluconobacter oxydans. Kinetic analyses showed the enzyme to have high affinity for pyruvate (120 µM at pH 5), high catalytic efficiency (4.75 × 10(5) M(-1) s(-1) at pH 5), a pHopt of approximately 4.5 and an in vitro temperature optimum at approximately 55 °C. Due to in vitro thermostablity (approximately 40 % enzyme activity retained after 30 min at 65 °C), this PDC was considered to be a suitable candidate for heterologous expression in the thermophile Geobacillus thermoglucosidasius for ethanol production. Initial studies using a variety of methods failed to detect activity at any growth temperature (45-55 °C). However, the application of codon harmonization (i.e., mimicry of the heterogeneous host's transcription and translational rhythm) yielded a protein that was fully functional in the thermophilic strain at 45 °C (as determined by enzyme activity, Western blot, mRNA detection, and ethanol productivity). Here, we describe the first successful expression of PDC in a true thermophile. Yields as high as 0.35 ± 0.04 g/g ethanol per gram of glucose consumed were detected, highly competitive to those reported in ethanologenic thermophilic mutants. Although activities could not be detected at temperatures approaching the growth optimum for the strain, this study highlights the possibility that previously unsuccessful expression of pdcs in Geobacillus spp. may be the result of ineffective transcription/translation coupling.

Metabolic engineering of Geobacillus thermoglucosidasius for high yield ethanol production.

We describe the metabolic engineering of two strains of Geobacillus thermoglucosidasius to divert their fermentative carbon flux from a mixed acid pathway, to one in which ethanol becomes the major product. This involved elimination of the lactate dehydrogenase and pyruvate formate lyase pathways by disruption of the ldh and pflB genes, respectively, together with upregulation of expression of pyruvate dehydrogenase. Unlike the situation in Escherichia coli, pyruvate dehydrogenase is active under anaerobic conditions in thermophilic bacilli, but expressed sub-optimally for a role as the primary fermentation pathway. Mutants were initially characterised in batch culture using glucose as carbon substrate and strains with all three modifications shown to form ethanol efficiently and rapidly at temperatures in excess of 60 degrees C in yields in excess of 90% of theoretical. The strain containing the 3 modifications, TM242, was also shown to efficiently ferment cellobiose and a mixed hexose and pentose feed.

Effects of prostaglandins E1 and E2 on human, guinea-pig and rat isolated small intestine.

1. Prostaglandins E(1) and E(2) contracted the longitudinal muscle of human, guinea-pig and rat isolated ileum.2. The site of action varied with the species. In the rat and in some strips of human tissue prostaglandin appeared to have only a direct action on or in the muscle cells. In the other strips of human tissue and in guinea-pig ileum the prostaglandins seemed to stimulate both the intrinsic cholinergic nerves and the muscle cells.3. In contrast to the longitudinal muscle, the circular muscle of human, guinea-pig and rat isolated ileum was usually inhibited by prostaglandin, apparently by an action directly on the muscle cells.4. Prostaglandins may play a part in the control of intestinal motility.

Effect of prostaglandins E1 and E2 on intestinal motility in the guinea-pig and rat.

1. Prostaglandins E(1) and E(2) affected intestinal activity both in vitro and in vivo.2. Serosal application of prostaglandin to guinea-pig isolated ileum stimulated the longitudinal muscle but reduced peristaltic contractions of the circular muscle and the propulsion of fluid through the gut. Intraluminal application had little effect.3. Injection of prostaglandin into the bloodstream of anaesthetized rats stimulated the longitudinal muscle of the ileum and increased the intraluminal pressure. A similar response sometimes occurred in the guinea-pig, but in general the effect was variable.4. Release of prostaglandin in the gut wall, but probably not into the blood or into the lumen of the gut, may play a part in controlling intestinal motility.

Inhibition of peristalsis in guinea-pig isolated ileum and colon by drugs that block prostaglandin synthesis.

1 Methods of analysing peristaltic activity have been evaluated by the use of recordings of longitudinal and circular muscle activity and of propulsion in whole segments of guinea-pig ileum and colon. 2 Some prostaglandin synthesis inhibitors, and antagonists of prostaglandin action were tested for their suitability for studying the role of prostaglandins in peristalsis. Aspirin was suitable; at 10-200 mug/ml it had little effect on responses of longitudinal muscle strips of the guinea-pig ileum to acetylcholine (ACh), histamine, nicotine or prostaglandin E2. Indomethacin (1-4 mug/ml) reduced responses to nicotine and prostaglandin E2. The prostaglandin antagonists polyphloretin phosphate and SC-19220 reduced contractions of ileal longitudinal muscle caused by nerve excitation with either nicotine or transmural stimulation. 3 Aspirin (20-100 mug/ml) or indomethacin (1-4 mug/ml) applied serosally greatly inhibited all aspects of peristalsis in guinea-pig ileum and colon. Inhibition of peristalsis of the ileum by aspirin was antagonized by prostaglandin E2 and that by indomethacin was removed by prostaglandin F2alpha or ACh. Inhibition of colonic peristalsis by aspirin was antagonized by prostaglandin E2 but rarely by ACh, and that by indomethacin by prostaglandin E1 or E2. Mucosal application of aspirin had little effect on either ileum or colon but indomethacin caused some inhibition. 4 These results support the supposition that prostaglandins contribute to peristaltic activity.

The effects of prostaglandins on guinea-pig isolated intestine and their possible contribution to muscle activity and tone.

1 Prostaglandins F(1alpha) and F(2alpha) caused contraction of the longitudinal muscle of both guinea-pig isolated ileum and colon, apparently by acting directly on the muscle and on cholinergic nerves. They had little effect on ileal circular muscle.2 Prostaglandins E(1) and E(2) caused contraction of the longitudinal muscle of guinea-pig isolated colon, apparently by acting directly on the muscle and on excitatory nerves which are non-cholinergic. Prostaglandin E(1) seems more effective than E(2) in stimulating these nerves.3 It seems likely that prostaglandin release in vitro maintains the tone of the longitudinal muscle of guinea-pig colon, whereas release of a prostaglandin E compound inhibits circular muscle tone.

Intestinal pH and propulsion: an explanation of diarrhoea in lactase deficiency and laxation by lactulose.

Subjects deficient in lactase may experience bloating, cramps and diarrhoea after ingesting milk, due to the unhydrolysed and poorly-absorbed lactose. The diarrhoea may result from an osmotic effect of the lactose itself or its poorly-absorbed acidic products of fermentation (Weijers, van de Kamer & others, 1961; Christopher & Bayless, 1971), possibly together with an alteration of sodium and water absorption due to the lowered colonic pH (Rousseau & Sladen, 1971). Laxation by lactulose (1-4-beta-galactosidofructose) may operate through an analogous mechanism. The drug is a synthetic dissaccharide which, in oral doses of 10-20 g, relieves chronic constipation (Wesselius-de Casparis, Braadbaart & others, 1968). It is neither hydrolysed by intestinal dissaccharidase (Dahlqvist & Gryboski, 1965) nor absorbed in the gut, but it is converted in the colon mainly to lactic and acetic acids by various bacteria including Lactobacillus acidophilus. Apart from the increased osmotic effect, the pH in the proximal colon falls markedly (Bown, Gibson & others, 1974), and larger doses may reduce stool pH. Weijers & others (1961) inferred that the acidic products formed from lactose in the colon stimulate propulsion, and K.S. Liem (Philips-Duphar) suggested to us that lactulose may relieve constipation partly by stimulation of propulsion due to the lowered pH. The experiments described below support this view.

The effects of prostaglandins E1, E2, F1alpha and F2alpha on guinea-pig ileal and colonic peristalis.

Prostaglandins (PGE1, E2, F1alpha and F2alpha) have been tested on the peristaltic reflex in isolated segments of guinea-pig ileum and colon using simultaneous recordings of fluid propulsion and longitudinal and circular muscle activity. Propulsion and circular muscle peristaltic activity were increased by serosally applied PGF compounds in the ileum and PGE or PGF compounds in the colon following initial contraction of the longitudinal muscle. This is consistent with a role for prostaglandins in peristalsis. Mucosally applied PGF compounds has no significant effect.

"Black Bone" MRI: a potential non-ionizing method for three-dimensional cephalometric analysis--a preliminary feasibility study.

OBJECTIVES: CT offers a three-dimensional solution to the inaccuracies associated with lateral cephalogram-based cephalometric analysis. However, it is associated with significant concerns regarding ionizing radiation exposure. MRI offers a non-ionizing alternative, but this has been less well investigated. We present a novel gradient echo MRI sequence ("Black Bone") and highlight the potential of this sequence in cephalometric analysis. METHODS: After regional ethics approval, "Black Bone" imaging was obtained in eight patients in whom lateral cephalograms were available. "Black Bone", T1 and T2 weighted spin echo imaging were obtained in the mid-sagittal plane, and measurements were compared with those obtained on the lateral cephalogram using both the Advantage Windows Workstation (GE Medical Systems, Buckinghamshire, UK) and the Dolphin(®) cephalometric software (v. 11.5.04.23, Premium; Dolphin Imaging, Chatsworth, CA) by one assessor. Further assessment was made by scoring the ease of landmark identification on a ten-point scale. RESULTS: "Black Bone" imaging surpassed T1 and T2 weighted imaging in terms of cephalometric landmark identification. A number of mid-sagittal cephalometric landmarks could not be clearly identified on T2 weighted imaging, making analysis impossible. Measurements on "Black Bone" demonstrated the smallest discrepancy when compared with those obtained on the lateral cephalogram. The discrepancy seen between measurements completed on mid-sagittal MRI and the lateral cephalogram was compounded by inherent inaccuracies of the lateral cephalogram. The overall mean discrepancy between distance measurements on "Black Bone" imaging and those on the lateral cephalogram was 1-2 mm. CONCLUSIONS: Overall, "Black Bone" MRI offered an improved method of cephalometric landmark identification over routine MRI sequences, and provides a potential non-ionizing alternative to CT for three-dimensional cephalometrics.

Automatic upstaging of tongue squamous cell carcinoma with lateral extrinsic muscle involvement is not justified.

The TNM classification for oral malignancies has been criticized for its upstaging to T4a when tumour involves styloglossus, hyoglossus, palatoglossus and genioglossus. The aims of this study were to (1) create an anatomical computer atlas of extrinsic tongue musculature, and (2) reassess the original staging of pre-treatment archived magnetic resonance images (MRI) of tongue carcinomas using the strict extrinsic muscle criteria. The anatomy of the extrinsic tongue muscles was mapped using images from the Visible Human Project (VHP) to create a computer model of the extrinsic tongue muscles. This was co-registered with 87 archived pre-staging MRI scans of tongue carcinomas to assess tumour ingress of the extrinsic tongue muscles. Of the 87 image sets reviewed, 16 were of superficial tumours not visible on MRI. In the remaining 71 cases that showed positive extrinsic muscle tumour ingress, 52% were upstaged from T1/2/3 tumours to cT4a based upon this finding. Extrinsic lateral and genioglossus muscle invasion did not predict occult cervical lymph node invasion or disease-related survival. In conclusion, tumour invasion of styloglossus or hyoglossus would result in the majority of lateral tongue tumours being staged T4a. Such stratification is of little clinical relevance, and an alternative more reliable method is required.

"Black bone" MRI: a potential alternative to CT when imaging the head and neck: report of eight clinical cases and review of the Oxford experience.

OBJECTIVE: The potential risks associated with ionising radiation are well documented. We have previously reported the "black bone" MRI sequence, useful when imaging cortical bone. The objective of this paper is to report our initial experience of this technique in patients undergoing imaging of the head and neck region. METHODS: Using the departmental database those patients having had "black bone" sequences of the head and neck performed as part of their MRI examination in the preceding 5 years were identified. The radiological reports were reviewed to identify those cases where "black bone" or conventional MRI sequences had been performed in place of the requested CT, and the patient medical records for these cases were reviewed. Medical record review was also conducted for those cases where it was considered that the pathological condition requiring imaging would ordinarily be investigated with CT. RESULTS: The "black bone" sequence had been performed in 69 patients as part of routine MRI of the head and neck. Of these, 67% (n=46) were performed in combination with CT imaging, the majority of cases being primary tumours. In four cases, an MRI was performed in place of the requested CT scan. We present eight clinical cases illustrating the potential benefits of the "black bone" sequence. CONCLUSIONS: "Black bone" MRI offers a radiation-free method of imaging the head and neck, and has been successfully utilised in a range of benign and malignant conditions affecting this region. Advances in knowledge Adoption of this approach, where feasible, would be a significant advance in radiation protection.

"Black bone" MRI: a partial flip angle technique for radiation reduction in craniofacial imaging.

The potential harmful effects of ionising radiation continue to be highlighted. Radiation reduction techniques have largely consisted of low-dose techniques rather than a shift to non-ionising methods of imaging. CT scanning is frequently employed for imaging the craniofacial skeleton despite being one of the key anatomical regions for radiation protection in view of the radiosensitive lens and thyroid gland. We describe a low flip angle gradient echo MRI sequence which provides high image contrast between bone and other tissues but reduces the contrast between individual soft tissues. This permits the "black bone" to be easily distinguished from the uniformity of the soft tissues. While maintaining a repetition time of 8.6 ms and an echo time of 4.2 ms, the flip angle which provided optimised suppression of both fat and water was identified to be 5°. The biometric accuracy of this sequence was confirmed using a phantom to obtain direct anatomical measurements and comparable CT scanning. The average discrepancy between black bone MRI measurements and direct anatomical measurements was 0.32 mm. Black bone MRI therefore has the potential to reduce radiation exposure by replacing CT scanning when imaging the facial skeleton, with particular scope for imaging benign conditions in the young.

Alveolar soft-part sarcoma of the tongue: report of a case and review of the literature.

Alveolar soft part sarcoma (ASPS) accounts for less than 1% of all sarcomas. More frequently encountered within the lower limbs, the authors present a 24-year-old male with ASPS presenting as an asymptomatic swelling of the lateral tongue. At 12 months post wide local excision of the lesion, the patient remains well with no evidence of local or regional recurrence. Histological and immunohistochemical features are diagnostic of ASPS. Whilst rare, head and neck surgeons should be aware of ASPS as a potential cause of slow growing lesions, as early surgical resection is vital in view of the propensity for metastatic spread.

A case of extensive ulcerating vasculitis following a BCG vaccination.

Adverse reactions following BCG vaccination are uncommon, with an estimated prevalance of 0.4 per 1000 vaccines [Lotte A, Wasz-Hockert O, Poisson N, et al. Second IUATLD study on complications induced by intradermal BCG vaccination. Bull Int Union Tuber 1988;63:47-59]. Complications include erythema, blistering, abscess formation, regional lymphadenitis and keloid formation. The onset of cutaneous tuberculosis (TB) has also been reported. We describe the case of 12-year-old girl who developed extensive primary ulceration involving most of her left upper arm at the site of a BCG vaccination. A skin graft to the arm failed to take at the periphery and the ulcerated area increased to involve most of the upper lateral arm. Over a period of 18 months, secondary lesions developed on her forehead prompting further investigation of a systemic disease process. Following extensive immunological and microbiological examination, a diagnosis of vaccine-induced granulomatous vasculitis was made and the patient responded to a combination of antituberculous therapy and steroids. Once the disease process was under control, skin grafting of the ulcerated area was successful in achieving wound closure. Non-healing ulceration may be referred to the plastic surgeon and a diagnosis of vasculitis should be considered in difficult cases. A multidisciplinary team approach involving immunologists, dermatologists and plastic surgeons provides the best opportunity for a successful long-term outcome in terms of disease control as well as immediate skin cover.

Modulation by prostaglandins of contractions in guinea-pig ileum.

A high concentration of indomethacin (40mu-g/ml) substantially reduced contractions of guinea-pig isolated ileum in Krebs solution to nerve stimulation with electrical pulses or nicotine. Responses to acetylcholine and histamine were also inhibited, but to a smaller extent. Low concentrations of prostaglandin E-2 (2 or 4ng/ml) mainly restored all the excitatory responses. Using a modified bathing solution (lacking in phosphate and with some other changes) indomethacin 0.36mu-g/ml selectively inhibited nerve-mediated contractions. The results explain differences in various reports, and support the possibility that prostaglandins modulate the response to cholinergic nerve activity.

A solvolytic C-C cleavage reaction of 6-acetoxycyclohexa-2,4-dienones: mechanistic implications for the intradiol catechol dioxygenases.

6-Acetoxycyclohexa-2,4-dienones are found to undergo a rapid reaction in methanol/water under mildly basic conditions to give an acyclic ketoester as the major product for 6-phenyl and 6-methyl substrates. Reaction monitoring by UV spectroscopy indicates the formation of an unsaturated ketone reaction intermediate (lambda(max) 275 nm, R = Ph) and the transient appearance of a highly conjugated species. Reaction of the 6-phenyl substrate (4.95 x 10(-6) s(-1)) is 2-fold faster than the 6-methyl substrate (2.47 x 10(-6) s(-1)). The reaction rate is first order with respect to substrate concentration, and the final step in the reaction is pH-dependent. No cleavage was observed for a substrate lacking an acetyl substituent. A reaction mechanism for C-C cleavage is proposed involving a benzene oxide-oxepin interconversion. The possible relevance to the catalytic mechanism of the intradiol catechol dioxygenases is discussed.