ORCID Profile
0000-0002-4895-1791
Current Organisation
James Cook University
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Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.JSS.2016.08.068
Abstract: The optimal hypothermic machine perfusion (HMP) solution has not yet been developed. An adenosine and lidocaine (AL) solution has been shown to be protective in cardiac preservation. The aim of the present study was to examine a modified AL solution with low Ca Twenty donation of organs after cardiac death porcine kidneys underwent HMP for 10 h (AL, n = 10 UW, n = 10) and then 2 h of normothermic reperfusion. Perfusion dynamics, functional parameters, histology, and real-time microdialysis were used to assess kidney responses and viability. During HMP, modified AL-perfused kidneys maintained higher flow rates (21.5 versus 17.9 mL/min/100 g, P = 0.01), with perfusion flow index during the first 3 h 25% greater than with UW (AL = 0.50 ± 0.2, UW = 0.40 ± 0.17 mL/min/100 g/mmHg P = 0.03), followed by an increase in UW kidneys which was not significantly different to AL over the remaining 7 h (0.54 versus 0.55 mL/min/100 g/mmHg, respectively). During warm reperfusion, there were no significant differences between the two HMP groups in creatinine clearance, oxygen, and glucose consumption between groups. Modified AL kidneys had significantly lower perfusate lactates (3.1 versus 4.1 mmol/L, P = 0.04) during reperfusion and lower cortical lactate levels (AL = 0.66 ± 0.31, UW = 0.89 ± 0.53 mM, P = 0.33). Histology showed similar degrees of reperfusion injury. We conclude that HMP with modified AL solution showed improved perfusion compared with UW and lower perfusate lactate levels during warm reperfusion. Further modification of the AL composition is warranted and may lead to more rapid kidney stabilization and improved graft viability assessment, potentially expanding donor pools.
Publisher: SAGE Publications
Date: 15-06-2021
DOI: 10.1177/1742271X211022402
Abstract: The study objectives were to develop standard charts for fetal renal artery blood flow to define normal ranges and to assess the reliability of the measurements. This prospective, longitudinal study reviewed 72 low-risk singleton pregnancies who had serial ultrasound examinations. Pulse wave Doppler was used to obtain the resistivity and pulsatility indices of the fetal renal arteries. Standard charts of the fetal renal arteries were created using mixed effects modelling and the intra- and interobserver reliability for the renal blood flow measurements was analysed. Standard charts of the normal ranges of the renal artery resistive index (RI) and pulsatility index (PI) of the fetal renal arteries were created. The 3rd, 5th, 10th, 50th, 90th, 95th and 97th centiles were calculated. The intraclass correlation coefficient was acceptable for intraobserver reliability (RI = 0.66, PI = 0.88) and poor for interobserver reliability (RI = 0.11, PI = −0.56). These novel charts demonstrate the change of the fetal renal artery blood flow during pregnancy. These may be used in clinical practice to detect variations from these normal ranges and be useful in future studies of kidney function projection.
Publisher: Inter-Research Science Center
Date: 14-09-2007
DOI: 10.3354/DAO01838
Abstract: Mounting evidence implicates the disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis, in global hibian declines and extinctions. While the virulence of this disease has been clearly demonstrated, there is, as yet, no mechanistic explanation for how B. dendrobatidis kills hibians. To investigate the pathology of chytridiomycosis, blood s les were collected from uninfected, aclinically infected and clinically diseased hibians and analyzed for a wide range of biochemical and hematological parameters. Here, we show that green tree frogs Litoria caerulea with severe chytridiomycosis had reduced plasma osmolality, sodium, potassium, magnesium and chloride concentrations. Stable plasma albumin, hematocrit and urea levels indicated that hydration status was unaffected, signifying depletion of electrolytes from circulation rather than dilution due to increased water uptake. We suggest that B. dendrobatidis kills hibians by disrupting normal epidermal functioning, leading to osmotic imbalance through loss of electrolytes. Determining how B. dendrobatidis kills hibians is fundamental to understanding the host-pathogen relationship and thus the population declines attributed to B. dendrobatidis. Understanding the mechanisms of mortality may also explain interspecific variation in susceptibility to chytridiomycosis.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.DCI.2017.08.018
Abstract: Temperature variability, and in particular temperature decreases, can increase susceptibility of hibians to infections by the fungus Batrachochytrium dendrobatidis (Bd). However, the effects of temperature shifts on the immune systems of Bd-infected hibians are unresolved. We acclimated frogs to 16 °C and 26 °C (baseline), simultaneously transferred them to an intermediate temperature (21 °C) and inoculated them with Bd (treatment), and tracked their infection levels and white blood cell profiles over six weeks. Average weekly infection loads were consistently higher in 26°C-history frogs, a group that experienced a 5 °C temperature decrease, than in 16°C-history frogs, a group that experienced a 5 °C temperature increase, but this pattern only approached statistical significance. The 16°C-acclimated frogs had high neutrophil:lymphocyte (N:L) ratios (suggestive of a hematopoietic stress response) at baseline, which were conserved post-treatment. In contrast, the 26°C-acclimated frogs had low N:L ratios at baseline which reversed to high N:L ratios post-treatment (suggestive of immune system activation). Our results suggest that infections were less physiologically taxing for the 16°C-history frogs than the 26°C-history frogs because they had already adjusted immune parameters in response to challenging conditions (cold). Our findings provide a possible mechanistic explanation for observations that hibians are more susceptible to Bd infection following temperature decreases compared to increases and underscore the consensus that increased temperature variability associated with climate change may increase the impact of infectious diseases.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2014
Publisher: Wiley
Date: 23-04-2020
DOI: 10.1002/PD.5701
Publisher: Georg Thieme Verlag KG
Date: 12-2007
Abstract: This study investigated the effects of cold water immersion on recovery from anaerobic cycling. Seventeen (13 male, 4 female) active subjects underwent a crossover, randomised design involving two testing sessions 2 - 6 d apart. Testing involved two 30-s maximal cycling efforts separated by a one-hour recovery period of 10-min cycling warm-down followed by either passive rest or 15-min cold water immersion (13 - 14 degrees C) with passive rest. Peak power, total work and postexercise blood lactate were significantly reduced following cold water immersion compared to the first exercise test and the control condition. These variables did not differ significantly between the control tests. Peak exercise heart rate was significantly lower after cold water immersion compared to the control. Time to peak power, rating of perceived exertion, and blood pH were not affected by cold water immersion compared to the control. Core temperature rose significantly (0.3 degrees C) during ice bath immersion but a similar increase also occurred in the control condition. Therefore, cold water immersion caused a significant decrease in sprint cycling performance with one-hour recovery between tests.
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.WNEU.2019.08.204
Abstract: To explain why some chronic subdural hematomas (CSDHs) grow and/or resorb, a physically decreasing outer membrane (OM) surface area (SA) to CSDH volume (V) ratio has been reexplored, and a critical CSDH size inferred (OM SA ≈ V). Gardner showed that since CSDH protein exceeded cerebrospinal fluid (CSF) protein, CSF→CSDH osmosis occurred across a semipermeable inner membrane (n = 1). By contrast, Zollinger and Gross demonstrated that serum→CSDH osmosis could also occur across the OM (n = 1). Notably, Weir refuted Zollinger and Gross by finding equal CSDH and serum total protein (n = 20) however, Weir did not refute Gardner. Although all extant mechanisms, especially rehemorrhages, explain CSDH growth, only OM SA ≥ V simultaneously permits resorption. We aimed to reevaluate the osmotic hypothesis. Paired serum and CSDH s les were measured in a prospective cohort. Results were consecutively obtained in 116 patients (87 men mean age, 73 ± 13 years). Serum osmolality and CSDH osmolality were similar (285.70 ± 7.99 vs. 283.85 ± 7.52 mmol/kg, respectively P = 0.11) and significantly correlated (r = 0.75, P < 0.0001). Serum total protein significantly exceeded CSDH total protein (66.6 ± 6.8 vs. 43.68 ± 20.24 g/L, P < 0.0001) as did serum albumin (35.62 ± 4.46 vs. 30.85 ± 8.5 g/L, P < 0.0001) and serum total globulins (31.5 ± 6 vs. 18.6 ± 11.4 g/L, P < 0.0001). Serum and CSDH proteins were not correlated (total protein: r = 0.003 albumin: r = 0.08 globulins: r = 0.21). Only crystalloids equilibrated. CSDH colloids were significantly decreased. CSDH dilution or colloidal flocculation is implied. CSDH dilution (by CSF→CSDH inner membrane [IM] osmosis or OM transudation/exudation) could favor CSDH growth, as would repeated OM hemorrhages. Contrariwise, isolated colloidal flocculation could favor CSDH shrinkage by OM CSDH→serum osmosis. The latter may result in OM SA ≥ V favorable for ultimate resolution. Our results refute Weir and Zollinger and Gross, but not Gardner. Osmotic gradients simultaneously exist for both CSDH growth and resorption. Each equilibrium could depend on each gradient relative to each IM/OM semipermeability.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 09-2021
Publisher: BMJ
Date: 07-07-2017
DOI: 10.1136/BJOPHTHALMOL-2016-308828
Abstract: Retinopathy of prematurity (ROP), a vasoproliferative disorder exclusive to premature infants is an important cause of childhood blindness. The number of premature infants surviving with this condition is expected to increase globally. Animal models of oxygen-induced retinopathy studies have shown vascular endothelial growth factor (VEGF) to be a key player in the pathogenesis of ROP. This has led to increased use of VEGF antagonist as an alternative treatment for ROP. The purpose of this systematic review is to determine the association between VEGF and ROP in human newborn. The literature review identified 12 studies to date which fulfilled the search criteria. Investigators used cord blood, serum, plasma and tissue s les to investigate the association between ROP and VEGF. Studies that measured VEGF in cord blood found mixed results, with low VEGF (at birth) associated with ROP in one study and no difference noted in two others. Mixed results were also seen in studies determining VEGF in postnatal venous s les. Four studies showed no difference in VEGF level between premature infants with and without ROP, one study showed an increased VEGF level in premature infants with ROP and another study found serum VEGF to be low in premature infants with ROP. The most recent study demonstrated an initial increase in serum VEGF followed by a decline at the time of treatment. These contradictory results indicate that we are yet to fully understand the role of VEGF in human premature infants and question the rationale of treating ROP with anti-VEGF. Anti-VEGF therapy results in systemic effect on serum VEGF levels for up to 2 months and this could have an effect on neurodevelopmental outcome. The effect of this on other developing organs is currently unknown. More studies are required to determine the mechanistic relationships between systemic VEGF and ROP in premature infants.
Publisher: Frontiers Media SA
Date: 31-01-2020
Publisher: Springer Science and Business Media LLC
Date: 05-09-2020
Publisher: Georg Thieme Verlag KG
Date: 2017
Abstract: Vascular endothelial growth factor-A (VEGF-A) plays an integral role in physiological and pathophysiological angiogenesis and has increasingly been implicated in the development of retinopathy of prematurity (ROP) in preterm infants. Application of intravitreal anti-VEGF is frequently used to treat ROP with little consideration given to the role of VEGF-A in neonatal growth and development. Previous studies have demonstrated systemic anti-VEGF persistence, reduced peripheral VEGF levels following treatment, and possible diagnostic and prognostic uses for VEGF-A determination. This study seeks to determine a normal range for serum VEGF-A (sVEGF-A) in healthy, term infants. The sVEGF-A levels were obtained from 32 neonates born at term infants (16 males and 16 females) using an enzyme-linked immunosorbent assay. No significant correlations were found between sVEGF-A levels and time of s le collection, birth weight, or gender. The median sVEGF-A level was 976 (394–1635) pg/mL (95% confidence interval for median: 496–1,318 pg/mL). This preliminary study determines a normal range for the sVEGF-A level in healthy, term neonates. This normal range will provide a tool to assist in the diagnosis, prognosis, and monitoring of treatment of infants with ROP.
Publisher: The Company of Biologists
Date: 11-07-2016
DOI: 10.1242/BIO.016790
Abstract: The persistent rise in global incidence of type 2 diabetes (T2D) continues to have significant public health and economic implications. The availability of relevant animal models of T2D is critical to elucidating the complexity of the pathogenic mechanisms underlying this disease and the implications this has on susceptibility to T2D complications. Whilst many high-fat diet-induced rodent models of obesity and diabetes exist, growing appreciation of the contribution of high glycaemic index diets on the development of hyperglycaemia and insulin resistance highlight the requirement for animal models that more closely represent global dietary patterns reflective of modern society. To that end, we sought to develop and validate a murine model of T2D based on consumption of an energy-dense diet containing moderate levels of fat and a high glycaemic index to better reflect the aetiopathogenesis of T2D. Male C57BL/6 mice were fed an energy-dense (ED) diet and the development of pathological features used in the clinical diagnosis of T2D was assessed over a 30-week period. Compared with control mice, 87% of mice fed an ED diet developed pathognomonic signs of T2D including glucose intolerance, hyperglycaemia, glycosylated haemoglobin (HbA1c) and glycosuria within 30 weeks. Furthermore, dyslipidaemia, chronic inflammation, alterations in circulating leucocytes and renal impairment were also evident in ED diet-fed mice compared with mice receiving standard rodent chow. Longitudinal profiling of metabolic and biochemical parameters provide support of an aetiologically and clinically relevant model of T2D that will serve as a valuable tool for mechanistic and therapeutic studies investigating the pathogenic complications of T2D.
Publisher: Springer Science and Business Media LLC
Date: 07-10-2022
DOI: 10.1038/S41390-021-01738-6
Abstract: Preterm birth is associated with the development of acute and chronic disease, potentially, through the disruption of normal gut microbiome development. Probiotics may correct for microbial imbalances and mitigate disease risk. Here, we used licon sequencing to characterise the gut microbiome of probiotic-treated premature infants. We aimed to identify and understand variation in bacterial gut flora from admission to discharge and in association with clinical variables. Infants born weeks gestation and g, and who received probiotic treatment, were recruited in North Queensland Australia. Meconium and faecal s les were collected at admission and discharge. All s les underwent 16S rRNA short licon sequencing, and subsequently, a combination of univariate and multivariate analyses. 71 admission and 63 discharge s les were collected. Univariate analyses showed significant changes in the gut flora from admission to discharge. Mixed-effects modelling showed significantly lower alpha ersity in infants diagnosed with either sepsis or retinopathy of prematurity (ROP) and those fed formula. In addition, chorioamnionitis, preecl sia, sepsis, necrotising enterocolitis and ROP were also all associated with the differential abundance of several taxa. The lower microbial ersity seen in infants with diagnosed disorders or formula-fed, as well as differing abundances of several taxa across multiple variables, highlights the role of the microbiome in the development of health and disease. This study supports the need for promoting healthy microbiome development in preterm neonates. Low ersity and differing taxonomic abundances in preterm gut microbiota demonstrated in formula-fed infants and those identified with postnatal conditions, as well as differences in taxonomy associated with preecl sia and chorioamnionitis, reinforcing the association of the microbiome composition changes due to maternal and infant disease. The largest study exploring an association between the preterm infant microbiome and ROP. A novel association between the preterm infant gut microbiome and preecl sia in a unique cohort of very-premature probiotic-supplemented infants.
Publisher: Wiley
Date: 22-04-2021
DOI: 10.1111/JPC.15492
Abstract: To determine the incidence rate of early‐onset neonatal sepsis (EONS) among term neonates (gestation greater than 37 weeks) admitted to the neonatal intensive care unit for suspected sepsis and the association of EONS with maternal fever (temperature greater than 38°C). A single‐centre retrospective cohort study of all term neonates (gestation weeks) admitted to and treated in the neonatal unit at the Townsville University Hospital between March 2015 and March 2020. Neonatal sepsis was confirmed with positive neonatal blood culture. Data on neonatal birth/stay and maternal pregnancy were collected from the electronic medical records and neonatal database. Data from 737 neonates who were admitted for treatment of EONS were analysed. Sixty % (426) reported maternal intrapartum fever, with 1.1% (5) of neonates developing blood culture‐proven sepsis. Forty % did not report intrapartum fever (311), with 3% (9) of neonates developing sepsis. As such, the sensitivity and specificity of maternal fever are 1.14% and 97%, respectively. The positive predictive value was 35.7%, and the negative predictive value was 40.1%. Fourteen neonates developed EONS, and all of them were symptomatic. Seventy‐eight % (334/426) of the women in the febrile group received epidural analgesia compared to 5% (16/311) in the afebrile group. Of the 95 neonates born to women with chorioamnionitis, one (1.0%) of the neonates born to women with chorioamnionitis developed sepsis. Intrapartum maternal fever is an unreliable predictor for EONS and leads to unnecessary antibiotic treatment. Symptoms in the neonate are a more reliable indicator of an ill neonate with blood culture‐proven sepsis.
Publisher: Informa UK Limited
Date: 11-09-2015
DOI: 10.3109/10641955.2015.1065883
Abstract: Nephrin is an integral part of podocytes that together with endothelial cells and the basement form the glomerular filtration barrier. Placental ischemia triggers a cascade of events that ultimately result in endothelial malfunction, hypertension, podocytopathy and fetal compromise. We review the literature to determine if urine nephrin measurements could serve as a useful biomarker to detect early podocyte injury in pre-ecl sia. Our search identifies eight studies published to date. The findings of these studies demonstrate that urine nephrin excretion plays a critical role in the pathogenesis of proteinuria during pre-ecl sia and that this is a good indicator of glomerular injury. There is thus an urgent need for a large multi-centre clinical study using standardized recruitment criteria to determine the full potential of this biomarker in clinical practice.
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.JTCVS.2010.04.040
Abstract: Rewarming and reanimating the donor heart from cold static storage predisposes the organ to injury and graft dysfunction. Our main aim was to investigate the effects of 5 minutes of continuous rewarming with a normokalemic, oxygenated, polarizing adenosine-lidocaine arrest solution after 6 hours of cold static storage (4°C) in adenosine-lidocaine or Celsior (Genzyme Corp, Cambridge, Mass) solutions. Male Sprague-Dawley rats (350-450 g, n = 40) were randomly assigned to one of 5 groups: (1) adenosine-lidocaine cold arrest with modified Krebs-Henseleit rewarming, (2) adenosine-lidocaine cold arrest with adenosine-lidocaine rewarming, (3) Celsior cold arrest with Celsior rewarming, (4) Celsior cold arrest with Krebs-Henseleit, and (5) Celsior cold arrest with adenosine-lidocaine arrest rewarming. Hearts were perfused in working mode, arrested (37°C), removed and stored for 6 hours at 4°C, reattached in Langendorff mode, and rewarmed for 5 minutes (37°C). Hearts were switched to working mode, and function was compared with prestorage values. Myocardial oxygen consumption and effluent lactate and pH values were measured during rewarming and recovery. Cold adenosine-lidocaine hearts rewarmed with Krebs-Henseleit recovered 40% aortic flow and 58% coronary flow at 60 minutes of reperfusion. Rewarming with adenosine-lidocaine arrest solution led to significantly higher aortic flow (63%) and coronary flow (77%) at 60 minutes. Cold Celsior hearts rewarmed with Celsior had 9 times higher effluent lactate values with acidosis (pH 6.5) during the last minute of rewarming compared with all groups, and this was associated with early myocardial, vascular, and electrical stunning. At 5 and 10 minutes of recovery, the aortic flow was 1.0 and 8 mL/min, respectively. If cold Celsior hearts were rewarmed with adenosine-lidocaine, they generated 18-fold higher aortic flow and 16-fold higher coronary flow at 5 minutes. At 60 minutes, cold Celsior with Celsior-rewarmed hearts recovered 35% aortic flow and 50% coronary flow compared with 44% aortic flow and 67% coronary flow (P < .05) for Celsior with adenosine-lidocaine-rewarmed hearts. Celsior with Krebs-Henseleit-rewarmed hearts recovered 39% aortic flow and 51% coronary flow and were not significantly different from Celsior-rewarmed hearts. The myocardial oxygen consumption in the last minute of rewarming was 1.6 times higher for cold adenosine-lidocaine hearts rewarmed with adenosine-lidocaine compared with cold Celsior and Celsior hearts (19 vs 12 μmol O(2)/min/g dry weight) along with low lactate values and no acidosis. Rewarming the rat heart after cold static storage in polarizing adenosine-lidocaine arrest solution resulted in significantly higher aortic flow, coronary flow, and cardiac output compared with that seen after Krebs-Henseleit or Celsior rewarming. Rewarming cold Celsior hearts with adenosine-lidocaine solution reduced stunning. Adenosine-lidocaine cardioplegia might offer a new reperfusion strategy after cold static storage.
Publisher: Wiley
Date: 27-11-2018
DOI: 10.1111/NEP.13520
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.MVR.2019.04.005
Abstract: The link between in utero and early life insults and the development of chronic illness remains to be fully understood, but there is increasing data to indicate that microvasculature pathology plays an important mechanistic role. Currently available data indicate that retinal microvasculature changes are detectable in children as young as six years of age, however, there are no data for younger children. We present retinal microvasculature measurement from the first two years of life. Retinal images suitable for analysis were available from 18 infants in our proof-of-concept study. The mean and standard deviation (SD) for birth weight and gestation was 3410 (384) g and 39.1(1.4) weeks, respectively. Retinal vessel calibres were summarized as the mean(SD) central retinal arteriolar equivalent (CRAE) at six months of age was 156 (32) μm, increased to 175 (75) μm by 12 months and a slightly declined by 24 months of age to 168 (50) μm. In a similar pattern, mean(SD) central retinal venular equivalent (CRVE) at six months was 211 (19) μm, increased to 238 (25) μm by 12 months of age followed by a slight decline at 24 months of age to 222 (36) μm. The arterio-venous ratio and tortuosity index remained the same at 6, 12 and 24 months. Findings from this study could help future investigators better understand early microvasculature changes and adaptation that occur early in life.
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.JTCVS.2008.06.031
Abstract: Currently, the safe human heart preservation time is limited to around 4 to 5 hours of cold ischemic storage. Longer arrest times can lead to donor heart damage, early graft dysfunction, and chronic rejection. The aim of this study was to examine a new nondepolarizing, normokalemic preservation solution with adenosine and lidocaine for as long as 6 hours of arrest at cold and warmer storage temperatures. Isolated perfused rat hearts (n = 87) were switched from working to Langendorff (nonworking) mode and arrested at 37 degrees C with 200-micromol/L adenosine and 500-micromol/L lidocaine in Krebs-Henseleit buffer (10-mmol/L glucose, pH 7.7, 37 degrees C) or with Celsior (Sangstat Medical Corp, Fremont, CA). Hearts were removed and placed in static storage at 4 degrees C for 2 and 6 hours or remained on the apparatus and were intermittently flushed at 37 degrees C every 20 minutes for 2 minutes at 68 mm Hg (average arrest temperature 28 degrees -30 degrees C) for 2 and 6 hours. We further investigated the effect of the warmer adenosine-lidocaine solution supplemented with 1- or 5-mmol/L pyruvate. Adenosine-lidocaine solution arrested hearts in 16 +/- 2 seconds (n = 32), whereas Celsior did so in 39 +/- 4 seconds (n = 23). After 2 hours of cold static storage, there were no functional differences between the adenosine-lidocaine and Celsior groups, with approximately 70% return of cardiac output. In contrast, after 6 hours of 4 degrees C storage, adenosine-lidocaine hearts had significantly higher functional recoveries (68% +/- 5% cardiac output) than Celsior hearts (47% +/- 14% cardiac output) during 60 minutes of reperfusion. In addition, Celsior hearts took 5 minutes longer to reanimate and showed early reperfusion arrhythmias. At warmer temperatures after 2 hours of arrest, adenosine-lidocaine and Celsior hearts were not significantly different, despite a 43% higher cardiac output in adenosine-lidocaine hearts (80% +/- 3% vs 56% +/- 12%). After 6 hours, adenosine-lidocaine hearts had recovered 55% +/- 3% of prearrest cardiac output, which increased significantly to 75% +/- 4% with addition of 1-mmol/L pyruvate. Adenosine-lidocaine with 1-mmol/L pyruvate hearts spontaneously recovered 106% heart rate, 93% to 105% developed pressures, 70% aortic flow, and 81% coronary flow. Coronary vascular resistance increased 1.7- to 1.9-fold during the 6-hour arrest. In contrast, Celsior hearts did not have return of aortic or coronary flow after 6 hours in these warmer conditions. A new nondepolarizing, normokalemic adenosine-lidocaine arrest solution in Krebs-Henseleit buffer with 10-mmol/L glucose was versatile at both 4 degrees C and 28 degrees C to 30 degrees C relative to Celsior, and the addition of 1-mmol/L pyruvate significantly improved cardiac output at warmer arrest temperatures. This new arrest paradigm may be useful in the harvest, storage, and implantation of donor hearts.
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.JTCVS.2011.05.023
Abstract: Most cardiac preservation solutions provide safe cold ischemic storage times for 4 to 5 hours. Our aim was to investigate the effects of 8 hours of cold static storage (4°C) using 2 normokalemic, polarizing adenosine-lidocaine (Adenocaine Hibernation Therapeutics Global Ltd, Kilquade, Ireland) solutions and to compare their functional recovery with hearts preserved in gold standard histidine-tryptophan-ketoglutarate (Custodiol-HTK Essential Pharma, Newtown, Pa) and Celsior (Genzyme, Cambridge, Mass) solutions. Male Sprague-Dawley rats (350-450 g) were randomly assigned to 1 of 4 groups (n = 8): (1) adenosine-lidocaine cardioplegia with low Ca(2+)/high Mg(2+) (2) 2× adenosine-lidocaine cardioplegia, low Ca(2+)/high Mg(2+), melatonin, and insulin (2× adenosine, lidocaine, melatonin, and insulin) (3) histidine-tryptophan-ketoglutarate solution or (4) Celsior. Hearts were perfused in working mode, arrested (37°C), removed, stored for 8 hours at 4°C, reattached in Langendorff mode and rewarmed for 5 minutes (37°C), and switched to working mode for 60 minutes. Myocardial oxygen consumption, effluent lactates, and troponin T levels were measured. Hearts preserved for 8 hours in adenosine-lidocaine and 2× adenosine, lidocaine, melatonin, and insulin returned 50% and 76% of aortic flow and 70% and 86% of coronary flow, respectively, at 60 minutes of reperfusion. In contrast, Custodiol-HTK and Celsior hearts returned 2% and 17% of aortic flow and 11% and 48% of coronary flow, respectively, at 60 minutes of reperfusion. Hearts preserved in adenosine-lidocaine and 2× adenosine, lidocaine, melatonin, and insulin returned 90% and 100% of developed pressures and 101% and 104% of heart rate, respectively. Hearts preserved in histidine-tryptophan-ketoglutarate failed to increase systolic pressure greater than 14 mm Hg (11% baseline) and diastolic pressure greater than 10 mm Hg (17% baseline), and recovered only 16% of heart rate. Hearts preserved in Celsior developed 70% of baseline systolic pressures and 86% recovery of heart rate. At 5 minutes of rewarming after cold storage, the myocardial oxygen consumption for hearts preserved in adenosine-lidocaine, 2× adenosine, lidocaine, melatonin, and insulin, Custodiol-HTK, and Celsior was 23.0 ± 5, 20 ± 4, 15 ± 1, and 10 ± 2 μmol O(2)/min/g dry wt, respectively, with corresponding lactate outputs of 1.8 ± 0.8, 1.5 ± 0.7, 2.6 ± 0.7, and 3.2 ± 1.4 μmol lactate/min/g dry weight. Troponin T was not detected in the coronary effluent of adenosine-lidocaine or 2× adenosine, lidocaine, melatonin, and insulin hearts, whereas Custodiol-HTK and Celsior hearts had troponin T levels of 0.08 and 0.24 μg/mL, respectively. We report a 78% return of cardiac output, 90% to 100% return of developed pressures, and 101% to 104% return of heart rate after 8 hours of cold static storage using normokalemic, adenosine, lidocaine, melatonin, and insulin preservation solution in the isolated rat heart compared with 55% cardiac output with polarizing adenosine-lidocaine cardioplegia alone, 4% cardiac output with Custodiol-HTK, and 25% cardiac output in Celsior preservation solutions.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2023
DOI: 10.1007/S10695-023-01191-8
Abstract: Reliable short-term chilled sperm storage is a critical prerequisite to using advanced reproductive techniques for captive breeding of barramundi (Asian sea bass Lates calcarifer ). Marine Ringer's solution (MRS) is a common non-activating medium (NAM) and has previously been used to store sperm from wild-caught barramundi. However, MRS-stored spermatozoa from captive-bred barramundi were observed to lyse within 30 min incubation. Therefore, this study aimed to optimize the composition of NAM for short-term chilled storage by characterizing and mimicking the biochemical profile of seminal and blood plasma of captive-bred barramundi. To further understand the effect of each component, osmolality was first examined to determine its effect on sperm viability. Thereafter, the effects of NaHCO 3 , pH, and Na + and K + concentrations on sperm motility were investigated. Optimization of the NAM formula was achieved through iterative adaptions. The increase in NAM osmolality from 260 to 400 mOsm/kg led to a significant improvement in sperm viability. Moreover, using HEPES instead of NaHCO 3 as buffering agent significantly enhanced sperm motility and velocity. As a result, sperm s les diluted with optimized NAM (185 mM NaCl, 5.1 mM KCl, 1.6 mM CaCl 2 ·2H 2 O, 1.1 mM MgSO 4 ·7H 2 O, 10.0 mM HEPES, 5.6 mM D + glucose, 400 mOsm/kg, pH 7.4) and stored at 4 °C showed no significant loss in total motility for up to 48 h and retained progressive motility for up to 72 h. The optimized NAM developed in this study significantly extended the functional lifespan of spermatozoa during chilled storage, permitting the ongoing development of advanced reproductive technologies for barramundi.
Publisher: Informa UK Limited
Date: 20-06-2018
DOI: 10.1080/14767058.2017.1338261
Abstract: The objective of this study was to investigate the association between prematurity, vascular endothelial growth factor A (VEGF-A), VEGFR-1 (soluble fms-like tyrosine kinase-1 (sFLT-1)) and retinopathy of prematurity (ROP). A cohort of 53 neonates (gestation <28 weeks) was recruited into this study and peripheral venous s les for VEGF and sFLT-1 measurement were obtained between gestational ages 32 The mean birth weight for the preterm neonates was 850 (178) g and the median gestational age was 26.4 [24.7-27.4] weeks. The median VEGF-A level was 1348 [608-2216] pg/mL and the median sFLT-1 level was 178 [103-244] pg/mL. Thirty-three neonates (33/53) developed various stages of ROP during their stay in the neonatal unit but only five neonates developed severe (stage 3) ROP needing treatment. The neonates with ROP were smaller (birth weight 801 (111) vs. 990 (175) g p < .0001), more preterm (gestation 25.4 [24.2-26.0] vs. 27.1 [26.8-27.9] weeks p < .0001) and received supplemental oxygen for a longer duration (1140 [218-1813] vs. 04 [40-434] hours p= .012). There was no statistically significant difference in the VEGF-A level or sFLT-1 levels between those who developed ROP and those who did not. There was a positive correlation between VEGF and both birth weight and gestation, respectively. There was no correlation between sFLT1 and birth weight or gestation. VEGF-A/sFLT-1 ratio in babies treated for ROP was significantly lower compared to those not treated (2.8 [1.0-5.7] vs. 9.9 [5.6-13.7] p = .04). A logistic regression model identified gestational age to be a statistically significant predictor of ROP (odds ratio 0.03 (0.001-0.550) p = .019). There is no direct correlation between systemic VEGF-A or sFLT-1 plasma levels and severity of ROP in extremely preterm neonates. The link between VEGF and ROP remains to be fully understood.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.JOCN.2019.05.058
Abstract: Chronic subdural haematoma (CSDH) is invariably classified as 'neurotrauma'. However, whilst a history of trauma/fall is frequent, it is usually distant, mild or even absent. Serum S-100β > 1.38 μg/L is associated with a 100% specificity for mortality oor outcome acutely after moderate-severe neurotrauma. Serum S-100β > 0.10 μg/L is used to screen mild neurotrauma cases for emergent neuro-imaging. Serum S-100 in controls is 0.057 μg/L. S-100β in serum or CSDH fluid (CSDH
Publisher: Springer Science and Business Media LLC
Date: 15-04-2020
DOI: 10.1007/S00467-020-04554-Y
Abstract: We carried out a study to determine the impact of prematurity on kidney development in the first 2 years of life. In this prospective study, extremely preterm neonates (gestation 28 weeks) were recruited and underwent assessments at 6, 12, and 24 months of age. A cohort of neonates born term were also recruited and followed up for 24 months. The primary outcomes measured in this study were total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) albuminuria and blood pressure measurements (all provided as mean (standard deviation)) were the secondary outcomes. Fifty-three premature and 31 term neonates (control) were recruited. At the age of 24 months (corrected age), infants born preterm had significantly smaller TKV (56.1 (9.4) vs. 64.8 (10.2) mL P = 0.006). There was no difference in eGFR. These preterm infants were smaller (11.25 (1.53) vs. 12.9 (1.8) kg P = 0.002) and shorter (83.8 (3.0) vs. 86.3 (3.4) cm P = 0.02) when compared with the control group. At 6, 12, and 18 months respectively, preterm infants had, relative to their height, significantly smaller kidney volumes (0.54 (0.1) vs. 0.59 (0.1) mL/cm, P = 0.05 0.61 (0.1) vs.0.71 (0.1) mL/cm, P = 0.003 and 0.67 (0.1) vs.0.76 (0.1) mL/cm, P = 0.006). Relative to body length, TKV in premature infants is smaller. Since length reflects adult body proportions more accurately than BSA, TKV to height ratio may be a more important measure in the child. Despite smaller TKV (and therefore fewer nephrons), infants born prematurely achieve similar eGFRs in the first 24 months of life, probably due to single-nephron hyperfiltration.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.JOCN.2016.09.008
Abstract: Prior studies have suggested that elevated serum Troponin-I (TnI) levels immediately after non-cardiac surgical procedures (8-40%) represent subclinical cardiac stress which independently predicts increased 30-day mortality. Routine post-operative TnI monitoring has therefore been suggested as a standard of care. However, no prior studies have focussed on elective degenerative spine surgery, whilst few have measured pre-op TnI. Further, prolonged prone positioning could represent an additional, independent, cardiac stress. We planned a prospective controlled cohort study of consecutive TnI levels in routine elective spine surgery for degenerative spine conditions, incorporating 3 groups: 'prone 2h' and 'supine' positioning. TnI levels (>0.04μg/L) were recorded immediately pre- ost-surgery, and by 24h of surgery. N=120 patients were recruited. Complete results were obtained in 92 (39 supine, 53 prone). No significant between-groups differences were observed in demographic or cardiovascular risk factors. Validated TnI-elevation by 24h was not observed in any group. Spurious elevations were recorded in one 'prone 2h'. One non-ST segment myocardial infarction (STEMI) occurred on day 7 without TnI elevation by 24h (prone>2h). There was no 30-day mortality. Despite a lower cut-off, no validated TnI elevation was observed in any group by 24h after surgery. One non-STEMI had not been associated with TnI-elevation by 24h. Immediately peri-operative cardiac stress therefore appeared comparatively rare in patients undergoing routine elective spine surgery. Further, prone positioning did not represent an additional, independent, risk. Routine immediately post-operative TnI monitoring in elective spine surgery therefore appears unjustified. Our study highlighted several caveats regarding consecutive TnI testing.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.HLC.2018.03.008
Abstract: Anti-myosin antibodies (AMAs) are often formed in response to myocardial infarction (MI) and have been implicated in maladaptive cardiac remodelling. We aimed to: (1) compare AMA formation in patients with Non-ST-Elevation MI (NSTEMI) and ST-Elevation MI (STEMI) (2) evaluate factors predicting autoantibody formation and, (3) explore their functional significance. Immunoglobulin M (IgM) and Immunoglobulin G (IgG) AMA titres were determined in serum s les collected at admission, 3 and 6 months post MI. The relationship between demographic and clinical data, and antibody formation, was investigated to determine factors predicting antibody formation and functional significance. Forty-three (43) patients were consecutively recruited 74.4% were positive for IgM at admission, compared with 23.3% for IgG. Mean IgG levels increased by 1.24% (±0.28) at 3 months, and 13.55% (±0.13) at 6 months post MI. Mean antibody levels were significantly higher in the NSTEMI cohort at both follow-up time points for IgG (p<0.001, p<0.0001), but not IgM (p=0.910, p=0.066). A moderately positive correlation between infarct size and increase in mean IgM concentration was observed at 3 months (r(98)=0.455 p=0.015). Anti-myosin antibody formation was not associated with an unfavourable outcome at follow-up. Anti-myosin antibodies are formed in a significant proportion of patients following MI, particularly among those with NSTEMI. While IgM levels fall after infarction, IgG levels increase and persist beyond 6 months of follow-up. This raises the possibility that they may contribute to long-term myocardial damage and dysfunction. Future research should focus on the specific epitopes that are targeted by these antibodies, and their functional significance. This may result in the emergence of novel therapies to attenuate cardiac dysfunction in MI patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2014
Publisher: Springer Science and Business Media LLC
Date: 02-03-2018
Publisher: Oxford University Press (OUP)
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 08-03-2021
DOI: 10.1186/S40748-021-00131-9
Abstract: The premature infant gut microbiome plays an important part in infant health and development, and recognition of the implications of microbial dysbiosis in premature infants has prompted significant research into these issues. The approaches to designing investigations into microbial populations are many and varied, each with its own benefits and limitations. The technique used can influence results, contributing to heterogeneity across studies. This review aimed to describe the most common techniques used in researching the preterm infant microbiome, detailing their various limitations. The objective was to provide those entering the field with a broad understanding of available methodologies, so that the likely effects of their use can be factored into literature interpretation and future study design. We found that although many techniques are used for characterising the premature infant microbiome, 16S rRNA short licon sequencing is the most common. 16S rRNA short licon sequencing has several benefits, including high accuracy, discoverability and high throughput capacity. However, this technique has limitations. Each stage of the protocol offers opportunities for the injection of bias. Bias can contribute to variability between studies using 16S rRNA high throughout sequencing. Thus, we recommend that the interpretation of previous results and future study design be given careful consideration.
Publisher: Elsevier BV
Date: 2019
Publisher: BMJ
Date: 12-2017
DOI: 10.1136/BMJOPEN-2017-019369
Abstract: Disorders of fetal growth, such as intrauterine growth restriction (IUGR) and large for gestational age (LGA), have been found to have a profound effect on the development of the fetal kidney. Abnormal kidney development is associated with hypertension and chronic kidney disease later in life. This study will use a novel ultrasound measurement to assess the renal parenchymal growth and kidney arterial blood flow in the fetus to evaluate the development of the fetal kidneys and provide an indirect estimate of nephron number. Measurements in normally grown, IUGR and LGA fetuses will be compared to determine if changes in renal parenchymal growth can be detected in utero. This longitudinal, prospective, observational study will be conducted over 12 months in the Ultrasound Department of the Townsville Hospital, Australia. The study will compare fetal renal parenchymal thickness (RPT) and renal artery Doppler flow between IUGR fetuses and appropriately grown fetuses, and LGA fetuses and appropriately grown fetuses between 16 and 40 weeks. The fetal RPT to renal volume ratio will also be compared, and correlations between RPT, renal parenchymal echogenicity, fetal Doppler indices and amniotic fluid levels will be analysed. This study was approved by the Townsville Health District Human Research Ethics Committee. The study results will form part of a thesis and will be published in peer-reviewed journals and disseminated at international conferences.
Publisher: CSIRO Publishing
Date: 22-12-0001
DOI: 10.1071/AN20393
Abstract: Context Transportation, a common practice in cattle production, activates the hypothalamo-pituitary-adrenal (HPA) axis, ultimately increasing glucocorticoids and altering the cellular immune system in cattle. Oxytocin attenuates the HPA axis in mammals. Intra-nasal oxytocin supplementation has been investigated in human and rodent models, revealing anxiolytic effects. The aim of this study was to assess the ability of exogenous oxytocin to mitigate stress and inflammatory responses in transported cattle. Aims We hypothesised that Bos indicus cattle treated with intra-nasal oxytocin would demonstrate more stable cortisol and inflammatory responses when subjected to handling and 6 h of road transportation compared with cattle treated with intra-nasal saline. Methods Thirty, Bos indicus steers were allocated to one of three treatments: (1) intra-nasal sterile saline and held in the yard for 6 h (S-NT n = 10), (2) intra-nasal sterile saline and transported for 6 h (S-T n = 10), and (3) intra-nasal oxytocin (0.3 IU/kg bodyweight) and transported for 6 h (OXT-T n = 10). Blood was collected at 0, 6, 48, and 72 h and analysed for haematological parameters, cortisol, glucose and lactate. Key results A treatment × time effect (P 0.05) was detected for lymphocytes and basophils, such that oxytocin helped maintain baseline counts. A treatment × time effect was detected for neutrophils and eosinophils such that counts were greater and lesser, respectively, directly following transport (P 0.01) for transported treatments. Total leukocyte counts were not different between treatments (P = 0.96). No differences were observed between treatments or over time for plasma cortisol concentration (P = 0.46). A treatment × time interaction (P 0.03) was detected for bodyweight such that transportation, independent of intra-nasal treatment, resulted in increased weight loss compared with the non-transported treatment. Conclusion Oxytocin altered circulating basophils in Bos indicus cattle exposed to short-duration transport. Although no effect on the HPA axis was detected via changes in cortisol concentration, road transport induced some signs of an acute inflammatory response directly following transportation. Implications Providing exogenous oxytocin improved the maintenance and recovery of some cellular immune system parameters in Bos indicus steers subject to short duration transport and more research is needed to explicate a more comprehensive understanding of such effects.
Publisher: Research Square Platform LLC
Date: 19-01-2021
DOI: 10.21203/RS.3.RS-144762/V1
Abstract: Background:The gut microbiome plays a critical role in the healthy development, immunity and metabolism of infants. Preterm birth disrupts microbiome development and can contribute to acute and chronic disease. To promote microbial and infant development, and to mitigate the risk of disease, premature infants may be treated with probiotics. Here we used 16S rRNA high throughout sequencing to characterize the bacterial microbiome of probiotic-supplemented premature infants. The study aimed to identify and understand variation in bacterial gut flora, including changes from admission to discharge, and the effect of several clinical variables using a combination of univariate and mixed effects analyses.Results: Infants born weeks gestation and g were recruited in North Queensland, Australia, with faecal s les collected at admission ( n = 71) and at discharge ( n = 63). Our research builds on previous research and supports significant changes over time in the preterm infant microbiome, and in response to several variables. Univariate analysis showed admission and discharge s les had significantly different microbial populations, with Staphylococcus enriched at admission and Enterobacter , Lactobacillus , Colstridium sensu stricto 1 and Veillonella at discharge. From the mixed effects modeling we observed significantly lower alpha ersity in infants diagnosed with either sepsis or retinopathy of prematurity (ROP), and those that only received formula milk. Chorioamnionitis, preecl sia, sepsis, necrotizing enterocolitis and ROP were also all associated with differential abundance of several taxa.Conclusions:Our study builds on previous research and supports significant changes in the preterm microbiome over time and in association with several factors. The fact that several associations were observed, and some in ways that counter previous work, highlights the complexity of microbiome ecology.
Publisher: Cambridge University Press (CUP)
Date: 15-04-2020
DOI: 10.1017/S204017442000015X
Abstract: Chronic kidney disease continues to be under recognised and is associated with a significant global health burden and costs. An adverse intrauterine environment may result in a depleted nephron number and an increased risk of chronic kidney disease. Antenatal ultrasound was used to measure the foetal renal parenchymal thickness (RPT), as a novel method to estimate nephron number. Foetal renal artery blood flow was also assessed. This prospective, longitudinal study evaluated the foetal kidneys of 102 appropriately grown and 30 foetal growth-restricted foetuses between 20 and 37 weeks gestational age (GA) to provide vital knowledge on the influences foetal growth restriction has on the developing kidneys. The foetal RPT and renal artery blood flow were measured at least every 4 weeks using ultrasound. The RPT was found to be significantly thinner in growth-restricted foetuses compared to appropriately grown foetuses [likelihood ratio (LR) = 21.06, P ≤ 0.0001] and the difference increases with GA. In foetuses with the same head circumference, a growth-restricted foetus was more likely to have a thinner parenchyma than an appropriately grown foetus (LR = 8.9, P = 0.0028), supporting the principle that growth-restricted foetuses preferentially shunt blood towards the brain. No significant difference was seen in the renal arteries between appropriately grown and growth-restricted foetuses. Measurement of the RPT appears to be a more sensitive measure than current methods. It has the potential to identify infants with a possible reduced nephron endowment allowing for monitoring and interventions to be focused on in iduals at a higher risk of developing future hypertension and chronic kidney disease.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.EJRAD.2017.09.017
Abstract: To determine the role of ultrasound imaging in evaluating fetal kidney growth. MEDLINE, CINAHL and EMBASE databases were electronically searched for studies between 1996 and January 2017 and limited to English language. Studies were included if they reported on an ultrasound technique to assess fetal kidney growth and they were not a case report or case series. There was independent selection of studies by two reviewers in consensus with one other reviewer. Data were extracted by one reviewer in consensus with two other reviewers. A total of 1785 articles were identified. The full text of 39 of these were assessed for eligibility for inclusion. Twenty-eight studies were then included in the review. Standard two dimensional (2D) fetal renal measurements are easy to perform, however, this review identified that most studies had some methodological limitations. The disadvantage with 2D and three dimensional (3D) fetal renal volumes are that they include the entire kidney and good reproducibility of 3D volumes has not yet been demonstrated. Currently there is limited research on fetal kidney growth in the setting of abnormal fetal growth. Research focussing directly on fetal kidney parenchyma and blood flow is scarce. Some nomograms of 2D and 3D fetal kidney size and volume have been developed. Kidney length is the most popular single fetal kidney measurement however, it does not seem to be a good indicator of growth. In IUGR fetuses, kidney length remained similar to appropriately grown fetuses whereas AP and TS dimensions were significantly decreased. New ultrasound techniques focusing on the parenchyma of the kidney and perfusion to the kidney should be explored as they may provide more meaningful information on kidney development in the fetus and future kidney function.
Publisher: Springer Science and Business Media LLC
Date: 04-02-2022
DOI: 10.1038/S41390-022-01970-8
Abstract: Preterm birth impairs nephrogenesis, leading to a reduced nephron endowment which is inextricably linked to hypertension and chronic kidney disease in adults. The aim of this study was to compare nephron endowment between preterm infants to that of intrauterine fetuses at the same gestational age (GA) using a novel indirect ultrasound measurement of the renal parenchymal thickness. We hypothesized that extrauterine and intrauterine renal parenchymal thickness would differ based on altered renal growth environments. In this observational study, appropriately grown preterm infants (birth weight of between the 5th and 95th percentile) born weeks, admitted to the neonatal department were eligible to participate. Renal parenchymal thickness of the infants was measured at 32- and 37-weeks postmenstrual age (PMA). These measurements were compared to the intrauterine renal parenchymal thickness of appropriately grown fetuses (control). At 32-weeks PMA, the preterm infants had a significantly thinner renal parenchyma compared to fetuses at 32-weeks GA suggesting they had less nephrons, however by 37-weeks there was no significant difference in renal parenchymal thickness. We propose that the differences in the extrauterine growth of the renal parenchyma in preterm infants may be due to a reduced number of nephrons and compensatory hyperfiltration. This article provides insight into the effects of prematurity on nephrogenesis by comparing extrauterine renal parenchymal growth of born preterm infants to the ideal intrauterine fetal growth. Renal parenchyma thickness measurement using ultrasonography is a novel non-invasive measurement of renal development for the determination of nephron endowment. Differences in the renal parenchymal thickness of the preterm infants may be due to a deficit in nephron number and compensatory hyperfiltration.
Start Date: 2019
End Date: 2023
Funder: National Health and Medical Research Council
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