Ik Robertson

Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease

The presence and progression of numerous diseases have been linked to deficiencies in antioxidant systems. The relationships between single nucleotide polymorphisms (SNPs) arising from specific antioxidant enzymes and diseases associated with elevated oxidative stress have been studied with the rationale that they may be useful in screening for diseases. The purpose of this narrative review is to analyse evidence from these studies. The antioxidant enzyme SNPs selected for analysis are based on those most frequently investigated in relation to diseases in humans: superoxide dismutase (SOD2) Ala16Val (80 studies), glutathione peroxidise (GPx1) Pro197Leu (24 studies) and catalase C-262T (22 studies). Although the majority of evidence supports associations between the SOD2 Ala16Val SNP and diseases such as breast, prostate and lung cancers, diabetes and cardiovascular disease, the presence of the SOD2 Ala16Val SNP confers only a small, clinically insignificant reduction (if any) in the risk of these diseases. Other diseases such as bladder cancer, liver disease, nervous system pathologies and asthma have not been consistently related to this SOD SNP genotype. The GPx1 Pro197Leu and catalase C-262T SNP genotypes have been associated with breast cancer, but only in a small number of studies. Thus, currently available evidence suggests antioxidant enzyme SNP genotypes are not useful for screening for diseases in humans.

Chickpeas may influence fatty acid and fiber intake in an ad libitum diet, leading to small improvements in serum lipid profile and glycemic control.

Optimal replacement macronutrient/s for dietary saturated fat to reduce cardiovascular disease risk remains controversial. Chickpeas are rich in dietary fiber and polyunsaturated fatty acids. This exploratory study, conducted from September 2004 to May 2005, assessed the effect of incorporating chickpeas in the ad libitum diet of 45 free-living adults. Participants consumed a minimum of 728 g of canned, drained chickpeas per week (the amount in four 300-g cans) as part of their habitual diet for 12 weeks (chickpea phase), followed by 4 weeks of habitual diet without chickpeas (usual phase). In the chickpea phase, mean dietary fiber intake was 6.77 g/day more and mean polyunsaturated fatty acid consumption (as a percentage of total fat) was 2.66% more (both P<0.001), causing the polyunsaturated to saturated fatty acids ratio to change from 0.39 to 0.47 (P=0.045). Serum total cholesterol and low-density lipoprotein cholesterol were 7.7 mg/dL (0.20 mmol/L) and 7.3 mg/dL (0.19 mmol/L) less, respectively, after the chickpea phase (P<or=0.01), fasting insulin was 0.75 microIU/mL (5.21 pmol/L) less (P=0.045), and the homeostasis assessment model of insulin resistance was 0.21 less (P=0.01). Univariate analysis revealed that dietary fiber had the greatest single effect, reducing serum total cholesterol by 15.8 mg/dL (0.41 mmol/L) (P=0.01). Polyunsaturated and saturated fatty acids had equivalent but opposing effects on serum total cholesterol and insulin. Larger studies on populations with greater degrees of hypercholesterolemia and/or hyperglycemia than the participants in this study are warranted.

Palliative care in end‐stage kidney disease

Patients with end‐stage kidney disease have significantly increased morbidity and mortality. While greater attention has been focused on advanced care planning, end‐of‐life decisions, conservative therapy and withdrawal from dialysis these must be supported by adequate palliative care incorporating symptom control. With the increase in the elderly, with their inherent comorbidities, accepted onto dialysis, patients, their nephrologists, families and multidisciplinary teams, are often faced with end‐of‐life decisions and the provision of palliative care. While dialysis may offer a better quality and quantity of life compared with conservative management, this may not always be the case; hence the patient is entitled to be well‐informed of all options and potential outcomes before embarking on such therapy. They should be assured of adequate symptom control and palliative care whichever option is selected. No randomized controlled trials have been conducted in this area and only a small number of observational studies provide guidance; thus predicting which patients will have poor outcomes is problematic. Those undertaking dialysis may benefit from being fully aware of their choices between active and conservative treatment should their functional status seriously deteriorate and this should be shared with caregivers. This clarifies treatment pathways and reduces the ambiguity surrounding decision making. If conservative therapy or withdrawal from dialysis is chosen, each should be supported by palliative care. The objective of this review is to summarize published studies and evidence‐based guidelines, core curricula, position statements, standards and tools in palliative care in end‐stage kidney disease.

A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy.

Abstract.  Khalafallah A, Dennis A, Bates J, Bates G, Robertson IK, Smith L, Ball MJ, Seaton D, Brain T, Rasko JEJ Launceston General Hospital (LGH), Australia; University of Tasmania, Australia; and Centenary Institute, University of Sydney, NSW, Australia) A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy. J Intern Med 2010; 268: 286–295.

Acute effects of food on postprandial blood pressure and measures of arterial stiffness in healthy humans

BACKGROUND Recent research suggests that central pulse pressure may be a better indicator of cardiovascular disease outcomes than brachial pressure. Little information is available regarding the effect of food intake on postprandial central pressure and other measures of arterial stiffness when measured with a noninvasive pulse wave analysis (PWA) technique. OBJECTIVE The objective was to investigate the effects of water and food plus water intake on brachial and central blood pressure (BP) and measures of arterial stiffness, including augmentation pressure and augmentation index, by using the PWA technique. DESIGN Measurements of BP and PWA were made at fasting and for 2 h after the intake of water or breakfast (1300 kJ) in random order in 35 subjects. RESULTS Baseline fasting measures of BP and arterial stiffness were not significantly different before the 2 interventions. Consumption of food plus water, compared with water alone, led to a significantly lower (all P < 0.01) brachial diastolic pressure (difference: -3.8 mm Hg), central BP (difference: systolic, -6.1 mm Hg; diastolic, -3.8 mm Hg), central pulse pressure (difference: -2.4 mm Hg), mean arterial pressure (difference: -4.6 mm Hg), augmentation pressure (difference: -2.9 mm Hg), and augmentation index (difference: -5.3 mm Hg). CONCLUSIONS Markers of central hemodynamics are sensitive to feeding state and therefore should be measured at fasting to avoid variability due to recent (within 2-3 h) food intake. This is especially important when measurements are repeated over time to assess the effect of medication or lifestyle changes on cardiovascular disease risk factors.

Helicobacter pylori, ethnicity, and the gastroesophageal reflux disease spectrum: a study from the East.

Background:  Ethnic differences in gastroesophageal reflux disease (GERD) and its complications as well as racial variations in the prevalence of Helicobacter pylori infection are well documented. Nevertheless, the association between reflux disease, H. pylori, and race has not been adequately explored.

Three-year follow-up of a randomised clinical trial of intravenous versus oral iron for anaemia in pregnancy

Background To date, there are no data available concerning the impact of iron therapy on the long-term well-being and health-related quality of life (HRQoL) in pregnancy. Objective To assess the long-term effect of iron therapy on HRQoL in pregnancy. Design This is a follow-up study conducted between January 2010 and January 2011 of an earlier randomised open-label clinical trial of intravenous and oral iron versus oral iron for pregnancy-related iron deficiency anaemia. We used a modified version of the SF-36 questionnaire together with the original prospective HRQoL data collected during and after pregnancy. Participants and interventions Of the original evaluable 183 pregnant Caucasian women randomised to receive oral iron or a single intravenous iron polymaltose infusion followed by oral iron maintenance, 126 women completed the follow-up HRQoL study. Methods The participants were followed up 4 weeks after treatment, predelivery and postdelivery for a median period of 32 months (range, 26–42) with a well-being and HRQoL questionnaire using a modified SF-36 QoL-survey and child growth charts as set by the Australasian Paediatric Endocrine Group (APEG). Results Patients who received intravenous iron demonstrated significantly higher haemoglobin and serum ferritin levels (p<0.001). There were strong associations between iron status and a number of the HRQoL parameters, with improved general health (p<0.001), improved vitality (physical energy) (p<0.001), less psychological downheartedness (p=0.005), less clinical depression (p=0.003) and overall improved mental health (p<0.001). The duration of breastfeeding was longer (p=0.046) in the intravenous iron group. The babies born in both groups recorded similarly on APEG growth chart assessments. Conclusions Our data suggest that HRQoL is improved until after pregnancy in anaemic pregnant women by repletion of their iron stores during pregnancy. About 80% of the intravenous iron group showed a maintained normal ferritin until delivery with long-term benefits. Further studies to confirm these findings are warranted.

Effects of a Controlled Diet Supplemented with Chickpeas on Serum Lipids, Glucose Tolerance, Satiety and Bowel Function

Objective: To compare the effect of a diet supplemented with chickpeas to a wheat-based diet of similar fibre content on serum lipids, glucose tolerance, satiety and bowel function. A third, lower-fibre wheat diet provided further information on dietary fibre quantity and bowel function and satiety. Method: Twenty-seven free-living adults followed two randomized, crossover dietary interventions each of five weeks duration. The chickpea diet included canned drained chickpeas, bread and shortbread biscuits containing 30% chickpea flour. The wheat diet included high-fibre wheat breakfast cereals and wholemeal bread. The diets were isoenergetic to the participants’ usual diet, matched for macronutrient content and controlled for dietary fibre. Following on from the second randomised intervention, a sub-group of 18 participants underwent a third, isoenergetic lower-fibre wheat diet that included low-fibre breakfast cereals and bread. Results: Repeated measures ANOVA revealed reductions in serum TC of 0.25 mmol/L (p < 0.01) and LDL-C of 0.20 mmol/L (p = 0.02) following the chickpea diet compared to the wheat. An unintended significant increase in PUFA and corresponding decrease in MUFA consumption occurred during the chickpea diet and statistical adjustment for this reduced but did not eliminate the effect on serum lipids. There was no significant difference in glucose tolerance. Perceived general bowel health improved significantly during the chickpea diet although there was considerable individual variation. Some participants reported greater satiety during the chickpea diet. Conclusions: The small but significant decrease in serum TC and LDL-C during the chickpea diet compared to the equivalent fibre wheat diet was partly due to unintentional changes in macronutrient intake occurring because of chickpea ingestion. If dietary energy and macronutrients were not controlled, chickpea consumption might result in greater benefits via influence on these factors.

Effect of atorvastatin on kidney function in chronic kidney disease: A randomised double-blind placebo-controlled trial

BACKGROUND The effect of atorvastatin on kidney function was assessed in patients with stages 2-4 chronic kidney disease. METHODS We conducted a randomised, double-blind, placebo-controlled trial in chronic kidney disease clinics in Northern Tasmania and enrolled 132 patients with serum creatinine levels >120 μmol/l, not taking lipid-lowering therapy and at all levels of proteinuria and serum cholesterol. Patients were randomly assigned to receive either 10 mg of atorvastatin/day (64) or placebo (68) and were followed with trial visits 3-monthly for a mean of 2.5 yrs. The primary outcome was the rate of both MDRD eGFR and Cockcroft-Gault creatinine clearance (C-G CrCl) decline. Analysis was based on intention to treat and included all patients that had at least one follow-up visit. RESULTS The rate of MDRD eGFR decline was 29% lower; 1.04 ± 3.84 vs. 1.47 ± 3.74 ml/min/1.73 m(2)/yr (P=0.53), and the C-G CrCl was 20% lower; 1.88 ± 5.07 vs. 2.36 ± 4.61 ml/min/1.73 m(2)/yr (P=0.58) in atorvastatin-treated, compared with placebo-treated patients. Although blood pressure decreased in both atorvastatin and placebo-treated groups there were no differences between groups. In addition, there was no difference in concomitant medication intake including angiotensin converting enzyme inhibitors and angiotensin receptor blockers between groups. CONCLUSIONS There was a trend toward a slower eGFR decline in the atorvastatin-treated group that did not reach statistical significance. This may have been due to the lack of power of the study. However, atorvastatin may have a renoprotective effect in those patients with chronic kidney disease and cardiovascular disease. This needs to be assessed in further studies.

The effect of 4-week chilli supplementation on metabolic and arterial function in humans

Objective:To investigate the effects of regular chilli ingestion on some indicators of metabolic and vascular function.Design:A randomized cross-over dietary intervention study.Setting:Launceston, Australia.Subjects:Healthy free-living individuals.Intervention:Thirty-six participants (22 women and 14 men), aged 46±12 (mean±s.d.) years; BMI 26.4±4.8 kg/m2, consumed 30 g/day of a chilli blend (55% cayenne chilli) with their normal diet (chilli diet), and a bland diet (chilli-free) for 4 weeks each. Metabolic and vascular parameters, including plasma glucose, serum lipids and lipoproteins, insulin, basal metabolic rate, blood pressure, heart rate, augmentation index (AIx; an indicator of arterial stiffness), and subendocardial-viability ratio (SEVR; a measure of myocardial perfusion), were measured at the end of each diet. In a sub-study, during week 3 of each dietary period, the vascular responses of 15 subjects to glyceryl-trinitrate (GTN) and salbutamol were also studied.Results:For the whole group, there were no significant differences between any of the measured parameters when compared at the end of the two dietary periods. When analysed separately, men had a lower resting heart rate (P=0.02) and higher SEVR (P=0.05) at the end of the chilli diet than the bland diet. In the sub-study, baseline AIx on the chilli diet was lower (P<0.001) than on the bland diet, but there was no difference in the effects of GTN and salbutamol between the two diets.Conclusion:Four weeks of regular chilli consumption has no obvious beneficial or harmful effects on metabolic parameters but may reduce resting heart rate and increase effective myocardial perfusion pressure time in men.