Search

Background: N-terminal pro-B type natriuretic peptide (NTpBNP) is a potential marker of cardiac failure. Methods: The Roche Elecsys™ 1010 and 2010 assays for NTpBNP were evaluated for precision, sample stability, and correlation between sample types and with other natriuretic peptides. Samples from 290 individuals aged 45–89 years with no cardiovascular risk factors, renal failure, electrocardiogram changes, evidence of structural abnormalities, or wall motion abnormalities on echocardiography and with an ejection fraction >50% were used to provide reference NTpBNP ranges. Results: The intra-assay imprecision was <10% across the analytical range and >3% at all concentrations analysed <30 ng/L. Inter-assay imprecision was 5.3–6.7% on the Elecsys 1010 and 4.4–5.0% on the Elecsys 2010, in the range 380–13000 ng/L. There was no statistically significant change in NTpBNP following storage in whole-blood samples at room temperature for 24 h before centrifugation; serum samples at room temperature for 7 days, at 4°C for up to 11 days on clot-activation gel or 22 days separated from the gel. NTpBNP concentrations were stable throughout five freeze–thaw cycles. There was a close correlation between NTpBNP concentrations in matched serum, EDTA plasma and lithium–heparin plasma samples. NTpBNP and BNP were more closely associated than were N-terminal proatrial natriuretic peptide and NTpBNP. This association was stronger at lower concentrations. NTpBNP concentrations increased with age, with values higher in women than men. Conclusions: NTpBNP is a stable molecule that can be measured easily and precisely using the Roche Elecsys 1010 or 2010 immunoassay analysers. [ABSTRACT FROM AUTHOR]

Purpose: Adrenal vein sampling (AVS) is used to lateralise and differentiate unilateral from bilateral aldosterone production in primary aldosteronism. The adrenal venous samples are standardised to a peripheral or low inferior vena cava (IVC) sample and compared. It is unknown whether the location of the non-adrenal sample affects the results. This study compares AVS results standardised to the low IVC and right external iliac vein (REIV)., Methods: Patients who underwent AVS between March 2021 and May 2023 were included. All procedures were undertaken by a single operator (AA). Demographic data and AVS results were collected from patients' electronic records. Catheterisation success and lateralisation were assessed using both low IVC and REIV samples. Equivalence test was used to compare the cortisol and aldosterone levels., Results: Eighty-one patients, (M: F = 38:43), aged between 29 and 74 were included. Bilateral successful adrenal vein cannulation was achieved in 79/81 (97.5%) cases. The mean cortisol levels from the REIV were statistically equivalent although there was a small and not biologically significant difference from the low IVC (respective geometric means 183 nmol/l vs. 185 nmol/l, p = 0.015). This small difference in cortisol may be due to accessory adrenal venous drainage into the IVC. The aldosterone and aldosterone/cortisol ratios were statistically equivalent. There was no discordance in selectivity or lateralisation when the IVC or REIV measurements were used., Conclusion: The IVC and REIV samples may be used interchangeably during AVS., (© 2024. The Author(s).)

Directional sensitivity, the more efficient response of cerebral autoregulation to increases, compared to decreases, in mean arterial pressure (MAP), has been demonstrated with repeated squat-stand maneuvers (SSM). In 43 healthy subjects (26 male, 23.1 ± 4.2 years old), five min. recordings of cerebral blood velocity (bilateral Doppler ultrasound), MAP (Finometer), end-tidal CO 2 (capnograph), and heart rate (ECG) were obtained during sitting (SIT), standing (STA) and SSM. A new analytical procedure, based on autoregressive-moving average models, allowed distinct estimates of the autoregulation index (ARI) by separating the MAP signal into its positive (MAP +D ) and negative (MAP -D ) derivatives. ARI +D was higher than ARI -D (p < 0.0001), SIT: 5.61 ± 1.58 vs 4.31 ± 2.16; STA: 5.70 ± 1.24 vs 4.63 ± 1.92; SSM: 4.70 ± 1.11 vs 3.31 ± 1.53, but the difference ARI +D -ARI -D was not influenced by the condition. A bootstrap procedure determined the critical number of subjects needed to identify a significant difference between ARI +D and ARI -D , corresponding to 24, 37 and 38 subjects, respectively, for SSM, STA and SIT. Further investigations are needed on the influences of sex, aging and other phenotypical characteristics on the phenomenon of directional sensitivity of dynamic autoregulation.

Treating open fractures in long bones can be challenging and if not performed properly can lead to poor outcomes such as mal/non-union, deformity, and amputation. One of the most common methods of treating these fracture types is temporary external fixation followed by definitive fixation. The shortage of high-quality affordable external fixators is a long-recognised need, particularly in Low- and Middle-Income Countries (LMICs). This research aimed to develop a low-cost device that can be manufactured locally to international standards. This can provide surge capacity for conflict zones or in response to unpredictable incidents and situations. The fixator presented here and developed by us, the Imperial external fixator, was tested on femur and tibia specimens under 100 cycles of 100 N compression-tension and the results were compared with those of the Stryker Hoffmann 3 frame. The Imperial device was stiffer than the Stryker Hoffmann 3 with a lower median interfragmentary motion (of 0.94 vs. 1.48 mm). The low-cost, easy to use, relatively lightweight, and easy to manufacture (since minimum skillset and basic workshop equipment and materials are needed) device can address a critical shortage and need in LMICs particularly in conflict-affected regions with unpredictable demand and supply. The device is currently being piloted in three countries for road traffic accidents, gunshot wounds and other conflict trauma-including blast cohorts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Saeidi, Barnes, Berthaume, Holthof, Milandri, Bull and Jeffers.)

Aging is associated with a number of alterations to cerebrovascular function. We aimed to investigate the effect of age on cerebrovascular responses to cognitive stimulation using an objective two-parameter method.Previously derived from a large data-set (135 healthy participants) were applied to a task-activated dataset of 69 healthy participants in five different task conditions. Cumulative response rate (CRR) was calculated as the sum of responses across tasks and hemispheres.There was a significant effect of age (adjusted odds ratio: 1.02 (95% confidence interval: 1.01, 1.04), p = 0.016). There was also a significant effect of task (p = 0.002), but there was no significant interaction between age and task (p = 0.37). Increasing age was associated with increased CRR (adjusted odds ratio: 1.04 (95% confidence interval: 1.01, 1.07), p = 0.009).Using an objective two-parameter method, healthy older adults had increased cerebrovascular responses to cognitive testing.

Parkinson's disease (PD) is a common neurodegenerative disorder, yet little is known about cerebral haemodynamics in this patient population. Previous studies assessing dynamic cerebral autoregulation (dCA), neurovascular coupling (NVC) and vasomotor reactivity (VMR) have yielded conflicting findings. By using multi-variate modelling, we aimed to determine whether cerebral blood flow (CBF) regulation is impaired in PD patients.55 healthy controls (HC) and 49 PD patients were recruited. PD subjects underwent a second recording following a period of abstinence from their anti-Parkinsonian medication. Continuous bilateral transcranial Doppler in the middle cerebral arteries, beat-to-beat mean arterial blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO 2 (EtCO 2 ; capnography) were measured. After a 5-min baseline period, a passive motor paradigm comprising 60 s of elbow flexion was performed. Multi-variate modelling quantified the contributions of MAP, ETCO 2 and neural stimulation to changes in CBF velocity (CBFV). dCA, VMR and NVC were quantified to assess the integrity of CBF regulation.Neural stimulation was the dominant input. dCA, NVC and VMR were all found to be impaired in the PD population relative to HC (p < 0.01, p = 0.04, p < 0.01, respectively). Our data suggest PD may be associated with depressed CBF regulation. This warrants further assessment using different neural stimuli.

Background: In people with acute ischaemic stroke, platelets become activated and can cause blood clots to form and block an artery in the brain, resulting in damage to part of the brain. Such damage gives rise to the symptoms of stroke. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and also reduce the risk of early recurrent ischaemic stroke, thereby reducing the risk of early death and improving long-term outcomes in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage., Objectives: To assess the efficacy and safety of immediate oral antiplatelet therapy (i.e. started as soon as possible and no later than two weeks after stroke onset) in people with acute presumed ischaemic stroke., Search Methods: We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, and two trials registers, and performed forward reference/cited reference searching in August 2020., Selection Criteria: Randomised controlled trials (RCTs) comparing oral antiplatelet therapy (started within 14 days of the stroke) with control in people with definite or presumed ischaemic stroke., Data Collection and Analysis: Two review authors independently applied the inclusion criteria and assessed trial quality. For the included trials, they extracted and cross-checked the data. They assessed risk of bias of each study using the Risk of Bias 1 (RoB1) tool and overall certainty of the evidence for each outcome using the GRADE approach., Main Results: We included 11 studies involving 42,226 participants. Three new trials have been added since the last update (743 participants). As per the previous version of this review, two trials testing aspirin 160 mg to 300 mg once daily, started within 48 hours of onset, contributed 96% of the data. The risk of bias was low. The maximum follow-up was six months. With treatment, there was a decrease in death or dependency at the end of follow-up (odds ratio (OR) 0.95, 95% confidence interval (CI) 0.91 to 0.99; 7 RCTs, 42,034 participants; moderate-certainty evidence). For every 1000 people treated with aspirin, 13 people would avoid death or dependency (number needed to treat for an additional beneficial outcome 79)., Authors' Conclusions: Antiplatelet therapy with aspirin 160 mg to 300 mg daily, given orally (or by nasogastric tube or per rectum in people who cannot swallow) and started within 48 hours of onset of presumed ischaemic stroke, significantly decreased death and dependency, and reduced the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications; long-term outcomes were improved., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Aldosterone and renin are pivotal hormones in the regulation of salt and water homeostasis and blood pressure. Measurement of renin and aldosterone in serum/plasma is essential for the investigation of primary hyperaldosteronism (PA) and monitoring of glucocorticoid replacement therapy., Methods: We report 2 LC-MS/MS methods developed to measure aldosterone and plasma renin activity (PRA). PRA was determined by endogenous enzymatic generation of angiotensin I using 150 µL of sample. Generated angiotensin I was purified by solid phase extraction prior to chromatographic separation and mass spectrometry. Aldosterone measurement required 300 μL of sample extracted with MTBE prior to LC-MS/MS analysis., Results: The PRA method was linear (1.2-193 nmol/L), sensitive (LLOQ = 1.2 nmol/L), precise (CV = 4.1%), and specific (no cross reactivity for a number of structurally similar steroids). Dilutional linearity and recovery (84%) were acceptable. Accuracy was confirmed by comparison against our current RIA method. The aldosterone method had equally acceptable performance characteristics. Reference ranges in 110 healthy normotensive subjects were: PRA 0.2-3.7 nmol/L/h and aldosterone 50-950 pmol/L. Consecutive patients (n = 62) with adrenal incidentalomas shown to have no functional adrenal disease; their post overnight 1 mg dexamethasone test values were: PRA 0.2-2.6 nmol/L/h and aldosterone 55-480 pmol/L. Serum aldosterone values after 2 liter saline suppression were-normal subjects (n = 17): 78-238 pmol/L and confirmed primary hyperaldosteronism (n = 25): 131-1080 pmol/L., Conclusions: We have developed robust assays for PRA and aldosterone with appropriate clinical evaluation. These assays are now in routine practice in the UK., (© Crown copyright 2020.)

Background: Neurovascular coupling (NVC) can be assessed using transcranial Doppler (TCD) measured task-activation of cerebral blood flow velocity (CBFv). However, not all individuals show consistent responses. The aim of this study was to develop a robust, objective, method to identify non-responders to task-activation., New Method: Using five-minute seated resting (non-stimulated), bilateral CBFv data from 135 healthy participants, the cross-correlation function peak (CCF) between the population coherent average and each individual was obtained for a randomly selected segment of data (40 s) for both hemispheres (n = 270). The variance ratio (VR) was calculated by comparing the variance in CBFv data pre- and post-random mark. The 90th percentile for non-stimulated data was used to determine the upper confidence limit of normal variation in the CCF peak value (0.53), and VR (2.59). These criteria were then applied to task-activated CBFv from 69 healthy participants for five cognitive tasks (attention, verbal fluency, language, visuospatial, memory)., Results: Data were accepted as responders if either CCF ≥ 0.53 or VR ≥ 2.59. The number of cases accepted as responders for each task were as follows: attention, 54-59 (78-86 %); verbal fluency, 42-48 (60-70 %); language, 51-53 (74-77 %); visuospatial, 54 (78 %); memory, 40-47 (58-68 %)., Comparison With Existing Method: Currently, there are no objective criteria for the identification of non-responders in studies of NVC. This is a new method to objectively classify non-responders to task-activation., Conclusions: Using a large sample of resting CBFv data, we have set objective criteria to differentiate between responders and non-responders in task activation protocols., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In comparison to through-knee amputees the outcomes for above-the-knee amputees are relatively poor; based on this novel techniques have been developed. Most current percutaneous implant-based solutions for transfemoral amputees make use of high stiffness intramedullary rods for skeletal fixation, which can have risks including infection, femoral fractures, and bone resorption due to stress shielding. This work details the cadaveric testing of a short, cortical bone stiffness-matched subcutaneous implant, produced using additive manufacture, to determine bone implant micromotion and push-out load. The results for the micromotions were all <20 μm and the mean push-out load was 2,099 Newtons. In comparison to a solid control, the stiffness-matched implant exhibited significantly higher micromotion distributions and no significant difference in terms of push-out load. These results suggest that, for the stiffness-matched implant at time zero, osseointegration would be facilitated and that the implant would be securely anchored. For these metrics, this provides justification for the use of a short-stem implant for transfemoral amputees in this subcutaneous application. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2104-2111, 2019., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Purpose: Squat-stand manoeuvres (SSMs) have been used to induce blood pressure (BP) changes for the reliable assessment of dynamic cerebral autoregulation. However, they are physically demanding and thus multiple manoeuvres can be challenging for older subjects. This study aimed to determine the minimum number of SSMs required to obtain satisfactory coherence, thus minimising the subjects' workload., Method: 20 subjects performed SSMs at a frequency of 0.05 Hz. End-tidal CO 2 , cerebral blood flow velocity, heart rate, continuous BP and the depth of the squat were measured. 11 subjects returned for a repeat visit. The time points at which subjects had performed 3, 6, 9, 12 and 15 SSMs were determined. Transfer function analysis was performed on files altered to the required length to obtain estimates of coherence and the autoregulation index (ARI)., Results: After three SSMs, coherence (0.05 Hz) was 0.93 ± 0.05, and peaked at 0.95 ± 0.02 after 12 manoeuvres. ARI decreased consecutively with more manoeuvres. ARI was comparable across the two visits (p = 0.92), but coherence was significantly enhanced during the second visit (p < 0.01). The intra-subject coefficients of variation (CoV) for ARI remained comparable as the number of manoeuvres varied., Conclusions: This analysis can aid those designing SSM protocols, especially where participants are unable to tolerate a standard 5-min protocol or when a shorter protocol is needed to accommodate additional tests. We emphasise that fewer manoeuvres should only be used in exceptional circumstances, and where possible a full set of manoeuvres should be performed. Furthermore, these results need replicating at 0.10 Hz to ensure their applicability to different protocols.

Dynamic cerebral autoregulation (CA), the transient response of cerebral blood flow (CBF) to rapid changes in arterial blood pressure (BP), is usually modeled as a linear mechanism. We tested the hypothesis that dynamic CA can display nonlinear behavior resulting from differential efficiency dependent on the direction of BP changes. Cerebral blood velocity (CBV) (transcranial Doppler), heart rate (HR) (three-lead ECG), continuous BP (Finometer), and end-tidal CO 2 (capnograph) were measured in 10 healthy young subjects during 15 squat-stand maneuvers (SSM) with a frequency of 0.05 Hz. The protocol was repeated with a median (interquartile range) of 44 (35-64) days apart. Dynamic CA was assessed with the autoregulation index (ARI) obtained from CBV step responses estimated with an autoregressive moving-average model. Mean BP, HR, and CBV were different (all P < 0.001) between squat and stand, regardless of visits. ARI showed a strong interaction ( P < 0.001) of SSM with the progression of transients; in general, the mean ARI was higher for the squat phase compared with standing. The changes in ARI were partially explained by concomitant changes in CBV ( P = 0.023) and pulse pressure ( P < 0.001), but there was no evidence that ARI differed between visits ( P = 0.277). These results demonstrate that dynamic CA is dependent on the direction of BP change, but further work is needed to confirm if this finding can be generalized to other physiological conditions and also to assess its dependency on age, sex and pathology.

Background: Patient home-based self-assessments after shoulder surgery have the potential to aid clinicians in reducing clinic time and decreasing follow-up requirements. The purpose of this systematic review was to determine the correlation between patient-based and physician-assessed outcome measures for range of motion (ROM), strength, and shoulder function., Methods: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. MEDLINE, Embase, CINAHL, and Cochrane Central Register of Controlled Trials databases were searched. All studies comparing patient-reported and clinician-based assessments of shoulder ROM, strength, and function were eligible for inclusion. Studies that included patient or clinician assessment only, description of shoulder diseases or treatments only, and animal- or cadaveric-based studies were excluded. More than 250 abstracts were searched, and 4 studies were found eligible., Results: Patients assessed their shoulder ROM, strength, and function with moderate-to-high accuracy compared with clinical assessment. There was less agreement between patients and clinicians regarding the symptomatic shoulder compared with the contralateral shoulder. There was less agreement between patients and clinicians on rotation than forward elevation. Patients who were less satisfied with their shoulder had less agreement with clinicians., Conclusion: There is moderate-to-high agreement between patients and clinicians in the assessment of the shoulder after surgery. Methods of assessment of rotation could be reviewed to create a more exact self-assessment tool., (Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Squat-stand maneuvers (SSMs) have been used to improve the coherence of transfer function analysis (TFA) estimates during the assessment of dynamic cerebral autoregulation (dCA). There is a need to understand the influence of peripheral changes resulting from SSMs on cerebral blood flow, which might confound estimates of dCA. Healthy subjects ( n = 29) underwent recordings at rest (5-min standing) and 15 SSMs (0.05 Hz). Heart rate (three-lead ECG), end-tidal CO 2 (capnography), blood pressure (Finometer), cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery), and the angle of the thigh (tilt sensor) were measured continuously. The response of CBV to SSMs was decomposed into the relative contributions of mean arterial pressure (MAP), resistance-area product (RAP), and critical closing pressure (CrCP). Upon squatting, a rise in MAP (83.6 ± 21.1% contribution) was followed by increased CBV. A dCA response could be detected, determined by adjustments in RAP and CrCP (left hemisphere) with peak contributions of 24.8 ± 12.7% and 27.4 ± 22.8%, respectively, at different times during SSMs. No interhemispheric differences were detected. During standing, the contributions of MAP, RAP, and CrCP changed considerably. In conclusion, the changes of CBV subcomponents during repeated SSMs indicate a complex response of CBV to SSMs that can only be partially explained by myogenic mechanisms. More work is needed to clarify the potential contribution of other cofactors, such as breath-to-breath changes in Pco 2 , heart rate, stroke volume, and the neurogenic component of dCA. NEW & NOTEWORTHY Here, we describe the different contributions to the cerebral blood flow response after squat-stand maneuvers. Furthermore, we demonstrate the complex interaction of peripheral and cerebral parameters for the first time. Moreover, we show that the cerebral blood velocity response to squatting is likely to include a significant metabolic component.

Squat/stand maneuvers (SSM) have been used to assess dynamic cerebral autoregulation (dCA), but always at a fixed frequency (FF). This study aimed to assess the use of random-frequency (RF) SSMs as a stimulus for measuring dCA and determine the reproducibility of FF and RFSSMs. Twenty-nine healthy volunteers [19 male, mean age 23.0 (4.9) yr] completed the study; 11 returned for a repeat visit (median 45 days). Heart rate, beat-to-beat blood pressure, middle cerebral artery (MCA) blood flow velocity, end-tidal CO 2 , and angle of the squat movement were measured. Subjects underwent four recordings: 5 min sitting, 5 min standing, FFSSMs (0.05Hz), and RFSSMs. Subjects were asked to rate the degree of exertion experienced while performing these maneuvers. Twenty-nine subjects completed the protocol; nine data sets were deemed unsuitable for further analysis. Mean ARI of 6.21 (1.04) while standing was significantly greater than during the SSMs ( P < 0.01), with mean (SD) ARI during the FF and RFSSMs being 5.16 (1.43) and 5.37 (1.21), respectively. However, no significant difference was found between the ARI estimates from the two SSMs ( P = 0.856) or for each of the four recordings between the two visits ( P = 0.645). RFSSMs were found to be significantly less tiring than FFSSMs ( P < 0.01). In conclusion, RFSSMs are an effective and noninvasive method of assessing dCA. There is no difference in the ARI estimates in comparison with FFSSMs. Although FFSSMs have been well tolerated previously, RFSSMs are preferred by healthy subjects and thus may be better tolerated by a patient population in a clinical setting. NEW & NOTEWORTHY RFSSMs provided comparable estimates of autoregulatory indices to FFSSMs. Instead of point estimates at the driven frequency, RFSSMs generate a broader power spectrum of changes in arterial blood pressure and cerebral blood flow velocity, allowing direct comparison with spontaneous fluctuations through transfer function analysis. Moreover, random-frequency SSMs are preferred by participants. They are a novel tool by which larger blood pressure oscillations can be elicited for the reliable measurement of dynamic cerebral autoregulation., (Copyright © 2017 the American Physiological Society.)

Background Using an online survey, we collected data to present a picture of how clinical authorization is performed in the UK. Methods A 21-question survey was uploaded to www.surveymonkey.com , and responses were invited via the mail base of the Association for Clinical Biochemistry and Laboratory Medicine. The questionnaire examined the intensity and function of the duty biochemist role and how different types of authorization are used to handle and release results. Results Of 70 responses received, 60 were suitable for analysis. Responses were received from every region of the UK. A typical duty biochemist shift started on average at 8:50, and finished at 17:25. The mean duration was 8 h 58 min. Clinical scientists are the most abundantly represented group on duty biochemist rotas. Higher banded clinical scientists and chemical pathologists covered out-of-hours shifts. Results were handled differently depending on the level of abnormality and the requesting area. Normal results tended to be released either directly from the analyser or after technical then autoauthorization (90%). A greater preference for clinical authorization was seen for abnormal and critical results originating from outpatients (49% and 69%, respectively) or general practice (51% and 71%) than for inpatients (33% and 53%) or A&E (25% and 37%). Conclusions The handling and authorization of biochemistry results varies greatly between laboratories. The role is clearly heterogeneous in the UK. Guidance from the Association for Clinical Biochemistry and Royal College of Pathologists may help to clarify the essential roles of the duty biochemist.

The urinary bladder is an organ which facilitates the storage and release of urine. The bladder can develop tumours and bladder cancer is a common malignancy throughout the world. There is a consensus that there are differences in the mechanical properties of normal and malignant tissues. However, the viscoelastic properties of human bladder tumours at the macro-scale have not been previously studied. This study investigated the viscoelastic properties of ten bladder tumours, which were tested using dynamic mechanical analysis at frequencies up to 30Hz. The storage modulus ranged between 0.052MPa and 0.085MPa while the loss modulus ranged between 0.019MPa and 0.043MPa. Both storage and loss moduli showed frequency dependent behaviour and the storage modulus was higher than the loss modulus for every frequency tested. Viscoelastic properties may be useful for the development of surgical trainers, surgical devices, computational models and diagnostic equipment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The aim of this work was to design an add-on instrument that could potentially decrease the recurrence of non-muscle invasive bladder cancer. The current surgical approach permits spilled tumour cells to disseminate within the bladder, re-implant and cause tumour recurrence. An add-on instrument has been designed in the form of an opening cone intended to provide space for surgery and yet reduce tumour cell spillage and dissemination. A prototype was manufactured using the shape memory metal Nitinol which was activated using an electrical current to facilitate opening and supplemented with latex to provide a sealed environment. The prototype was tested in comparable surgical conditions utilising porcine bladder wall and blue dye to simulate tumour cells. It was demonstrated that the vast majority of dye was retained within the device, supporting the proposed aim., (© IMechE 2016.)

The purpose of this study was to quantify the frequency dependent viscoelastic properties of two types of spinal posterior dynamic stabilisation devices. In air at 37°C, the viscoelastic properties of six BDyn 1 level, six BDyn 2 level posterior dynamic stabilisation devices (S14 Implants, Pessac, France) and its elastomeric components (polycarbonate urethane and silicone) were measured using Dynamic Mechanical Analysis. The viscoelastic properties were measured over the frequency range 0.01-30Hz. The BDyn devices and its components were viscoelastic throughout the frequency range tested. The mean storage stiffness and mean loss stiffness of the BDyn 1 level device, BDyn 2 level device, silicone component and polycarbonate urethane component all presented a logarithmic relationship with respect to frequency. The storage stiffness of the BDyn 1 level device ranged from 95.56N/mm to 119.29N/mm, while the BDyn 2 level storage stiffness ranged from 39.41N/mm to 42.82N/mm. BDyn 1 level device and BDyn 2 level device loss stiffness ranged from 10.72N/mm to 23.42N/mm and 4.26N/mm to 9.57N/mm, respectively. No resonant frequencies were recorded for the devices or its components. The elastic property of BDyn 1 level device is influenced by the PCU and silicone components, in the physiological frequency range. The viscoelastic properties calculated in this study may be compared to spinal devices and spinal structures., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The aim of this study was to measure the viscoelastic properties of bladder tissue. Porcine bladders were dissected into rectangular strips and loops. Dynamic Mechanical Analysis was used to measure the viscoelastic properties of the bladder tissue (storage and loss stiffness) tested in a frequency range of up to 10 Hz. Storage stiffness was found to be consistently higher than loss stiffness. Average storage stiffness was found to be 1.89 N/mm and 0.74 N/mm for looped and rectangular samples, respectively. Average loss stiffness was found to be 0.24 N/mm and 0.11 N/mm for looped and rectangular samples, respectively. The results of this study are important for computational modelling of the bladder and for ensuring that engineered bladder tissues have physiological viscoelastic properties., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This chapter describes the measurement of plasma renin activity by calculation of the quantity of angiotensin I that is released in plasma by the action of endogenous enzyme renin on angiotensinogen, the endogenous substrate. Details are given for the generation of angiotensin I from plasma using controlled pH and temperature conditions. The generated angiotensin I is then quantified by a radioimmunoassay using anti-angiotensin I antibody and iodinated angiotensin I as label. Separation of the antibody-bound fraction from the unbound is achieved using dextran-coated charcoal. Additional notes describe critical steps in the assay. The correct procedures for sample handling to overcome the potential problems of cryoactivation of prorenin to renin are described.

This chapter describes the measurement of aldosterone concentration in plasma or serum. Aldosterone specificity is improved by first extracting the aldosterone into dichloromethane. A radioimmunoassay is then performed on the dried and reconstituted extract using an anti-aldosterone antibody and iodinated aldosterone. The antibody-bound fraction is separated from the unbound fraction using activated charcoal. The notes section provides extra information for steps in the assay that can be problematic.

Background: Primary hyperaldosteronism (PHA) is characterized by a raised plasma aldosterone concentration (PAC) with suppressed plasma renin activity (PRA). We evaluated two renin mass methods for PHA detection compared with the PAC:PRA ratio., Methods: Samples from patients attending a specialist hypertensive clinic were analysed by Liaison automated chemiluminescent immunoassay and Diagnostic Systems Laboratories (DSL) immunoradiometric assay (IRMA) for renin mass; I(-125) radioimmunoassay of angiotensin I generated from endogenous angiotensinogen for PRA; Siemens Coat-a-count radioimmunoassay for PAC. Subjects included those on β-blockers which suppress renin, causing an equivalent biochemical picture to PHA. Aldosterone/renin ratios (ARR) were calculated for PRA, DSL and Liaison methods. The first 100 subjects were used to identify cut-off ratios ensuring maximum specificity at 100% sensitivity for PHA detection. This cut-off was retested in a subsequent population (n = 43)., Results: A Liaison renin of 5 ng/L separated PRAs of ≤0.5 from ≥0.6 pmol/mL/h. The DSL method had greater scatter. In population 1 (18 PHA), cut-off ratios of >118 pmol/ng (Liaison) and >60 pmol/ng (DSL) gave specificities of 58.5% and 61%, respectively, with 100% sensitivity. If criteria for PHA included PAC ≥350 pmol/L and excluded β-blocked subjects, specificity increased to 95.1% and 90% for Liaison and DSL, respectively. In population 2 (6 PHA), specificities for Liaison and DSL ARRs were 86.4% and 78.3%. Using the ratio with PAC and β-blocker criteria, specificities for Liaison and DSL were 97.3% and 86.5%, respectively., Conclusions: The Liaison ARR used with PAC and β-blocker criteria provided an automatable alternative to identify the same patients as the PAC:PRA ratio.

Background: Measurement of B type natriuretic peptide and its N terminal prohormone (NTproBNP) can now be performed routinely by automated high-throughput immunoassays. The study compared measurement of NTproBNP with measurement of N terminal pro-atrial natriuretic peptide (NTproANP) for detection of ventricular systolic dysfunction in primary care., Methods: 734 subjects aged >45 years (349 men and 385 women, median age 58 years, range 45-89, interquartile range 51-67 years) from seven representative general practices attended for echocardiography with determination of ejection fraction and completed a questionnaire. Blood samples were collected into gel serum separation tubes (Becton-Dickinson, Franklin Lakes, New Jersey, USA), the serum separated and aliquots stored frozen at -70 degrees C until analyses. Samples were analysed for NTproBNP (Roche Diagnostics, Lewes, UK; coefficient of variation (CV) 3.2-2.4%) and for NTproANP (Biomedica, Vienna, Austria; CV 5.6-10.1%). Echocardiography was used as the diagnostic "gold standard", with ventricular systolic dysfunction defined as abnormal when there was an ejection fraction of

Objectives: Oral oestrogen preparations increase total cortisol concentration by increasing circulating cortisol-binding globulin (CBG) levels. Transdermal oestrogen treatments are being used increasingly in clinical practice. These topical preparations may have less of an effect on CBG and hence on total serum cortisol levels by reducing hepatic oestrogen exposure. The purpose of this study was to compare the effects of oral and topical oestrogen treatments on CBG, total serum cortisol and salivary cortisol levels., Design and Patients: This was a single-centre, cross-sectional study of 37 women aged 33 +/- 6 years (mean +/- SD). Fourteen women were using oral oestrogen therapy, eight were using transdermal therapy and 15 were oestrogen-naïve control subjects., Measurements: Following a screening visit, the subjects attended the endocrine investigation unit following an overnight fast. Blood and salivary samples were taken from 0830 to 0930 h between days 10 and 18 of the menstrual cycle (where appropriate)., Results: Total serum cortisol concentrations were 67% higher in those receiving oral oestrogen when compared to control subjects (660.9 +/- 89.9 vs. 395.4 +/- 53.2 nmol/l, P < 0.001). Values in those receiving transdermal oestrogen (334.7 +/- 72.0 nmol/l) were no different from the control group. CBG levels were higher in those on oral oestrogen therapy (110.9 +/- 19.6 mg/l, P < 0.001) when compared with either those on transdermal oestrogen (51.0 +/- 5.4 mg/l) or the control population (49.0 +/- 11.8 mg/l). Similar salivary cortisol concentrations were recorded in the three groups (controls 13.8 +/- 2.6 nmol/l, oral oestrogen 15.5 +/- 2.6 nmol/l, transdermal oestrogen 15.7 +/- 3.9 nmol/l)., Conclusions: Oral oestrogen-containing preparations increase total cortisol levels by increasing circulating CBG concentration. These effects were not seen in patients using transdermal oestrogen replacement. Although further studies are indicated, it is probably unnecessary to routinely discontinue transdermal oestrogen replacement when performing an assessment of the hypothalamic-pituitary-adrenal (HPA) axis or evaluating adequacy of hydrocortisone replacement.

Introduction: A poor comparison was seen between the Bayer Advia Centaur and the Roche Elecsys cortisol methods using samples sent to the laboratory for cortisol analysis. They were predominantly from patients attending the Endocrine outpatients clinic or patients in the intensive therapy unit. We investigated the effect of albumin concentration on the performance of both assays., Methods: For the samples used in the patient comparison, the laboratory database was searched for any concomitant albumin concentrations (Beckman LX20 BCP method). A series of recovery experiments were performed combining samples with normal albumin and undetectable cortisol concentrations with samples with detectable cortisol but low albumin concentrations., Results: Albumin concentration accounts for almost 50% of the variation in the difference between the two methods. The Bayer Advia Centaur method shows significant under-recovery at albumin concentrations lower than 24 g/L., Conclusion: This under-recovery will significantly affect the diagnosis of adrenal insufficiency in critically ill patients with low albumin concentrations.

Aims: To assess the screening characteristics and cost-effectiveness of screening for left ventricular systolic dysfunction (LVSD) in community subjects., Methods and Results: A total of 1392 members of the general public and 928 higher risk subjects were randomly selected from seven community practices. Attending subjects underwent an ECG, N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels, and traditional echocardiography (TE). A total of 533 consecutive subjects underwent hand-held echocardiography (HE). The screening characteristics and cost-effectiveness (cost per case of LVSD diagnosed) of eight strategies to predict LVSD (LVSD <45% on TE) were compared. A total of 1205 subjects attended. Ninety six per cent of subjects with LVSD in the general population had identifiable risk factors. All screening strategies gave excellent negative predictive value. Screening high-risk subjects was most cost-effective, screening low-risk subjects least cost-effective. TE screening was the least cost-effective strategy. NTproBNP screening gave similar cost savings to ECG screening; HE screening greater cost-savings, and HE screening following NTproBNP or ECG pre-screening the greatest cost-savings, costing approximately 650 Euros per case of LVSD diagnosed in high-risk subjects (63% cost-savings vs.TE)., Conclusion: Thus several different modalities allow cost-effective community-based screening for LVSD, especially in high-risk subjects. Such programmes would be cost-effective and miss few cases of LVSD in the community.

Aims: To define the N-terminal pro-brain natriuretic peptide (NTpBNP) normal range, assessing its cardiovascular screening characteristics in general population and higher risk subjects., Methods and Results: A total of 2320 subjects (1392 general population and 928 high-risk) > or =45 years old, selected randomly from seven community practices, were invited to undergo clinical assessment and echocardiography and to assess NTpBNP serum levels. Of these, 1205 attended. The NTpBNP normal range was calculated and its cardiovascular screening characteristics were assessed. Age (P<0.0001) and female gender (P<0.0001) independently predicted NTpBNP levels in normal subjects. In the general population, age- and gender-stratified normal NTpBNP levels gave a negative-predictive value (NPV) of 99% in excluding left ventricular systolic dysfunction, atrial fibrillation, and valvular heart disease, and a positive predictive value of 56% in detecting any cardiovascular disease assessed. In high-risk subjects, these values were 98 and 62%, respectively. Ninety-five per cent of subjects with NTpBNP levels over four times the normal had significant cardiovascular disease with the others having renal dysfunction., Conclusion: Normal NTpBNP levels should be stratified by age and gender. Normal NTpBNP levels give high NPV in excluding significant cardiovascular disease. Most subjects with raised NTpBNP levels and almost all subjects with NTpBNP levels over four times the normal have significant cardiovascular disease.

The Elecsys NT-proBNP assay is based on two polyclonal antibodies directed at residues 1-21 and 39-50 of the NT-proBNP molecule. Analytical performance was assessed using NCCLS protocol EP-5A using three serum pools in a preliminary study then as part of a multicentre evaluation (16 instruments in 8 hospitals). Using pools of 350 pg/l, 8700 pg/l and 13000 pg/l single site within run %CV was 0.7-1.6 (1010) and 1.2-1.5 (2010) and between run CV 5.3-6.7 (1010) and 4.4-5.0 (2010). In the multicentre evaluation within run CV was 1.0-2.5% with total imprecision 1.5-2.5% and between labs imprecision 3.8-4.0%. Functional sensitivity of <50 pg/l and measuring range to 35000 pg/l. There was excellent agreement between instrument platforms, y=0.97x+2.6; r=1.00 (n=215) for Elecsys 2010 (x) vs. Elecsys 1010 (y) and y=1.02x-0.3; r=1.00 (n=99) for Elecsys 2010 (x) vs. E 170 (y). Serum and heparin plasma samples showed good agreement but lower values were seen in EDTA plasma. Samples were stable for 7 days at room temperature; 21 days at 4 degrees C and for 5 freeze thaw cycles. Samples were obtained from a population of 1205 (671 male, 534 female) apparently healthy individuals screened by echocardiography and symptom questionnaire. There was poor correlation with NT-proANP (ELISA) (rs 0.33) and modest correlation with BNP (rs 0.89) with NT-proBNP values approximately 5 times greater than BNP (Biosite Triage). In a subset of 320 with normal ejection fraction (>50%) and no risk factors, NT-proBNP values increased with age and were higher in women than men.

Objective: To assess intraindividual variation of follicle stimulating hormone, luteinising hormone, estradiol, progesterone, inhibin A, and inhibin B in three successive ovulatory cycles correlated with transvaginal ultrasound monitored morphological changes in the ovary., Methods: Serial transvaginal color and pulsed Doppler ultrasound and serum hormone analysis were performed during midfollicular, periovulatory, and midluteal phase for three consecutive cycles in 19 patients with normal menstrual cycles., Results: Luteinising hormone and progesterone showed significant differences in the midluteal phase between the 1st and 2nd cycle (luteinising hormone p = 0.007 and progesterone p = 0.02). Progesterone showed a similar significant change (p = 0.013) between the 2nd and 3rd cycle. No significant differences were seen in the midfollicular or periovulatory phases or between the 1st and 3rd cycle., Conclusions: Luteal phase progesterone and luteinising hormone concentrations showed individual variation in successive cycles suggesting early or late corpus luteolysis. Follicular and periovulatory hormone levels were similar in subsequent ovulatory cycles.

Background: The fatty acid composition of adipose tissue triacylglycerol reflects, but is not identical to, the fatty acid composition of the habitual diet., Objective: We investigated whether the fatty acid composition of adipose tissue is explained by differences between fatty acids in early storage in adipose tissue after a meal., Design: Nine healthy men ate a meal containing several fatty acids. Blood samples were taken for 6 h after the meal from an arterialized hand vein and a vein draining the anterior abdominal subcutaneous adipose tissue., Results: Net storage of fatty acids in adipose tissue occurred between 1 and 4 h after the meal. In relation to the amount fed, storage of fatty acids differed (P < 0. 01) between classes (n-3 polyunsaturated < saturated < n-6 polyunsaturated < monounsaturated); oleic acid was stored in the greatest amounts. These differences agreed closely with published data, except for n-3 polyunsaturated fatty acids. The only individual metabolic step at which significant differences between fatty acids was shown was incorporation of fatty acids into chylomicron triacylglycerol. Differences between fatty acids in rate of extraction from chylomicron triacylglycerol and net uptake into adipose tissue in the postprandial period were significant (P < 0. 01), but not when expressed in relation to proportions in chylomicron triacylglycerol., Conclusions: The characteristic fatty acid pattern of adipose tissue may predominantly reflect the early metabolic handling of different fatty acids. Adipose tissue uptake of n-3 polyunsaturated fatty acids is slow in relation to that of other fatty acids.