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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.
Abdominal multiorgan procurement from slaughterhouse pigs: a bespoke model in organ donation after circulatory death for ex vivo organ perfusion compliant with the 3 Rs (Reduction, Replacement & Refinement).
BACKGROUND: Advances in organ preservation, reconditioning and assessment have been driven by the increasing necessity to utilise organs from extended criteria donors, particularly donors after circulatory death. Research efforts in this area have aided translation of machine perfusion technology into clinical practice. Pigs are anatomically and physiologically similar to humans and are an excellent model. However, conducting large animal experimental research is challenging and typically limited by ethical and economic constraints. Here we describe a reproducible, cost-effective multi-organ abdominal procurement model of porcine organs from the slaughterhouse. METHODS: Domestic pigs are electrically stunned and exsanguinated following the standard abattoir process. Via a longitudinal midline incision, the thoracoabdominal viscera are removed en bloc by incising along the anterior vertebral plane. The abdominal organs are isolated, perfused and separated preserving their respective vasculature, allowing individual organ use for specific experiments. RESULTS: The warm ischaemic time is kept between 15-30 minutes. Using this highly protocolized procurement technique we have procured 12 livers, 162 kidneys and 12 pancreata for research, the majority of which have been utilized for ex situ perfusion experiments. CONCLUSIONS: We have described a reliable and reproducible procedure for abdominal multi-organ procurement from slaughterhouse pigs.
Transplant and Recipient Factors in Prediction of Kidney Transplant Outcomes: A UK-Wide Paired Analysis.
BACKGROUND: In kidney transplantation, the relative contribution of various donor, procedure and recipient-related factors on clinical outcomes is unknown. Previous paired studies have largely focused on examining factors predicting early outcomes, where the effect of donor factors is thought to be most important. Here, we sought to examine the relationship between early and long-term outcomes in a UK-wide paired kidney analysis. METHODS: UK Transplant Registry data covering 24,090 kidney transplants performed between 2001-2018, where both kidneys from each donor were transplanted, were analysed. Case-control studies were constructed using matched pairs of kidneys from the same donor discordant for outcome, to delineate the impact of transplant and recipient factors on longer-term outcomes. RESULTS: Multivariable conditional logistic regression identified HLA mismatch as an important predictor of prolonged delayed graft function (DGF), in the context of a paired study controlling for the influence of donor factors, even when adjusting for early acute rejection. Prolonged DGF, but not human leucocyte antigen (HLA) mismatch, strongly predicted 12-month graft function, and impaired 12-month graft function was associated with an increased risk of graft failure. CONCLUSIONS: This study indicates prolonged DGF is associated with adverse long-term outcomes and suggests that alloimmunity may contribute to prolonged DGF by a mechanism distinct from typical early acute rejection.
Thyroid lobectomy for low-risk thyroid cancers.
BACKGROUND: The 2016 American Thyroid Association (ATA) guidelines proposed thyroid lobectomy for low-risk differentiated thyroid cancer (DTC); however, this approach is yet to be widely adopted. The aim of the study was to review our practice over three years following the publication of these guidelines identifying patients who underwent lobectomy-only for low-risk DTC in two regional units in the same multidisciplinary team (MDT). METHOD: A retrospective review of patients who were operated between January 2016 and December 2018 was carried out. RESULTS: In total, 288 patients undergoing thyroid surgery were included. The preoperative distribution of cytology was: Thy 1 or 2 in 46, THY3a in 57, THY3f in 154, THY4 in 18 and THY5 in 13 patients. Median size of nodules was 26mm (range 1-70mm). DTC was diagnosed in 95 patients (33%). Overall, 39% (n = 37) of patients underwent completion thyroidectomy according to ATA recommendations on size or adverse histological features. The only variable associated with likelihood of completion was tumour size (p
Fetal heart rate variability changes and fetal behavioural cycles during labour
In a study of 301 consecutive fetal heart rate (FHR) recordings of ≥6 h duration, consecutive episodes of low and high FHR variability consistent with cycles of quiet and active fetal behaviour were found in 38% of spontaneous and 68% of induced labours at term (P < 0.0001). Quiet periods (episodes of low FHR variability) had durations of 12-93 min (mean 25, SD 11 min) and in 48% of cardiotocographs (CTGs) these episodes had a long-term variability of <5 beats/ min. The implications of these findings are discussed in relation to the use of FHR recording for intrapartum surveillance. © 1986.
Liquid‐sensitive laryngeal receptors in the developing sheep, cat and monkey.
1. Action potentials were recorded from single afferent units of the superior laryngeal nerves in neonatal and adult sheep, cats and monkeys when liquids were passed over the laryngeal mucosa. 2. Two types of mucosal receptors, sensitive to water but not to isotonic saline, were found in each species from birth. The most common type of unit responded after a short latency (less than 1 sec), discharged maximally in the first 1‐3 sec and became inactive when the stimulus was withdrawn. The other type responded only after several seconds, the discharges gradually increasing in frequency and continuing after removal of the stimulus. 3. Reproducible responses were elicited by tactile stimulation of the laryngeal mucosa over the receptive field of each of the long‐latency units. Fewer than 50% of the short‐latency units were excited, the remainder responding only unreproducibly to firm pressure. 4. Short‐latency, but not long‐latency, units responded to milks, gastric contents, saliva and isotonic solutions of sugars. 5. The responses of long‐latency units to water were often modified by, but rarely dependent on, reflexly evoked activity in laryngeal muscles. 6. The conduction velocities of afferent fibres of water sensitive units ranged from 22 to 49 m/sec, and differed little from those of water‐insensitive laryngeal mechanoreceptors. 7. Histological examination of the laryngeal mucosa showed that taste buds were present in lambs from birth whereas they developed post‐natally in kittens and monkeys. The evidence suggests that taste buds were not associated with water‐sensitive units. © 1978 The Physiological Society
Pancreas and Islet Cell Transplantation
Type 1 diabetes mellitus (T1DM) affects millions of children worldwide, and its incidence is increasing. It is understood to be an autoimmune condition resulting in destruction of the insulin-producing beta cells within the pancreatic islets of Langerhans. The mainstay treatment is exogenous insulin replacement with the goal of controlling the disease in the acute stages and trying to maintain tight glycemic control to prevent the chronic complications of T1DM from developing in the longterm or reverse them if they have developed already. However, although novel types of insulin and sophisticated methods of insulin delivery are being developed, none of these can yet mimic the sophisticated mechanisms of glucose homeostasis within the normal pancreas, and insulin therapy fails to replace the other islet hormones essential for integrated glycemic control. Transplantation is currently the only form of treatment that offers reversal of T1DM by replacing the destroyed islets. This can be in the form of a major whole pancreas transplant or a minimally invasive pancreatic islet cell transplant. This chapter outlines the rationale, methods, results, and future opportunities for islet transplantation in children.
The risks of total pancreatectomy and splenic islet autotransplantation
The intraportal site is the most common site for islet transplantation. Many other sites have been tried experimentally, including the spleen, which has successfully lead to insulin independence in a number of animal models. Nevertheless, there are no detailed reports of total pancreatectomy and splenic islet autotransplantation in humans. Five patients underwent total pancreatectomy and splenic islet autotransplantation for chronic pancreatitis. Four patients had a pylorus-preserving total pancreatectomy and one patient a duodenal-preserving pancreatectomy. In three cases islets were embolized into both the portal vein and spleen. Two patients received splenic islet transplants alone. Islets were transplanted by retrograde venous infusion via the short gastric veins (n = 3), splenic vein stump (n = 1), and the left gastroepiploic vein (n = 1). The total volumes of transplanted pancreatic digest in those receiving combined intraportal and splenic autografts (n = 3) were 15.8, 13.0, and 13.5 ml. The volumes in those receiving a splenic-alone autograft (n = 2) were 12.0 and 5 ml. The mean rise in portal pressure was 18 cm of water. Complications related to the splenic autograft included a wedge splenic infarct, an emergency splenectomy, and a portal vein thrombosis in one patient having a combined intraportal and splenic autograft. Two patients developed insulin independence, two patients were still insulin independent at 1-year follow-up, and all had normal HbA1c levels (mean 5.6, range 5.2-6.3). Splenic islet autotransplantation, after total pancreatectomy, does lead to insulin independence. However, in our experience the combined procedure has a high morbidity because of splenic infarction and venous thrombosis.
Pancreatic islet autotransplantation combined with total pancreatectomy for the treatment of chronic pancreatitis - The Leicester experience
Islet autotransplantation offers the potential for preventing the surgically induced diabetes that is an inevitable consequence of total pancreatectomy. This paper describes the first islet autotransplant programme in the United Kingdom and the first series in the world to use the spleen as a site for the islet graft. Over an 11 month period, 7 patients underwent total pancreatectomy for chronic pancreatitis combined with a simultaneous islet autotransplant. All 7 patients had normal glucose-tolerance levels and normal C-peptide levels pre-operatively. In 6 patients, islets were embolized into the liver via the portal vein (median transplanted volume=8.5 ml). In addition, 3 patients received islets into the splenic sinusoids via a short gastric vein (median transplanted volume=4 ml). One patient received islets into the spleen alone. One patient died of a stroke 4 weeks post transplantation. Two patients have achieved insulin independence, with a further two patients achieving 'transient' insulin independence (<1 month). The remaining 2 patients, although requiring reduced insulin doses, have not achieved insulin-independence. However, all patients have C-peptide levels within the normal range. In trying to explain these findings, split proinsulin levels were measured and found to be elevated. High levels of split proinsulin cross react with the C-peptide assay and this would explain the falsely elevated C-peptide levels. Indeed insulin levels in these patients were all below the normal range. These findings would suggest that the use of C-peptide levels as the 'gold standard' for monitoring islet autograft function, may require reappraisal.
The influence of acute hypoxia and carotid body denervation on thermoregulation during non-rapid eye movement sleep in the developing lamb
We investigated the influence of ambient temperature on the thermoregulatory response to hypoxia in developing lambs before (at 4 and 14 days of age) and after (17 and 30 days of age) carotid body denervation (CBD). Lambs were studied during non-rapid eye movement sleep at thermoneutral (23-15°C) and cool (10-5°C) ambient temperatures, during normoxia and acute hypoxia (inspired oxygen content of 13%). Measurements of oxygen consumption, arterial partial pressures of O2 and CO2, colonic temperature, incidence of shivering and plasma concentrations of thyroid hormones, cortisol, insulin and glucose were made under each condition. Oxygen consumption was higher at cool compared with thermoneutral ambient temperatures and decreased during hypoxia during cooling at all stages. At 4 days of age, only one lamb shivered during cooling in normoxia, but 4 out of 12 lambs shivered during hypoxia and colonic temperature fell, significantly, by 0.2°C. At 14 days, 8 out of 12 lambs shivered during cooling, of which 6 continued to shiver during hypoxia but colonic temperature did not change significantly. Plasma triiodothyronine concentrations increased on cooling at 4 and 14 days, an affect that was inhibited by hypoxia at 4, but not 14 days of age. At 17 days of age, i.e. post-CBD, plasma thyroid hormone concentrations and oxygen consumption were lower during cold exposure compared with intact lambs at 14 days of age. In CBD lambs, imposing further hypoxia resulted in colonic temperature falling 0.6°C during cooling, with only 2 out of 10 lambs shivering. Plasma glucose and insulin, but not cortisol, concentrations decreased during hypoxia, irrespective of age or CBD. It is concluded that hypoxia has an important influence on metabolism and thermoregulation, which is modulated by age and environmental conditions. Compromised carotid body function, in lambs older than 2 weeks of age, can result in severe hypoxia and thermoregulatory dysfunction even with modest environmental cooling.
The clinical and economic advantages of remote, community-based physiological assessment
A prospective study documented the nutritional intakes of a large cohort of pregnant women living in Portsmouth and investigated the independent relationships of smoking, dietary intake and other maternal socio-economic factors on outcome and cardiorespiratory function of the child during sleep at home at three weeks and three months of age. Unattended overnight cardiorespiratory recording was performed and the data stored in local memory before transmission on demand via modem to Oxford next morning. The telemetry of the physiological data, entirely managed by part-time community nurses in Portsmouth, was very successful. Despite some losses, which included transmission failures, electrode or lead disconnection, and monitor malfunction, 92% of the physiological data were analysed at Oxford. Personalized physiological monitoring in the community provides an opportunity for new evidence bases that will enable a new level of individualized care.