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Biomedical subjects

David Talbot

Publications and source records attributed to David Talbot.

At least 19 recordsLinked to original sources

Optimization of deposition uniformity for large-aperture National Ignition Facility substrates in a planetary rotation system.

Multilayer coatings on large substrates with increasingly complex spectral requirements are essential for a number of optical systems, placing stringent requirements on the error tolerances of individual layers. Each layer must be deposited quite uniformly over the entire substrate surface since any nonuniformity will add to the layer-thickness error level achieved. A deposition system containing a planetary rotation system with stationary uniformity masking is modeled, with refinements of the planetary gearing, source placement, and uniformity mask shape being utilized to achieve an optimal configuration. The impact of improper planetary gearing is demonstrated theoretically, as well as experimentally, providing more comprehensive requirements than simply avoiding repetition of previous paths through the vapor plume, until all possible combinations of gear teeth have been used. Deposition efficiency and the impact of changing vapor plume conditions on the uniformity achieved are used to validate improved source placement. Uniformity measurements performed on a mapping laser photometer demonstrate nonuniformities of less than 0.5% for 0.75 m optics in a 72 in. (1.8 m) coating chamber.

Journal Article↗

Thermography and colour duplex ultrasound assessments of arterio-venous fistula function in renal patients.

Vascular and clinical assessments of arterio-venous fistula (AVF) function and access are important in patients undergoing or preparing to undergo renal dialysis. Objective assessment techniques include colour duplex ultrasound and more recently medical infrared thermography. Ideally, these should help assess problems relating to fistula failure or to vascular steal from the hand which can result from excessive fistula blood flow. The clinical value of thermography, as yet, has not been assessed for this patient group. The aims of this study were therefore to investigate the relationships between thermography skin temperature measurement and (a) quantitative ultrasound measurement of AVF blood flow, and (b) qualitative clinical assessment of vascular steal from the hands. Fifteen adult patients underwent thermal imaging of the upper limbs, colour duplex ultrasound to derive AVF blood flow from brachial artery blood flow measurements, and a clinical evaluation for vascular steal. Temperature measurements were extracted from the thermograms, including bilateral arm and hand (Fistula -- Non-Fistula) differences, for comparison with derived AVF blood flow and steal grading. Derived AVF blood flow ranged from 30 to 1,950 ml min(-1), with a mean rate close to one litre per minute. Thermography detected the warmer superficial veins in proximity to the patent fistulas, with bilateral differences in fistula region skin temperature correlated with derived AVF blood flow (using maximum temperature measurements the correlation was +0.71 [p < 0.01]; and using mean temperature measurements the correlation was +0.56 [p < 0.05]). When thermography measurements were compared with the clinical assessment of steal the mean hand temperature differences separated steal from non-steal patients with an accuracy of greater than 90%. In summary, we have now demonstrated the potential clinical value of medical infrared thermography for assessing AVF function in renal patients.

Adult↗

The effect of inadequate in situ perfusion in the non heart-beating donor.

In situ aortic perfusion in the nonheart-beating donors (NHBD) is an important procedure to reduce primary warm ischaemic injury prior to formal donor organ retrieval. It allows an interim period to obtain donor family consent and theatre preparation. This study describes our experience of inadequate aortic perfusions resulting from difficult aortic cannulations and associated adverse outcome despite reasonable viability tests. Since 1998, all NHBD in our institution are perfused in situ using a double balloon triple lumen (DBTL) catheter inserted through a femoral artery cut-down procedure. The DBTL catheter is positioned with distal occlusive balloon at the aortic bifurcation using the "pull-back" technique, the proximal occlusive balloon lies above the renal arteries. This provides selective aortic perfusion in particular the kidneys. Venous decompression using a femoral vein catheter enables a "two-way infusion system". Pre-transplant viability status of retrieved kidneys is determined by measuring pressure/resistance characteristics to the flow and biochemical markers for ischaemic injury. There were 90 NHBD renal transplants performed from 72 donors. Three renal transplants were carried out from three donors of ineffective in situ perfusion secondary to cannulation difficulties. Femoral cannulation was difficult as a result of extensive atherosclerosis of donor vessels. The comparison of allograft outcome from effective and ineffective in situ perfusion of donors showed high rate of primary nonfunction (PNF) from ineffective perfusion (chi-squared, P < 0.0001). The cases demonstrated poor outcome from ineffective perfusion related to the cannulation difficulties. Therefore a strict policy should be taken in cases where aortic cannulation and perfusion is inadequate, despite pretransplant assessment. In these circumstances, the primary warm ischaemia time should be extended to include this period of ineffective perfusion.

Adult↗

A case of acute humoral rejection in liver transplantation: successful treatment with plasmapheresis and mycophenolate mofetil.

We present a case of a 23-year-old female who underwent orthotopic liver transplantation (OLTx) for biliary atresia, 22 years after a failed Kasai operation. Unusually, her postoperative course was complicated by severe acute humoral rejection. In this case report, we discuss her management as well as the role of plasmapheresis in treating allograft dysfunction secondary to acute humoral rejection in liver transplant patients.

Acute Disease↗

Prospective study comparing three-dimensional computed tomography and magnetic resonance imaging for evaluating the renal vascular anatomy in potential living renal donors.

OBJECTIVE: To prospectively compare the accuracy of multislice spiral computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) in evaluating the renal vascular anatomy in potential living renal donors. SUBJECTS AND METHODS: Thirty-one donors underwent multislice spiral CTA and gadolinium-enhanced MRA. In addition to axial images, multiplanar reconstruction and maximum intensity projections were used to display the renal vascular anatomy. Twenty-four donors had a left laparoscopic donor nephrectomy (LDN), whereas seven had right open donor nephrectomy (ODN); LDN was only considered if the renal vascular anatomy was favourable on the left. CTA and MRA images were analysed by two radiologists independently. The radiological and surgical findings were correlated after the surgery. RESULTS: CTA showed 33 arteries and 32 veins (100% sensitivity) whereas MRA showed 32 arteries and 31 veins (97% sensitivity). CTA detected all five accessory renal arteries whereas MRA only detected one. CTA also identified all three accessory renal veins whereas MRA identified two. CTA had a sensitivity of 97% and 47% for left lumbar and left gonadal veins, whereas MRA had a sensitivity of 74% and 46%, respectively. CONCLUSION: Multislice spiral CTA with three-dimensional reconstruction was more accurate than MRA for both renal arterial and venous anatomy.

Donor Selection↗

Dual ipsilateral renal transplantation from a non-heart-beating donor.

A case is described where both kidneys from non-heart-beating (expanded criteria) donors were dual transplanted ipsilaterally. Although both kidneys passed viability tests on the Newcastle machine preservation system and biomarkers' evaluation, there were logistical issues where the cold ischaemic time was too protracted necessitating the transplantation of both kidneys into one recipient. The recipient had satisfactory outcome with the Cockcroft-Gault creatinine clearance of 72.47 (36.29 ml/min individual kidney glomerular filtration rate) suggesting beneficial use of sub-optimal organs to improve outcome.

Cadaver↗

Evaluation of eight preservation solutions for endothelial in situ preservation.

BACKGROUND: Non-heart-beating donors (NHBDs) have the potential to reduce the increasing numbers of patients on kidney and liver graft waiting lists. One problem observed with kidneys obtained from NHBDs is the endothelial injury seen on protocol core biopsies after implantation. We postulate that this is caused by a combination of warm ischemia, cold ischemia, and hypertonic citrate during in situ preservation (ISP) rather than hypothermic machine preservation. Our aim was to optimize ISP methods to preserve endothelial structure and function. METHODS: An animal model of ISP was used to compare the ability of eight different preservation solutions to protect mammalian vascular tissue exposed to a combination of warm and cold ischemia. Smooth muscle contractile function and endothelial dependent relaxation (nitric oxide production) were determined using an organ bath method. RESULTS: Bretchneider's HTK solution preserved the ability of endothelial tissue to relax vascular tissue in response to acetylcholine (91% relaxation vs. 17% saline control; ANOVA, P<0.001); in stark contrast, Marshall's solution performed no better than saline (15% relaxation vs. 17% saline control, P=NS). UW solution (80%) and a derivative lacking the starch colloid (70%) were comparable with HTK. Belzer-MPS (55%), Celsior (57%), and Perfadex (44%) showed a roughly equivalent level of endothelial preservation. Electron microscopy confirmed an anatomical loss of structure correlating with loss of function. CONCLUSIONS: ISP requires a large volume of fluid to be pumped at high flow rates. In this model, HTK retained a powerful ability to preserve endothelial structure and function during warm ischemia.

Adenosine↗

Graft function after kidney transplantation from non-heartbeating donors according to maastricht category.

PURPOSE: Donor shortages have led to some groups using alternative sources such as non-heartbeating donors (NHBDs). Kidneys from NHBDs suffer from warm ischemia at cardiac arrest which is reflected by acute tubular necrosis of the allograft, resulting in a period of delayed graft function. NHBDs are categorized by the circumstances surrounding the agonal events of death which reflect differences in the likelihood of ischemic injury to the kidney. In this study we determined the impact of ischemic injury on the renal function of kidneys procured from different categories of NHBDs. MATERIALS AND METHODS: From 1998 to 2003, 144 kidneys were procured from 72 NHBDs resulting in 93 transplants characterized into Maastricht categories II, III and IV NHBD renal transplants. Renal function after transplant was evaluated from the last dialysis until discharge from hospital, and then at 3 monthly intervals thereafter. RESULTS: Primary warm ischemic time is more prolonged in the uncontrolled donor (category II) than controlled donor (category III greater than IV). Delayed graft function occurs more frequently (Maastricht category II 83.8%, III 67.4% and IV 0%, ANOVA p <0.05) and the return to normal function is more prolonged in uncontrolled donors. This is illustrated by the greater incidence of acute tubular necrosis (Maastricht category II 81.1%, III 65.2% and IV 50.0%, ANOVA p = nonsignificant) in the kidney allograft. There was no difference in year 1 allograft survival (Maastricht category II 83.9%, III 92.5% and IV 100%, ANOVA p = nonsignificant). CONCLUSIONS: Early graft function is poorest in kidneys derived from Maastricht category II donors and best in category IV with III in-between. However, after 3 months the function of kidneys from all donors is the same.

Adult↗

Renal transplants from non-heart beating paracetamol overdose donors.

INTRODUCTION: Non-heart beating donors (NHBD) are widely encouraged to avert the critical shortage in the kidney donor pool. Ischaemic injury at the time of cardiac arrest in the NHBD is more pronounced and therefore the kidneys resulting are considered marginal. This review describes our experience with four kidneys from two controlled NHBDs who were exposed to paracetamol intoxication and subsequently were treated with mannitol prior to organ donation. MATERIALS AND METHOD: Two patients with fulminant liver failure following paracetamol overdose were referred as 'withdrawal of treatment' NHBD. As the two patients had developed hepatic encephalopathy they were treated with mannitol to reduce intra-cerebral oedema. The two donors were oligoanuric for at least 24 h prior to cardiac arrest. Following cardiac arrest, in situ perfusion was carried out and the kidneys were removed. One pair of kidneys were machine perfused while the second pair of kidneys were cold stored prior to transplantation. RESULTS: Pre-transplant assessment of NHBD kidneys resulted in three of four kidneys being transplanted. The NHBD kidneys exhibited a period of delayed graft function (DGF). The early transplant biopsies showed evidence of diffuse cytoplasmic vacuolation. These histological features disappeared with time and the renal function improved until the time of discharge. DISCUSSION: Non-heart beating donor kidneys are considered marginal and the effect of mannitol and paracetamol drug intoxication will induce reversible sub-lethal injury. A period of dialysis is inevitable in clearing the reactive intermediates of mannitol and paracetamol. The kidneys behaved as traditional controlled NHBD at time of discharge.

Acetaminophen↗

A report on the activity and clinical outcomes of renal non-heart beating donor transplantation in the United Kingdom.

The use of kidneys from non-heart beating donors (NHBDs) presents a paradox; whilst they provide more organs for transplantation, there is an increased risk of poor graft outcome, particularly in the short term. This study has highlighted the difference in early graft function and late graft survival between NHBD kidneys with short (controlled) and long (uncontrolled) warm ischaemic times. Whilst it would seem that it is preferable to use controlled donors only, their numbers are small. By employing a rational approach to the use of each of these types of kidney, such as structured viability assessment and risk analysis, it may be that the results of uncontrolled NHBD can be improved.

Adolescent↗

Transplantation from non heart beating donors in Newcastle upon Tyne.

Donor shortage has led transplant surgeons to reevaluate the concept of non heart beating donation. Organs from such donors are exposed to anoxia prior to harvesting and a portion of them will consequently present with delayed graft function. There is a need for dependable viability testing of organs from less than ideal NHBD donors and machine perfusion of kidneys provides such a tool. Our experience with own design machine perfusion device, studied parameters, perfusion solutions and outcomes is presented. Emphasis is placed on the incomparability of results obtained from different perfusion systems and the need to establish local criteria of kidney viability.

England↗

How to improve the quality of kidneys from non-heart-beating donors: a randomised controlled trial of thrombolysis in non-heart-beating donors.

BACKGROUND: The growth in the prevalence of end-stage renal failure has been accompanied with a rise in the waiting list for renal transplantation, which has not been matched by an increase in the kidney donor pool. Non-heart-beating donors (NHBD) offer a potential source of kidneys that are not currently being significantly used. Cardiac arrest for a protracted period of time leads to in situ thrombosis, and, as a consequence, the discard rates for harvested kidneys is higher than brain-stem-dead donors. METHODS: A double-blinded, randomised, controlled trial of streptokinase preflush or placebo for NHBD was performed. An initial 30 donors were entered into the study. After routine nephrectomy, NHBD kidneys were machine perfused as part of viability screening before transplantation. Kidneys were then transplanted within 24 hours of cardiac arrest. The primary objectives were the improvements of viability parameters (perfusion, enzyme levels, and histopathology) of the kidneys. The secondary objective was to increase the number of kidneys passing the viability tests and thus transplanted. RESULTS: The two groups of NHBD donors and their kidneys were similar in their descriptive epidemiologic characteristics. The NHBD kidneys from the streptokinase-treated donors had a better appearance at procurement (P<0.001) and performed better during machine preservation (P<0.001). Enzyme biomarkers present in the kidney perfusate were all significantly reduced by the use of streptokinase. These included glutathione S-transferase (P<0.001), fatty acid binding protein (P<0.001), and alanine aminopeptidase (P<0.001). However, although there was a higher proportion of kidneys transplanted through the use of streptokinase (63.6% with streptokinase vs. 42.6% with placebo), this did not achieve significance. There was no difference with respect to postoperative bleeding and transfusion requirements in the recipient whether streptokinase preflush or placebo was used. CONCLUSION: This study using streptokinase preflush in the NHBD was found to improve the condition of the kidneys retrieved. The improvement in the quality of the donor kidneys was not associated with an increased morbidity in the recipient.

Alanine Transaminase↗

Do tissue damage biomarkers used to assess machine-perfused NHBD kidneys predict long-term renal function post-transplant?

BACKGROUND: Renal transplantation in many units is limited by the availability of donor organs. Kidneys obtained from non-heart-beating donors (NHBD) represent an important resource, with the potential to substantially increase the available donor organ pool. Such kidneys are associated with increased warm ischaemic tissue injury which may be assessed by hypothermic machine perfusion. Within our transplant centre, a key component of such damage assessment and viability screening involves the quantification of the tissue damage biomarkers glutathione S-transferase in kidney perfusates. METHODS: Since 1998, 126 NHBD kidneys were machine-perfused prior to implantation, resulting in 74 transplants. Kidney perfusate samples were assayed for glutathione S-transferase in "real time", and alanine aminopeptidase and fatty acid binding protein in "retrospect". RESULTS: The pre-transplant concentration of these tissue injury biomarkers determined pre-transplant did not correlate with subsequent longer-term renal function, as assessed by measurement of serum creatinine (tGST: Spearman correlation r=-0.02; Ala-AP: r=0.02; H-FABP: r=-0.05) and creatinine clearance (tGST: r=0.08; Ala-AP: r=-0.02; H-FABP: r=0.14) for those kidneys that had passed their viability tests. CONCLUSIONS: Thus whilst these biomarkers may represent reliable pre-transplant indicators of immediate kidney viability and short-term kidney function, they do not predict the efficacy of renal function in the longer term.

Biomarkers↗