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1.
The comparative effects of 3% saline and 0.5M sodium lactate on cardiac function:a randomised, crossover study in volunteers.
Nalos, M, Kholodniak, E, Smith, L, Orde, S, Ting, I, Slama, M, Seppelt, I, McLean, AS, Huang, S
Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine. 2018;(2):124-130
Abstract
OBJECTIVE To investigate the metabolic and cardiac effects of intravenous administration of two hypertonic solutions - 3% saline (SAL) and 0.5M sodium lactate (LAC). DESIGN, SETTING AND PARTICIPANTS A randomised, doubleblind, crossover study in ten human volunteers. Intravenous bolus of either SAL or LAC at 3 mL/kg over 20 min followed by a 2 mL/kg infusion over 60 min. MAIN OUTCOME MEASURES Acid base parameters and echocardiographic indices of cardiac function, cardiac output (CO), left ventricular ejection fraction (LVEF) and mitral annular peak systolic velocity (Sm) before and after infusion of SAL or LAC. RESULTS Despite haemodilution, we observed an increase in sodium (139 ± 2 mmol/L to 142 ± 2 mmol/L in both groups) and respective anions, chloride (106 ± 2 mmol/L to 112 ± 3 mmol/L) and lactate (1.01 ± 0.28 mmol/L to 2.38 ± 0.38 mmol/L) with SAL and LAC, respectively. The pH (7.37 ± 0.03 to 7.45 ± 0.03; P < 0.01) and simplified strong ion difference (SID) (36.3 ± 4.6 mmol/L to 39.2 ± 3.6 mmol/L; P < 0.01) increased during the LAC infusion. The pH was unchanged, but SID decreased during SAL infusion (36.3 ± 2.5 mmol/L to 33.9 ± 3.1 mmol/L; P = 0.01). Both solutions led to an increase in preload and cardiac function, CO (4.36 ± 0.79 L/min to 4.98 ± 1.37 L/ min v 4.62 ± 1.30 L/min to 5.13 ± 1.44 L/min), LVEF (61 ± 6% to 63 ± 8% v 64 ± 6% to 68 ± 7%). The averaged Sm improved in the LAC group as compared with the SAL group (0.088 ± 0.008 to 0.096 ± 0.016 v 0.086 ± 0.012 to 0.082 ± 0.012; P = 0.032). CONCLUSIONS The administration of SAL or LAC has opposing effects on acid base variables such as SID. Hypertonic fluid infusion lead to increased cardiac preload and performance with Sm, suggesting better left ventricular systolic function during LAC as compared with SAL. Lactated hypertonic solutions should be evaluated as resuscitation fluids.
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2.
Cardiovascular Risk Factors and White Matter Hyperintensities: Difference in Susceptibility in South Asians Compared With Europeans.
Sudre, CH, Smith, L, Atkinson, D, Chaturvedi, N, Ourselin, S, Barkhof, F, Hughes, AD, Jäger, HR, Cardoso, MJ
Journal of the American Heart Association. 2018;(21):e010533
Abstract
Background Cardiovascular risk factors vary between ethnicities but little is known about their differential effects on white matter hyperintensities ( WMH ), an indicator of brain aging and burden of cerebrovascular disease. Methods and Results Brain magnetic resonance imaging scans from 213 people of South Asian and 256 of European ethnicity (total=469) were analyzed for global and regional WMH load. Associations with cardiovascular risk factors and a composite cardiovascular risk score (National Cholesterol Education Programme Adult Treatment Panel III) were compared by ethnicity, diabetes mellitus, smoking, and hypertension status. Distributional patterns of WMH were similar by ethnicity but the vulnerability to specific risk factors differed. Associations between WMH and age or National Cholesterol Education Programme Adult Treatment Panel III scores were stronger in South Asians compared with Europeans. For instance, a year of age led to an excess of 3.8% (confidence interval=[0.2, 7.6]; P=0.04) of WMH load in frontal regions in South Asians compared with Europeans. In the diabetic subgroup, South Asians had more WMH than Europeans (+63.3%, confidence interval=[14.1, 133.9]; P=0.007), particularly in the deeper regions (+102% confidence interval=[24, 329]; P=0.004). In the population as a whole, diabetes mellitus was not, or only weakly, related to an increase in WMH volume (12.4%, confidence interval=[-10.7, 41.3]; P=0.32), and diabetes mellitus duration was a positive predictor of frontal periventricular WMH load in Europeans but not in South Asians. In turn, diastolic blood pressure was positively associated with WMH volumes in South Asians but not in Europeans. Hypertension was not associated with WMH load ( P=0.9). Conclusions Distribution patterns of WMH are similar in South Asians and Europeans but older age and higher cardiovascular risk are associated with more WMH in South Asians.
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3.
Multicentre factorial randomized clinical trial of perioperative immunonutrition versus standard nutrition for patients undergoing surgical resection of oesophageal cancer.
Mudge, LA, Watson, DI, Smithers, BM, Isenring, EA, Smith, L, Jamieson, GG, ,
The British journal of surgery. 2018;(10):1262-1272
Abstract
BACKGROUND Preoperative immunonutrition has been proposed to reduce the duration of hospital stay and infective complications following major elective surgery in patients with gastrointestinal malignancy. A multicentre 2 × 2 factorial RCT was conducted to determine the impact of preoperative and postoperative immunonutrition versus standard nutrition in patients with oesophageal cancer. METHODS Patients were randomized before oesophagectomy to immunonutrition (IMPACT® ) versus standard isocaloric/isonitrogenous nutrition, then further randomized after operation to immunonutrition versus standard nutrition. Clinical and quality-of-life outcomes were assessed at 14 and 42 days after operation on an intention-to-treat basis. The primary outcome was the occurrence of infective complications. Secondary outcomes were other complications, duration of hospital stay, mortality, nutritional and quality-of-life outcomes (EuroQol EQ-5D-3 L™, European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-OES18). Patients and investigators were blinded until the completion of data analysis. RESULTS Some 278 patients from 11 Australian sites were randomized; two were excluded and data from 276 were analysed. The incidence of infective complications was similar for all groups (37 per cent in perioperative standard nutrition group, 51 per cent in perioperative immunonutrition group, 34 per cent in preoperative immunonutrition group and 40 per cent in postoperative immunonutrition group; P = 0·187). There were no significant differences in any other clinical or quality-of-life outcomes. CONCLUSION Use of immunonutrition before and/or after surgery provided no benefit over standard nutrition in patients undergoing oesophagectomy. Registration number: ACTRN12611000178943 ( https://www.anzctr.org.au).
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4.
Drinks containing anthocyanin-rich blackcurrant extract decrease postprandial blood glucose, insulin and incretin concentrations.
Castro-Acosta, ML, Smith, L, Miller, RJ, McCarthy, DI, Farrimond, JA, Hall, WL
The Journal of nutritional biochemistry. 2016;:154-161
Abstract
Blackcurrants are rich in polyphenolic glycosides called anthocyanins, which may inhibit postprandial glycemia. The aim was to determine the dose-dependent effects of blackcurrant extract on postprandial glycemia. Men and postmenopausal women (14M, 9W, mean age 46 years, S.D.=14) were enrolled into a randomized, double-blind, crossover trial. Low sugar fruit drinks containing blackcurrant extract providing 150-mg (L-BE), 300-mg (M-BE) and 600-mg (H-BE) total anthocyanins or no blackcurrant extract (CON) were administered immediately before a high-carbohydrate meal. Plasma glucose, insulin and incretins (GIP and GLP-1) were measured 0-120min, and plasma 8-isoprostane F2α, together with arterial stiffness by digital volume pulse (DVP) was measured at 0 and 120min. Early plasma glucose response was significantly reduced following H-BE (n=22), relative to CON, with a mean difference (95% CI) in area over baseline (AOB) 0-30min of -0.34mmol/l.h (-0.56, -0.11, P<.005); there were no differences between the intermediate doses and placebo. Plasma insulin concentrations (AOB 0-30min) were similarly reduced. Plasma GIP concentrations (AOB 0-120min) were significantly reduced following H-BE, with a mean difference of -46.6ng/l.h (-66.7, -26.5, P<.0001) compared to CON. Plasma GLP-1 concentrations were reduced following H-BE at 90min. There were no effects on 8-isoprostane F2α or vascular function. Consumption of blackcurrant extract in amounts roughly equivalent to 100-g blackcurrants reduced postprandial glycemia, insulinemia and incretin secretion, which suggests that inclusion of blackcurrant polyphenols in foods may provide cardio-metabolic health benefits. This trial was registered at clinicaltrials.gov as NCT01706653.
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5.
Effects of early mother-infant intervention on outcomes in mothers and moderately and late preterm infants at age 1 year: a randomized controlled trial.
Ravn, IH, Smith, L, Smeby, NA, Kynoe, NM, Sandvik, L, Bunch, EH, Lindemann, R
Infant behavior & development. 2012;(1):36-47
Abstract
OBJECTIVE There is a dearth of knowledge about the effects of early interaction-based interventions on parenting and infant communication skills in moderately and late preterm infants. AIMS Assess in a RCT the effects of the Mother-Infant Transaction program (MITP) on maternal depression and stress, breastfeeding and mothers' perception of infant temperament; and MITP's impact on preterm infant communication skills at 12 months. METHODS Mothers/preterm infants (30-36 weeks) were randomly assigned to MITP (intervention group) or standard care (control group). Mean gestational age in the intervention group was 33.3±1.5 (n=56) and in the control group (n=50) 33.0±1.6. Outcomes were assessed by CES-D, Parenting Stress Index; WHO breast-feeding categories, Infant Behavior Questionnaire and The Pictorial Infant Communication Scales. RESULTS Intervention mothers reported significantly less postpartum depression one month after discharge (p=.04) and more breastfeeding at 9 months (p=.02). No significant group differences in favour of the intervention group were found on total parenting stress at 6 (p=.08) and 12 months (p=.46) or on perceived infant communication skills at 12 months (p=.86). The intervention mothers reported significantly less infant smile and laughter at 6 (p=.02) and 12 (p=.006) months and less motor activity at 12 months (p=.04). CONCLUSIONS The results suggest that MITP reduced postpartum depression and extended the period of breastfeeding, but did not support any positive effects of the intervention on self-reported maternal stress and perceived infant communication.
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6.
Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: a phase I, pharmacokinetic, and biologic correlative study.
Tolcher, AW, Ochoa, L, Hammond, LA, Patnaik, A, Edwards, T, Takimoto, C, Smith, L, de Bono, J, Schwartz, G, Mays, T, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2003;(2):211-22
Abstract
PURPOSE To determine the maximum tolerated dose and pharmacokinetics of cantuzumab mertansine, an immunoconjugate of the potent maytansine derivative (DM1) and the humanized monoclonal antibody (huC242) directed to CanAg, intravenously (i.v.) once every 3 weeks and to seek evidence of antitumor activity. PATIENTS AND METHODS Patients with CanAg-expressing solid malignancies were treated with escalating doses of cantuzumab mertansine administered i.v. every 3 weeks. The pharmacokinetic parameters of cantuzumab mertansine, the presence of plasma-shed CanAg, and the development of both human antihuman and human anti-DM1 conjugate antibodies also were characterized. RESULTS Thirty-seven patients received 110 courses of cantuzumab mertansine at doses ranging from 22 to 295 mg/m2. Acute, transient, and reversible elevations of hepatic transaminases were the principal toxic effects. Nausea, vomiting, fatigue, and diarrhea were common but rarely severe at the highest dose levels. Dose, peak concentration, and area under the concentration-time curve correlated with the severity of transaminase elevation. The mean (+/- SD) clearance and terminal elimination half-life values for cantuzumab mertansine averaged 39.5 (+/-13.1) mL/h/m2 and 41.1 (+/-16.1) hours, respectively. Strong expression (3+) of CanAg was documented in 68% of patients. Two patients with chemotherapy-refractory colorectal carcinoma had minor regressions, and four patients had persistently stable disease for more than six courses. CONCLUSION The recommended dose for cantuzumab mertansine is 235 mg/m2 i.v. every 3 weeks. The absence of severe hematologic toxic effects, preliminary evidence of cantuzumab mertansine tumor localization, and encouraging biologic activity in chemotherapy-refractory patients warrant further broad clinical development of this immunoconjugate in CanAg-expressing tumors.
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7.
Use of a fluorogenic septapeptide matrix metalloproteinase assay to assess responses to periodontal treatment.
Bhide, VM, Smith, L, Overall, CM, Birek, P, McCulloch, CA
Journal of periodontology. 2000;(5):690-700
Abstract
BACKGROUND Quantification of gingival crevicular fluid matrix metalloproteinase activity may provide improved assessment of periodontal disease status and response to treatment. A fluorogenic matrix metalloproteinase substrate assay (FSA) has been developed using a methoxycoumarin-containing septapeptide analog of the alpha2(I) collagen cleavage site. This substrate exhibits increased fluorescence following cleavage by many matrix metalloproteinases, and the enzyme activity can be readily estimated with a fluorimeter. Here we compared this assay with classical methods of periodontal assessment including bleeding on probing, crevicular fluid flow, and probing depth to assess its utility as an indicator of changes in periodontal status and treatment response. METHODS Complete measurements of probing depth were obtained for Ramfjord teeth on subjects who had been previously treated for periodontitis. Subjects were subsequently divided into groups based on existing periodontal disease severity: gingivitis (n = 21), stable periodontitis (n = 41), and severe periodontitis (n = 50). Crevicular fluid volume, bleeding on probing, and FSA were measured at each Ramfjord tooth or substitute. After baseline measurements, subjects received subgingival scaling and prophylaxis; 3 months later, they were reassessed. RESULTS FSA measurements were positively associated with severity of disease at baseline. After treatment there were substantial reductions of FSA in gingivitis (approximately 51%; P <0.01) and severe periodontitis (approximately 45%; P <0.001), but not in stable periodontitis (13%; P >0.2). All groups showed a positive association between FSA measurements and higher bleeding scores at individual sites. FSA measurements were also positively associated with crevicular fluid flow at baseline, but after treatment there was a approximately 67% decrease (P <0.01) in the highest crevicular fluid flow class. There were significant reductions of FSA at follow-up for sites with probing depths between 0 to 3 mm (23%; P <0.05) and 4 to 6 mm (31%; P <0.05). However, the largest reduction was for sites with probing depth between 7 to 9 mm (49%; P <0.001). CONCLUSIONS These results indicate that monitoring patients by measurement of matrix metalloproteinase levels in gingival crevicular fluid with the quenched fluorescent substrate assay provides estimates of inflammatory status, periodontal destruction, and response to treatment, especially in more severe periodontitis lesions.