Role of Kidney Stones in Renal Pelvis Flow.

Ureteroscopy is a commonly performed medical procedure to treat stones in the kidney and ureter using a ureteroscope. Throughout the procedure, saline is irrigated through the scope to aid visibility and wash-out debris from stone fragmentation. The key challenge that this research addresses is to build a fundamental understanding of the interaction between the kidney stones/stone fragments and the flow dynamics in the renal pelvis flow. We examine the time-dependent flow dynamics inside an idealized renal pelvis in the context of a surgical procedure for kidney stone removal. Here, we examine the time-dependent evolution of these vortical flow structures in three dimensions, and incorporate the presence of rigid kidney stones. We perform direct numerical simulations, solving the transient Navier-Stokes equations in a spherical domain. Our numerical predictions for the flow dynamics in the absence of stones are validated with available experimental and numerical data, and the governing parameters and flow regimes are chosen carefully in order to satisfy several clinical constraints. The results shed light on the crucial role of flow circulation in the renal cavity and its effect on the trajectories of rigid stones. We demonstrate that stones can either be washed out of the cavity along with the fluid, or be trapped in the cavity via their interaction with vortical flow structures. Additionally, we study the effect of multiple stones in the flow field within the cavity in terms of the kinetic energy, entrapped fluid volume, and the clearance rate of a passive tracer modeled via an advection-diffusion equation. We demonstrate that the flow in the presence of stones features a higher vorticity production within the cavity compared with the stone-free cases.

A temperature model for laser lithotripsy.

OBJECTIVE: To derive and validate a mathematical model to predict laser-induced temperature changes in a kidney during kidney stone treatment. METHODS: A simplified mathematical model to predict temperature change in the kidney for any given renal volume, irrigation flow rate, irrigation fluid temperature, and laser power was derived. We validated our model with matched in vitro experiments. RESULTS: Excellent agreement between the mathematical model predictions and laboratory data was obtained. CONCLUSION: The model obviates the need for repeated experimental validation. The model predicts scenarios where risk of renal tissue damage is high. With real-time knowledge of flow rate, irrigating fluid temperature and laser usage, safety warning levels could be predicted. Meanwhile, clinicians should be aware of the potential risk from thermal injury and take measures to reduce the risk, such as using room temperature irrigation fluid and judicious laser use.

The association of pre-operative home accelerometry with cardiopulmonary exercise variables.

We investigated the association of pre-operative activity, reported by the Duke Activity Score Index, Short Form-12 and measured by an accelerometer worn at home, with five cardiopulmonary exercise variables: peak power; peak oxygen consumption; anaerobic threshold; and ventilatory equivalents for oxygen and carbon dioxide. Fifty patients scheduled for major surgery underwent a standard pre-operative cardiopulmonary exercise test and wore a chest-mounted triaxial accelerometer for a mean (SD) duration of 3.2 (0.4) days. The Duke Activity Score Index and six accelerometer variables were significantly correlated with all five cardiopulmonary exercise variables, Pearson correlation coefficients 0.5-0.7, p = 0.02 to p < 0.001. Our results can guide future studies that measure physical activity for pre-operative assessment and interventions.

Label-free quantitative proteomics reveals differentially regulated proteins influencing urolithiasis.

Urinary proteins have been implicated as inhibitors of kidney stone formation (urolithiasis). As a proximal fluid, prefiltered by the kidneys, urine is an attractive biofluid for proteomic analysis in urologic conditions. However, it is necessary to correct for variations in urinary concentration. In our study, individual urine samples were normalized for this variation by using a total protein to creatinine ratio. Pooled urine samples were compared in two independent experiments. Differences between the urinary proteome of stone formers and nonstone-forming controls were characterized and quantified using label-free nano-ultraperformance liquid chromatography high/low collision energy switching analysis. There were 1063 proteins identified, of which 367 were unique to the stone former groups, 408 proteins were unique to the control pools, and 288 proteins were identified for comparative quantification. Proteins found to be unique in stone-formers were involved in carbohydrate metabolism pathways and associated with disease states. Thirty-four proteins demonstrated a consistent >twofold change between stone formers and controls. For ceruloplasmin, one of the proteins was shown to be more than twofold up-regulated in the stone-former pools, this observation was validated in individuals by enzyme-linked immunosorbent assay. Moreover, in vitro crystallization assays demonstrated ceruloplasmin had a dose-dependent increase on calcium oxalate crystal formation. Taken together, these results may suggest a functional role for ceruloplasmin in urolithiasis.

Detection of circulating tumour cells in peripheral blood with an automated scanning fluorescence microscope.

We have developed an automated, highly sensitive and specific method for identifying and enumerating circulating tumour cells (CTCs) in the blood. Blood samples from 10 prostate, 25 colorectal and 4 ovarian cancer patients were analysed. Eleven healthy donors and seven men with elevated serum prostate-specific antigen (PSA) levels but no evidence of malignancy served as controls. Spiking experiments with cancer cell lines were performed to estimate recovery yield. Isolation was performed either by density gradient centrifugation or by filtration, and the CTCs were labelled with monoclonal antibodies against cytokeratins 7/8 and either AUA1 (against EpCam) or anti-PSA. The slides were analysed with the Ikoniscope robotic fluorescence microscope imaging system. Spiking experiments showed that less than one epithelial cell per millilitre of blood could be detected, and that fluorescence in situ hybridisation (FISH) could identify chromosomal abnormalities in these cells. No positive cells were detected in the 11 healthy control samples. Circulating tumour cells were detected in 23 out of 25 colorectal, 10 out of 10 prostate and 4 out of 4 ovarian cancer patients. Five samples (three colorectal and two ovarian) were analysed by FISH for chromosomes 7 and 8 combined and all had significantly more than four dots per cell. We have demonstrated an Ikoniscope based relatively simple and rapid procedure for the clear-cut identification of CTCs. The method has considerable promise for screening, early detection of recurrence and evaluation of treatment response for a wide variety of carcinomas.

Evaluation of multidetector computed tomography urography and ultrasonography for diagnosing bladder cancer.

AIM: To evaluate and compare the diagnostic accuracy of multidetector computed tomography urography (CTU) and ultrasonography (US) for diagnosing bladder cancer. MATERIALS AND METHODS: A consecutive series of 143 patients over 40-years of age, presenting with macroscopic haematuria and without urinary tract infection underwent same-day CTU, US, and flexible cystoscopy. CTU and US were independently rated on a five-point scale for the presence of bladder cancer without knowledge of the reference standard of flexible or rigid cystoscopy and/or biopsy results. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analysis and likelihood ratios. RESULTS: For CTU, a rating of 5 (definitely tumour) was highly specific for bladder cancer (96.5%, 95%CI: 91.3-99%), effectively confirming diagnosis (positive likelihood ratio 25.6, 95%CI: 9.7-67.4). For US, specificity was also high (94.7%, 95%CI: 88.9-98%) with a positive likelihood ratio of 13.1 (95%CI: 5.8-29.6). Sensitivity at this rating was substantially higher for CTU (89.7%, 95%CI: 72.7-97.8%) than US (69%, 95%CI: 49.2-84.7%). Standardized partial area (Az) under the ROC curve between 95-100% specificity, representing the average sensitivity in this range, was significantly greater (0.88 versus 0.61, p<0.05) for CTU than US. CONCLUSION: The specificities of CTU and US for the diagnosis of bladder cancer were similar, but CTU was more sensitive. Although the sensitivity of CTU was not high enough to replace flexible cystoscopy in the diagnostic pathway, the high specificity enables direct referral to rigid cystoscopy, bypassing flexible cystoscopy and expediting diagnosis and treatment in those patients testing positive.

Shock-wave lithotripsy: variance within UK practice.

The objectives of this study are to determine the current treatment policies of UK shock-wave lithotripsy centres. Fixed-site lithotripter centres in the UK were identified via the national Therapeutic Interventions for Stones of the Ureter (TISU) study (n = 25). Questionnaires were completed regarding current SWL protocols for each centre, including management of anticoagulation, use of antibiotics and analgesia, urine testing, pacemakers, and arterial aneurysms. Data were collected regarding service delivery. Responses were obtained for 21 centres. Most centres use the Storz Modulith (85.7 %). Wide variation was observed in clinical contraindications to SWL, with 47.6 % centres performing SWL in patients with an abdominal aortic aneurysm, 66.7 % performing SWL in patients with a pacemaker, and 66.7 % of centres not performing SWL in asymptomatic patients with a urine dipstick positive for nitrites and leucocytes. The management of anticoagulation pre- and post-SWL showed wide variation, with the omission of anticoagulation ranging from 0 to 10 days pre-SWL. Seventeen distinct analgesia regimens were reported and prophylactic antibiotics are routinely administered in 25.0 % of centres. Tamsulosin is prescribed to all patients in 20.0 % of centres and a further 15.0 % of centres routinely prescribe tamsulosin post-SWL of ureteric stones. The included centres undertake SWL a median of 4 days per week and treat a median of six patients per list. Emergency SWL is unavailable in 30.0 % of centres. This observational real-life study has identified a significant disparity in the delivery of SWL throughout the UK, despite high numbers of patients with renal and ureteric stones being treated with this modality. Further studies should address the key areas of controversy, including an assessment of technical training, and facilitate the development of national guidelines to ensure a high level of standardized care for SWL patients.

Smartphone apps for urolithiasis.

There are an increasing number of healthcare smartphone applications ('apps') available. Urolithiasis presents a major healthcare burden. Patients are increasingly keen to educate themselves regarding the diagnosis and management of their condition. There is no formal regulation of healthcare apps, including a large number of apps relating to urolithiasis. This review aims to examine the range of apps available, and the prevalence of healthcare professional input. Four international smartphone app stores were searched: Apple's App Store, Google Play (Android), BlackBerry App World and the Windows Phone App store. A total of 42 unique apps were downloaded and analysed. Recorded data included the cost (£/$), publisher information, number of ratings, average rating and any documentation of medical professional involvement. Twenty-one (50%) apps required payment for download. The mean cost was £3.58 ($6.04) with range £0.61-£34.90 ($1.03-$58.87). Thirty-three (79%) of the 42 apps were designed to be used by patients. Fifteen (36%) of the 42 apps had clear input from health professionals. Twenty-two apps offered patient information, including dietary advice on lowering calcium intake, which is contrary to current evidence-based practice. We conclude that urolithiasis apps have future potential to inform both patients and healthcare professionals on stone management. However, inaccuracies in the recommendations made by some apps can be misleading or even harmful due to a lack of specialist involvement. We recommend improving the usefulness of these apps by seeking a 'quality stamp' from recognised urological organisations and greater clinician involvement in future app development.

Seasonal neuroendocrine rhythms in the male Siberian hamster persist after monosodium glutamate-induced lesions of the arcuate nucleus in the neonatal period.

The aim of these experiments was to examine the role of the arcuate nucleus in the control of seasonal cycles of body weight, feed intake, moulting and reproduction in the Siberian hamster. The arcuate nucleus has previously been implicated as a central site where systemic feedback signals (e.g. leptin) might act to regulate feed intake and body weight, so it was predicted that hamsters with lesions of this structure would be unable to display the inhibitory effects of short days on these parameters. In the first series of studies, lesions that destroyed approximately 80% of the cells in the arcuate nucleus were produced by treating hamsters neonatally with monosodium glutamate (MSG; 4 mg/g body weight sc), and vehicle- and MSG-treated males were raised from birth in long days (LD) or short days (SD). In hamsters raised in LD, the initial gain in body weight and testicular growth were significantly reduced by MSG treatment, however, growth rate and testis weight were still significantly greater than in vehicle- or MSG-treated hamsters raised in SD. In the second study, hamsters treated neonatally with vehicle or MSG were raised in LD for 8 weeks and, subsequently, approximately half in each group were transferred to SD for 18 weeks. As expected, vehicle-treated hamsters showed a characteristic decline in body weight when exposed to SD, while those remaining in LD continued to increase body weight. Feed intake decreased in parallel with the decline in body weight in SD, a complete moult to the white winter pelage occurred by 16 weeks in SD, and testicular regression occurred. Responses to SD also occurred in the MSG-treated hamsters: body weight decreased in SD but increased in their lesioned litter mates remaining in LD, and feed intake paralleled body weight changes in these groups. The moult to winter pelage was significantly retarded in MSG-treated hamsters transferred to SD. The testes were completely regressed in sham- and MSG-treated hamsters exposed to SD, whereas testes weights in MSG-treated hamsters maintained in LD were intermediate between those in vehicle-treated hamsters in SD and LD. Thus, despite initial effects on growth, the MSG-treated hamsters bearing substantial lesions of the arcuate nucleus were able to show appropriate responses to photoperiod, although not always of the same magnitude as the unlesioned controls. We conclude that feedback mechanisms operating via the arcuate nucleus are not the major regulators of seasonal cycles of body weight, feed intake, pelage and reproduction.

Obtaining patient feedback in an outpatient lithotripsy service is facilitated by use of a touch-screen tablet (iPad™) survey.

There is now a requirement for every doctor in the UK to obtain patient feedback for revalidation. This can be an onerous and time-consuming task. The objective of this study was to evaluate a novel electronic patient feedback method in an outpatient lithotripsy service setting. Between September 2013 and January 2014, 100 patients attending an outpatient lithotripsy service in Oxford were asked to complete a selection of pre-approved NHS questions about the service they had received. Questions were presented on a tablet device (iPad™) and answered using the touch screen. Departmental staff were unaware of the questions in the survey. Patients were asked to complete the survey by an independent research nurse. Questions were created online in a free-to-use web-based survey application and presented on the tablet device in a user-friendly format via an application. Data were uploaded via wifi™ to the online system. Data were viewed, automatically analysed and displayed graphically. The age range of the patients surveyed was 20-80 years of age. All 100 patients completed the survey without difficulty. All patients answered every question. Data could be automatically viewed, analysed and presented graphically. This method of collecting patient feedback proved to be rapid and efficient. The feedback highlighted a high patient satisfaction with the lithotripsy service. A touch screen tablet device is an efficient and effective method of collecting truly objective patient feedback. This method of patient feedback could be employed in other clinical environments to collect data for revalidation purposes.

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.

Amputations: no longer the end of the road.

BACKGROUND: The aim of this prospective study was to assess the effect of an intensive in-patient rehabilitation programme upon the mobility of amputees. METHODS: All major lower limb amputations between 1997 and 1999 received a pre-operative mobility assessment and, where appropriate, were referred for a vigorous rehabilitation programme. RESULTS: 92 lower limb amputations were performed in 87 patients (57 below knee, 33 above knee, two hip disarticulations). Overall, 63% of patients were able to ambulate independently following rehabilitation. Univariate analysis revealed that the only predictor of mobility was the level of amputation, below knee gaining better mobility than above knee (p=0.002). CONCLUSION: Lower limb amputees should participate in an aggressive in-patient physiotherapy regimen since reasonable mobility can be achieved in the majority of patients.

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.