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The Nuffield Department of Surgical Sciences is the academic department of surgery at the University of Oxford, and hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training.
Anatomy in a modern medical curriculum.
Anatomy in undergraduate education has been in decline for many years. Some suggest that it has fallen below a safe level. Balances between detail and safety, and assimilation and application of anatomy have yet to be established as the methods of teaching undergo another metamorphosis. For doctors, the human body is the focus of investigation and intervention on a daily basis; for this reason, the study of anatomy in some form will continue to be essential to safe medical practice. It is necessary for core knowledge of anatomy to be assimilated by all doctors in order to practice and communicate safely. It may be true that most doctors do not need to dissect a cadaver or study a prosection in order to practice, but if it can improve their understanding of what they do and why they do it, this surely has to be of benefit both for the safety of the patient and satisfaction of the doctor as a professional. Integration of newer teaching modalities and modern technology will encourage interest and retention of anatomical knowledge and its clinical relevance. Anatomy has a promising future in postgraduate specialist and surgical training. Detailed knowledge should be integrated into specialist training when it is clinically relevant allowing specialists of the future to practice safely and accurately and also to provide a strong base for future clinical developments.
The innervation of FGF-induced additional limbs in the chick embryo.
Motoneurones that supply the vertebrate limb innervate their muscle targets in a highly reproducible manner. As development proceeds, these limb-specific motoneurones send out axons, which grow towards the developing limb and then congregate at its base to form the plexus. In the plexus, in response to unknown positional cues, these axons rearrange, often changing their original spatial relationships, before sorting out to emerge in the defined nerve trunks that innervate the limb. Several proposals have been put forward to explain how this reproducible innervation pattern is achieved. These include (1) that early differences in the motoneurone identity dictate their future axonal trajectories, (2) that axons actively respond to attractive or repulsive positional cues provided by the limb bud itself, or (3) that motor axons are passively deployed, following pathways of least mechanical resistance. We have addressed the question of the relative roles of motoneurone identity and the signals that the axons encounter on their journey towards the limb bud. Using the developing chick embryo as our experimental model we tested the effect of providing an additional limb target for motor axons leaving the flank level of the spinal cord. To do this we placed FGF-soaked beads in the presumptive flank of 2-day-old chick embryos. This treatment induces an additional limb containing muscles. We investigated whether such additional limbs are innervated and by which neurones. We show that rather than the additional limbs being solely supplied by axons diverted from the two existing limb plexuses, motoneurones that normally supply the flank alter their trajectories to enter the induced limb. Once in the limb, axons respond to positional cues within the bud to generate the stereotypical innervation pattern. Our results show that the tendency of 'flank' motoneurones to innervate flank can be overcome by the presence of an additional limb.
Characterisation of vent designs in flexible and navigable suction ureteric access sheaths.
OBJECTIVES: To evaluate the different vent designs in three commercially available flexible and navigable suction (FANS) access sheaths-ClearPetra® (Well lead, Guangzhou, China), Elephant II (YIGAOMedical, Hangzhou, China) and Tuohy-Borst FANS access sheath (Seplou, Zhejiang, China)-and quantify the effects these differing designs have on the control of suction. METHODS: We conducted benchtop experiments to quantify the effect of pressure vent design on suction pressure control. Suction experiments were conducted both in an atmospheric beaker and in a phantom kidney model. With an indwelling 9.5-F LithoVue™ (Boston Scientific, Marlborough, MA, USA) ureteroscope, constant suction was applied to the access sheath's suction port. The vents were incrementally closed and corresponding flow rates calculated as a proxy for suction pressure. A mathematical model was developed to predict the impact of pressure control vent design on suction pressure control, flow rates and intrarenal pressure. RESULTS: For both the ClearPetra and Elephant II suction access sheaths, opening the length of the vent has an exponential reduction in suction pressure. Negligible suction is exerted on the renal pelvis with ≥3 mm of vent open. The Seplou suction access sheath has a Tuohy-Borst pressure vent, which allows finer control of suction pressures. The mathematical model showed strong agreement with experimental data. CONCLUSION: Commercially available FANS access sheaths are similar in most aspects but have differing vent designs. With the vents open no suction is exerted on the renal collecting system. However, because the flexible access sheath intrarenal end is within the renal pelvis, outflow resistance is low and the pelvis will deflate, giving the impression of suction. We have developed a mathematical model that predicts flow at different suction pressures and with different degrees of the pressure vents open. This allows simulations across multidimensional parameter spaces and the resulting quantitative predictions can be exploited to assess the implications of FANS access sheath and ureteroscope design.
Use of the probability of stone formation (PSF) score to assess stone forming risk and treatment response in a cohort of Brazilian stone formers.
INTRODUCTION: The aim was to confirm that PSF (probability of stone formation) changed appropriately following medical therapy on recurrent stone formers. MATERIALS AND METHODS: Data were collected on 26 Brazilian stone-formers. A baseline 24-hour urine collection was performed prior to treatment. Details of the medical treatment initiated for stone-disease were recorded. A PSF calculation was performed on the 24 hour urine sample using the 7 urinary parameters required: voided volume, oxalate, calcium, urate, pH, citrate and magnesium. A repeat 24-hour urine sample was performed for PSF calculation after treatment. Comparison was made between the PSF scores before and during treatment. RESULTS: At baseline, 20 of the 26 patients (77%) had a high PSF score (> 0.5). Of the 26 patients, 17 (65%) showed an overall reduction in their PSF profiles with a medical treatment regimen. Eleven patients (42%) changed from a high risk (PSF > 0.5) to a low risk (PSF < 0.5) and 6 patients reduced their risk score but did not change risk category. Six (23%) patients remained in a high risk category (> 0.5) during both assessments. CONCLUSIONS: The PSF score reduced following medical treatment in the majority of patients in this cohort.
The Fluid Mechanics of Ureteroscope Irrigation.
PURPOSE: To develop a physical understanding of ureterorenoscopy irrigation, we derive mathematical models from basic physical principles and compare these predictions with the results of benchtop experiments. Mathematical modeling can be used to understand the role of inlet pressure, tip deflection, the presence of working tools, geometric properties of the instruments used, and material properties of the irrigation fluid on resulting flow rate. MATERIALS AND METHODS: We develop theoretical models to describe irrigation flow in an idealized setup and compare with benchtop experiments for flow through a straight scope, a scope with a deflected tip, and a scope with a working tool inserted. The benchtop experiments were performed using Boston Scientific LithoVue ureteroscope and a variety of Boston Scientific working tools. Standard ureteroscope working channels have circular cross sections, but using theoretical models we investigate whether modifications to the cross-sectional geometry can enhance flow rates. RESULTS: The theoretical flow predictions are confirmed by experimental results. Tip deflection is shown to have a negligible effect on flow rate, but the presence of working tools decreases flow significantly (for a fixed driving pressure). Flow rate is predicted to improve when tools are placed at the edge of the channel, rather than the center, and modifying the cross-sectional shape from a circle to an ellipse can further increase flow rate. CONCLUSIONS: A mathematical framework is formulated and shown to accurately predict the properties of ureteroscope irrigation flow. The theoretical approach has significant potential in quantifying irrigation flow and improving ureteroscope design.
Fluid Intake and Dietary Factors and the Risk of Incident Kidney Stones in UK Biobank: A Population-based Prospective Cohort Study.
BACKGROUND: Fluid intake and diet are thought to influence kidney stone risk. However, prospective studies have been limited to small samples sizes and/or restricted measures. OBJECTIVE: To investigate whether fluid intake and dietary factors are associated with the risk of developing a first kidney stone. DESIGN, SETTING, AND PARTICIPANTS: Participants were selected from UK Biobank, a population-based prospective cohort study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazards models were used to investigate the association between fluid intake and dietary factors and the risk of a first incident kidney stone, ascertained from hospital inpatient records. RESULTS AND LIMITATIONS: After exclusion, 439 072 participants were available for the analysis, of whom 2057 had hospital admission with an incident kidney stone over a mean of 6.1 yr of follow-up. For every additional drink (200 ml) consumed per day of total fluid, the risk of kidney stones declined by 13% (hazard ratio [HR] = 0.87, 95% confidence interval [CI] 0.85-0.89). Similar patterns of associations were observed for tea, coffee, and alcohol, although no association was observed for water intake. Fruit and fibre intake was also associated with a lower risk (HR per 100 g increase of fruits per day = 0.88, 95% CI 0.83-0.93, and HR per 10 g fibre per day = 0.82, 95% CI 0.77-0.87), whereas meat and salt intake was associated with a higher risk (HR per 50 g increase in meat per week = 1.17, 95% CI 1.05-1.29, and HR for always vs never/rarely added salt to food = 1.33, 95% CI 1.12-1.58). Vegetable, fish, and cheese intake was not associated with kidney stone risk. CONCLUSIONS: The finding that high intake of total fluid, fruit, and fibre was associated with a lower risk of hospitalisation for a first kidney stone suggests that modifiable dietary factors could be targeted to prevent kidney stone development. PATIENT SUMMARY: We found that higher intake of total fluid, specifically tea, coffee, and alcohol (but not water), and consumption of fruit and foods high in fibre are linked with a reduced likelihood of developing kidney stones.
Impact of Case Volume on Shock Wave Lithotripsy Outcomes: Data from the National Shock Wave Lithotripsy Database of New Zealand.
Purpose: To assess the impact of individual operator case volume on shock wave lithotripsy (SWL) treatment outcomes in more than 9000 stone cases over a 20-year period in New Zealand. Materials and Methods: Stone cases treated with SWL on the Mobile Medical Technology (MMT) vehicle between June 19, 1995, and December 1, 2014, were identified. Data collection was undertaken prospectively for patient, stone, and treatment characteristics, and retrospectively for treatment outcomes. Multivariate analysis using binary logistic regression was undertaken to assess whether radiographer stone case volume (stones/year) was an independent predictor of SWL success (stone free or clinically insignificant residual fragments ≤4 mm at follow-up). Results: Sixteen radiographers delivered treatment to the included cohort (9039 stone cases), with a median case volume (stones/year) of 73 (range: 37-197) and median total of 425 stones treated (range: 71-1721). The two radiographers with highest case volumes achieved the highest success rates. Radiographer case volume (stones/year) was independently associated with SWL success (odds ratio [OR]: 1.004, 95% confidence interval [CI]: 1.003-1.005, p 150 cases per year.
Efficacy of the lithotripsy in treating lower pole renal stones.
Use of extracorporeal lithotripsy is declining in North America and many European countries despite international guidelines advocating it as a first-line therapy. Traditionally, lithotripsy is thought to have poor efficacy at treating lower pole renal stones. We evaluated the success rates of lithotripsy for lower pole renal stones in our unit. 50 patients with lower pole kidney stones ≤15 mm treated between 3/5/11 and 19/4/12 were included in the study. Patients received lithotripsy on a fixed-site Storz Modulith SLX F2 lithotripter according to a standard protocol. Clinical success was defined as stone-free status or asymptomatic clinically insignificant residual fragments (CIRFs) ≤3 mm at radiological follow-up. The mean stone size was 7.8 mm. The majority of stones (66 %) were between 5 and 10 mm. 28 % of stones were between 10 and 15 mm. For solitary lower pole stones complete stone clearance was achieved in 63 %. Total stone clearance including those with CIRFs was achieved in 81 % of patients. As expected, for those with multiple lower pole stones the success rates were lower: complete clearance was observed in 39 % and combined clearance including those with CIRFs was 56 %. Overall, complete stone clearance was observed in 54 % of patients and clearance with CIRFs was achieved in 72 % of patients. Success rate could not be attributed to age, stone size or gender. Our outcome data for the treatment of lower pole renal stones (≤15 mm) compare favourably with the literature. With this level of stone clearance, a non-invasive, outpatient-based treatment like lithotripsy should remain the first-line treatment option for lower pole stones. Ureteroscopy must prove that it is significantly better either in terms of clinical outcome or patient satisfaction to justify replacing lithotripsy.
The Essential Guide to Becoming a Doctor
Up-to-date, essential information for a wide group of school leavers Covers getting to medical school, being there and life thereafter Written by newly qualified doctors who lecture on medical careers This guide to applying successfully to ...
Essential Guide to Becoming a Doctor
All you need to know about becoming a doctor in the UK This book contains all the help you need to become a doctor.
Diagnostic Ureteroscopy
Ureteroscopy (URS) plays an important role in the diagnostic pathway for visible and persistent nonvisible hematuria from the upper urinary tract after initial radiological assessment. If a tumor of the upper urinary tract is suspected, URS is the most valid diagnostic step and allows for histology sampling. Other indications for diagnostic URS are suspected ureteric stricture and hydronephrosis of unknown origin. The diagnostic value is higher in the absence of a ureteric stent. Digital scopes may offer superior imaging quality in comparison to fibre optics. Every diagnostic URS includes a thorough cystoscopy. Manipulation in the ureter and collecting system should be as atraumatic as possible. After intubation of the ureteric orifice, a retrograde ureteropyelogram is performed. The ureter up to the pelviureteric junction is inspected with a semirigid ureteroscope; a flexible scope is used to inspect the collecting system. Urine cytologies should be obtained at different levels. Biopsies of suspicious lesions can be obtained with forceps or – for exophytic tumors – with stone baskets. Tumor grading is reliable but the local stage is often underestimated. In select cases, tumors of the upper tract may be treated endoscopically using holmium:YAG laser. A number of optical and fluorescence techniques have been introduced to enhance the diagnostic accuracy of URS but further studies are required to objectify their reliability.
Tracking kidney stones in a homogeneous medium using a trilateration approach.
Shock wave lithotripsy is a non-invasive procedure by which kidney stones are fragmented by thousands of shock waves. Currently, many shock waves are delivered to the body that do not impact the stone, but do result in tissue trauma. This motivates developing a monitoring system to locate kidney stones, with the goal of gating shock waves not aligned with the stone, and hence, reducing renal trauma during lithotripsy. The system consists of a circular array housing twenty-two 0.5 MHz transducers that can be mounted on a clinical lithotripter. It was deployed in a water tank and tested with two stone models made from gypsum cement and a stone model fragment. An algorithm consisting of threshold detection, automatic rejection of weak signals, and triangulation was developed to determine the location of stones. The results show that within ±15 mm of the focus of the lithotripter, the accuracy was better than 4 mm in the lateral directions and 2 mm in the axial direction. Using off-the-shelf hardware, the algorithm can calculate stone positions every 1 s allowing for real-time tracking during lithotripsy.
Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks
Background and purpose: IGF-1R depletion sensitizes prostate cancer cells to ionizing radiation and DNA-damaging cytotoxic drugs. This study investigated the hypothesis that IGF-1R regulates DNA double strand break (DSB) repair. Methods: We tested effects of IGF-1R siRNA transfection on the repair of radiation-induced DSBs by immunoblotting and immunofluorescence for γH2AX, and pulsed-field gel electrophoresis. Homologous recombination (HR) was quantified by reporter assays, and cell cycle distribution by flow cytometry. Results: We confirmed that IGF-1R depletion sensitized DU145 and PC3 prostate cancer cells to ionizing radiation. DU145 control transfectants resolved radiation-induced DSBs within 24 h, while IGF-1R depleted cells contained 30-40% unrepaired breaks at 24 h. IGF-1R depletion induced significant reduction in DSB repair by HR, although the magnitude of the repair defect suggests additional contributory factors. Radiation-induced G2-M arrest was attenuated by IGF-1R depletion, potentially suppressing cell cycle-dependent processes required for HR. In contrast, IGF-1R depletion induced only minor radiosensitization in LNCaP cells, and did not influence repair. Cell cycle profiles were similar to DU145, so were unlikely to account for differences in repair responses. Conclusions: These data indicate a role for IGF-1R in DSB repair, at least in part via HR, and support use of IGF-1R inhibitors with DNA damaging cancer treatments. © 2012 Elsevier Ireland Ltd. All rights reserved.
Fluid mechanical modeling of the upper urinary tract.
The upper urinary tract (UUT) consists of kidneys and ureters, and is an integral part of the human urogenital system. Yet malfunctioning and complications of the UUT can happen at all stages of life, attributed to reasons such as congenital anomalies, urinary tract infections, urolithiasis and urothelial cancers, all of which require urological interventions and significantly compromise patients' quality of life. Therefore, many models have been developed to address the relevant scientific and clinical challenges of the UUT. Of all approaches, fluid mechanical modeling serves a pivotal role and various methods have been employed to develop physiologically meaningful models. In this article, we provide an overview on the historical evolution of fluid mechanical models of UUT that utilize theoretical, computational, and experimental approaches. Descriptions of the physiological functionality of each component are also given and the mechanical characterizations associated with the UUT are provided. As such, it is our aim to offer a brief summary of the current knowledge of the subject, and provide a comprehensive introduction for engineers, scientists, and clinicians who are interested in the field of fluid mechanical modeling of UUT. This article is categorized under: Cancer > Biomedical Engineering Infectious Diseases > Biomedical Engineering Reproductive System Diseases > Biomedical Engineering.
The utility of automated volume analysis of renal stones before and after shockwave lithotripsy treatment.
This study aimed to evaluate the additional utility of an automated method of estimating volume for stones being treated with shockwave lithotripsy (SWL) using computed tomography (CT) images compared to manual measurement. Utility was assessed as the ability to accurately measure stone burden before and after SWL treatment, and whether stone volume is a better predictor of SWL outcome than stone diameter. 72 patients treated with SWL for a renal stone with available CT scans before and after treatment were included. Stone axes measurement and volume estimation using ellipsoid equations were compared to volume estimation using software using CT textural analysis (CTTA) of stone images. There was strong correlation (r > 0.8) between manual and CTTA estimated stone volume. CTTA measured stone volume showed the highest predictive value (r2 = 0.217) for successful SWL outcome on binary logistic regression analysis. Three cases that were originally classified as 'stone-free with clinically insignificant residual fragments' based on manual axis measurements actually had a larger stone volume based on CTTA estimation than the smallest fragments remaining for cases with an outcome of 'not stone-free'. This study suggests objective measurement of total stone volume could improve estimation of stone burden before and after treatment. Current definitions of stone-free status based on manual measurements of residual fragment sizes are not accurate and may underestimate remaining stone burden after treatment. Future studies reporting on the efficacy of different stone treatments should consider using objective stone volume measurements based on CT image analysis as an outcome measure of stone-free state.
Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.
BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear. METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P 70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis. FINDINGS: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10-1.29, q-value = 0.033, PPH4 = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20-1.69, q-value = 0.055, PPH4 = 73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR: 0.66, 95% CI: 0.53-0.81, q-value = 0.067, PPH4 = 81.8%), and interleukin-1 receptor-like 1 concentrations with decreased triple-negative breast cancer risk (OR: 0.92, 95% CI: 0.88-0.97, q-value = 0.15, PPH4 = 85.6%). These findings were replicated in pooled analyses with the FinnGen study. Though suggestive evidence was found to support an association of macrophage migration inhibitory factor concentrations with increased bladder cancer risk (OR: 2.46, 95% CI: 1.48-4.10, q-value = 0.072, PPH4 = 76.1%), this finding was not replicated when pooled with the FinnGen study. For 22 of 30 cancer outcomes examined, there was little evidence (q-value ≥0.20) that any of the 66 circulating inflammatory markers examined were associated with cancer risk. INTERPRETATION: Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 4 circulating inflammatory markers in risk of 4 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated. FUNDING: Cancer Research UK (C68933/A28534, C18281/A29019, PPRCPJT∖100005), World Cancer Research Fund (IIG_FULL_2020_022), National Institute for Health Research (NIHR202411, BRC-1215-20011), Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4), Academy of Finland Project 326291, European Union's Horizon 2020 grant agreement no. 848158 (EarlyCause), French National Cancer Institute (INCa SHSESP20, 2020-076), Versus Arthritis (21173, 21754, 21755), National Institutes of Health (U19 CA203654), National Cancer Institute (U19CA203654).