Biomedical subjects

David R Sullivan

Publications and source records attributed to David R Sullivan.

11 recordsLinked to original sources

PubMed2006

Health benefits of herbs and spices: the past, the present, the future.

UNLABELLED: Herbs and spices have a traditional history of use, with strong roles in cultural heritage, and in the appreciation of food and its links to health. Demonstrating the benefits of foods by scientific means remains a challenge, particularly when compared with standards applied for assessing pharmaceutical agents. Pharmaceuticals are small-molecular-weight compounds consumed in a purified and concentrated form. Food is eaten in combinations, in relatively large, unmeasured quantities under highly socialised conditions. The real challenge lies not in proving whether foods, such as herbs and spices, have health benefits, but in defining what these benefits are and developing the methods to expose them by scientific means. CULTURAL ASPECTS: The place of herbs and spices in the diet needs to be considered in reviewing health benefits. This includes definitions of the food category and the way in which benefits might be viewed, and therefore researched. Research may focus on identifying bioactive substances in herbs and spices, or on their properties as a whole food, and/or be set in the context of a dietary cuisine. THE ROLE OF HERBS AND SPICES IN HEALTH: The antioxidant properties of herbs and spices are of particular interest in view of the impact of oxidative modification of low-density lipoprotein cholesterol in the development of atherosclerosis. There is level III-3 evidence (National Health and Medical Research Council [NHMRC] levels of evidence) that consuming a half to one clove of garlic (or equivalent) daily may have a cholesterol-lowering effect of up to 9%. There is level III-1 evidence that 7.2 g of aged garlic extract has been associated with anticlotting (in-vivo studies), as well as modest reductions in blood pressure (an approximate 5.5% decrease in systolic blood pressure). A range of bioactive compounds in herbs and spices have been studied for anticarcinogenic properties in animals, but the challenge lies in integrating this knowledge to ascertain whether any effects can be observed in humans, and within defined cuisines. Research on the effects of herbs and spices on mental health should distinguish between cognitive decline associated with ageing and the acute effects of psychological and cognitive function. There is level I and II evidence for the effect of some herbal supplements on psychological and cognitive function. There is very limited scientific evidence for the effects of herbs and spices on type 2 diabetes mellitus, with the best evidence being available for the effect of ginseng on glycaemia, albeit based on four studies. More research is required, particularly examining the effects of chronic consumption patterns. With increasing interest in alternatives to non-steroidal anti-inflammatory agents in the management of chronic inflammation, research is emerging on the use of food extracts. There is level II evidence for the use of ginger in ameliorating arthritic knee pain; however, the improvement is modest and the efficacy of ginger treatment is ranked below that of ibuprofen. More definitive research is required. PUBLIC HEALTH AND DIETARY IMPLICATIONS: Recommendations for intakes of food in the Australian guide to healthy eating do not yet include suggested intakes of herbs and spices. Future consideration should be given to including more explicit recommendations about their place in a healthy diet. In addition to delivering antioxidant and other properties, herbs and spices can be used in recipes to partially or wholly replace less desirable ingredients such as salt, sugar and added saturated fat in, for example, marinades and dressings, stir-fry dishes, casseroles, soups, curries and Mediterranean-style cooking. Vegetable dishes and vegetarian options may be more appetising when prepared with herbs and spices. FUTURE DIRECTIONS: As several metabolic diseases and age-related degenerative disorders are closely associated with oxidative processes in the body, the use of herbs and spices as a source of antioxidants to combat oxidation warrants further attention. Immediate studies should focus on validating the antioxidant capacity of herbs and spices after harvest, as well as testing their effects on markers of oxidation. This will work in parallel with clinical trials that are aiming to establish antioxidants as mediators of disease prevention. From a dietary perspective, the functionality of herbs and spices will be exposed through consideration of their properties as foods. As with most foods, the real benefits of including them in the diet are likely to emerge with a better understanding of the attributes of health that are best supported by food, and in methodological developments addressing the evidence base for their effects. These developments are well underway through evidence-based frameworks for substantiating health claims related to foods. At present, recommendations are warranted to support the consumption of foods rich in bioactive components, such as herbs and spices. With time, we can expect to see a greater body of scientific evidence supporting the benefits of herbs and spices in the overall maintenance of health and protection from disease.

Antioxidants↗

PubMed2006

A mild case of abetalipoproteinaemia in association with subclinical hypothyroidism.

Abetalipoproteinaemia (ABL), an extremely rare recessive disorder, is characterized by exceptionally low or undetectable concentrations of apolipoprotein (apo) B-containing lipoproteins. ABL results from mutations in the gene encoding microsomal triglyceride transfer protein (MTP), a chaperone that facilitates the transfer of lipids onto apoB. Patients with ABL often present in childhood with a range of symptoms including fat malabsorption and manifestations of fat-soluble vitamin deficiencies. We describe a patient with sub-clinical hypothyroidism and ABL found to be compound heterozygous for a novel splice site mutation of intron 1 (c.61 + 2T > C) and a single adenine insertion in MTP exon 4 (c.419-420insA) that results in a frameshift and a protein truncated at 140 amino acids.

Abetalipoproteinemia↗

PubMed2005

Plasma lipids predict myocardial infarction, but not stroke, in patients with established cerebrovascular disease.

AIMS: To evaluate the role of plasma lipids in recurrent vascular events, including stroke, among individuals with established cerebrovascular disease. METHODS AND RESULTS: Plasma total cholesterol, HDL cholesterol, and triglycerides were measured at baseline among individuals participating in the Perindopril Protection Against Recurrent Stroke (PROGRESS) study, a randomized clinical trial of blood pressure lowering among patients with previous stroke or transient ischaemic attack. A series of nested case-control studies were used to investigate the association between each of these lipid variables and the risk of subsequent haemorrhagic stroke, ischaemic stroke, myocardial infarction (MI), and heart failure. A total of 895 patients were selected as cases (83 haemorrhagic stroke, 472 ischaemic stroke, 206 MI, and 258 heart failure) and each was matched with one to three controls. After adjustment for other major cardiovascular risk factors, none of the lipid variables was associated with the risk of either stroke subtype. There were significant positive and negative associations for total cholesterol and HDL, respectively, with the risk of MI; the odds ratio comparing the highest and lowest thirds of each of these lipid variables was 2.00 (95% CI: 1.30-3.09) for total cholesterol and 0.58 (95% CI: 0.37-0.90) for HDL. HDL was inversely associated with the risk of heart failure; however, this result was of borderline statistical significance (P=0.05). CONCLUSION: Lipid variables are associated with the risk of MI, but not recurrent stroke, in patients with established cerebrovascular disease.

Aged↗

PubMed2005

Lipid-modifying drugs.

An elevated concentration of low-density-lipoprotein cholesterol (LDL-C) plays a causal role in the development of coronary heart disease and ischaemic stroke. Placebo-controlled intervention studies of statin drugs for lowering LDL-C provide clear evidence of cardiovascular disease prevention. LDL-C concentration below 2.5 mmol/L is an arbitrary goal, and recent trials support the benefit of achieving this goal, or even lower levels. Pharmacological treatment is warranted in patients with high absolute risk of future cardiovascular events. Effective monotherapy is available for predominant hypercholesterolaemia and predominant hypertriglyceridaemia, but combination therapy may be required for severe cases or in those with mixed hyperlipidaemia. Side-effects are infrequent and usually mild, but widespread use of lipid-modifying medication demands caution because of the possibility of muscle or liver dysfunction or drug interactions.

Anticholesteremic Agents↗

PubMed2005

Utility of brain natriuretic peptide (BNP) measurement in cardiovascular disease.

Cardiac failure is a prevalent and costly condition in Western society. The ageing of the population, together with current medical options which improve, rather than eradicate heart failure, lead to the projection that this problem will increase substantially in the foreseeable future. The availability of a simple test to assist the diagnosis and effective management of heart failure would greatly assist the clinical approach to this problem. This review examines the physiological basis for the measurement of natriuretic peptides as markers of the presence or risk of heart failure. It considers its use in the hospital and non-hospital setting and examines the cost-effectiveness of current assays. It is possible that in future natriuretic peptides may offer a form of treatment for heart failure, but this is beyond the scope of this review. Nevertheless, the review highlights the potential benefits of this group of tests in the management of heart failure.

Biomarkers↗

PubMed2005

The clinical and nutritional implications of lipid-lowering drugs that act in the gastrointestinal tract.

PURPOSE OF REVIEW: A new class of cholesterol-lowering therapy that reduces intestinal sterol absorption has recently been introduced. This increases the number of classes of lipid-lowering agents that directly affect gastrointestinal function and raises questions concerning the overall effect of these agents on absorption and nutritional status. RECENT FINDINGS: A recent assessment notes a paucity of information concerning the factors that affect the bioavailability and intestinal absorption of lipophilic nutrients. By contrast, the specificity of the mechanisms of action of new drugs acting on the gastrointestinal tract may circumvent some of the detrimental effects on nutrient and drug bioavailability that have been noted with older forms of treatment. SUMMARY: The clinical imperative for aggressive control of lipid and metabolic risk factors makes widespread use, alone or in combination, of lipid-lowering agents that affect the gastrointestinal tract seem increasingly likely. Whilst the opportunity for therapeutic synergy is attractive, care will be required to avoid interference with intestinal absorptive function.

Animals↗

PubMed2004

Meal-related increases in vascular reactivity are impaired in older and diabetic adults: insights into roles of aging and insulin in vascular flow.

A fatty meal induces vasodilatation (of both resting and stimulated forearm flow) in healthy young adults, an effect most likely mediated by the vasodilator actions of insulin. We therefore hypothesized that an impaired meal-related vascular response might be an in vivo marker of vascular insulin resistance, related to the presence of diabetes and/or higher age. Postprandial vascular responses were assessed in three groups of subjects: 15 Type 2 diabetic subjects (age 58 +/- 8 yr), 15 age-, gender-, and body mass index (BMI)-matched older control subjects (age 57 +/- 9 yr), and 15 healthy young control subjects (age 33 +/- 7 yr). Studies were carried out before and 3 and 6 h after a standardized high-fat meal (1,030 kcal, 61 g fat). Forearm microvascular flows were measured by strain gauge plethysmography and large-artery function by ultrasound. Resting blood flow and hyperemic area under curve (AUC) flow were not significantly different in diabetic subjects (resting 117 +/- 42% and AUC 134 +/- 46% of premeal values) compared with age-matched controls (resting 131 +/- 39% and AUC 134 +/- 47%); however, the response in diabetic subjects was blunted compared with young controls (resting 171 +/- 67% and AUC 173 +/- 99% of premeal values; P = 0.02 and P = 0.18, respectively). On multiple regression analysis, we found that increasing age (but not BMI or diabetes) was significantly associated with impaired postprandial vascular responses (resting: r = -0.4, P = 0.002; AUC: r = -0.4, P = 0.006). Therefore, meal ingestion results in impaired vasodilator responses in older nondiabetic and diabetic adults, related to aging rather than insulin resistance.

Adult↗

PubMed2003

Postprandial effects of dietary trans fatty acids on apolipoprotein(a) and cholesteryl ester transfer.

BACKGROUND: The consumption of trans fatty acids adversely affects fasting plasma lipoprotein concentrations. OBJECTIVE: This study aimed to investigate whether postprandial lipoprotein metabolism is affected by the consumption of trans fatty acids. DESIGN: In a randomized crossover study, 19 healthy men consumed fatty meals that were identical except that 10% of energy was provided as trans 18:1 acids in the trans meal and as oleic acid in the cis meal. RESULTS: The meals induced similar responses in plasma lipids. Cholesteryl ester transfer (CET) was activated after consumption of both meals (P < 0.0001); however, it was 28% higher after the trans meal than after the cis meal (280 +/- 129 compared with 219 +/- 116 nmol cholesteryl ester/mL plasma * 6 h; time x diet interaction: P < 0.0001). Plasma apolipoprotein(a) [apo(a)] concentrations remained constant; however, triacylglycerol-rich lipoproteins formed 4 h after ingestion of the trans meal contained a higher concentration of apo(a) than did those formed after ingestion of the cis meal (48.9 +/- 6.6 compared with 39.6 +/- 5.4 U/L; P < 0.02). The change in CET and in the proportion of plasma apo(a) in the triacylglycerol-rich lipoprotein fractions correlated with indexes of alimentary lipemia. CONCLUSIONS: Consumption of meals high in trans fatty acids results in higher CET and postprandial lipoprotein concentrations enriched in apo(a) than does consumption of meals free of trans fatty acids. This study highlights the importance of double-bond configuration in determining postprandial lipoprotein composition.

Adult↗

PubMed2003

Butyrylcholinesterase (BCHE) genotyping for post-succinylcholine apnea in an Australian population.

BACKGROUND: Measurement of plasma butyrylcholinesterase (BChE) activity and inhibitor-based phenotyping are standard methods for identifying patients who experience post-succinylcholine (SC) apnea attributable to inherited variants of the BChE enzyme. Our aim was to develop PCR-based assays for BCHE mutation detection and implement them for routine diagnostic use at a university teaching hospital. METHODS: Between 1999 and 2002, we genotyped 65 patients referred after prolonged post-SC apnea. Five BCHE gene mutations were analyzed. Competitive oligo-priming (COP)-PCR was used for flu-1, flu-2, and K-variant and direct DNA sequencing analysis for dibucaine and sil-1 mutations. Additional DNA sequencing of BCHE coding regions was provided when the five-mutation screen was negative or mutation findings were inconsistent with enzyme activity. RESULTS: Genotyping identified 52 patients with primary hypocholinesterasemia attributable to BCHE mutations, and in 44 individuals the abnormalities were detected by the five-mutation screen (detection rate, 85%). Additional sequencing studies revealed mutations in eight other patients, including five with novel mutations. The most common genotype abnormality was compound homozygous dibucaine and homozygous K-variant mutations. No simple homozygotes were found. Of the remaining 13 patients, 3 had normal BChE activity and gene, and 10 were diagnosed with hypocholinesterasemia unrelated to BCHE gene abnormalities. CONCLUSION: A five-mutation screen for investigation of post-SC apnea identified BCHE gene abnormalities for 80% of a referral population. Six new BCHE mutations were identified by sequencing studies of 16 additional patients.

Adolescent↗

PubMed2002

Effect of treatment on ventricular function and troponin I proteolysis in reperfused myocardium.

Effects of ischemia time and treatment interventions upon troponin I (TnI) proteolysis and function of reperfused myocardium were examined in isolated, perfused rabbit hearts. Hearts were randomized to 90 min aerobic perfusion, 15 min low-flow (1 ml/min) ischemia (I) and 60 min reperfusion (R) or 60 min low-flow I and 60 min R. Hearts subject to 60 min I and 60 min R received either no treatment, l -arginine treatment, or treatment with oxygen free radical (OFR) scavengers (mercapto-proponyl-glycine, catalase and superoxide dismutase). Hearts from cholesterol-fed rabbits were also studied after 60 min I and R. Isovolumic LV pressure and heart rate were recorded throughout and Western analysis of ventricular myocardium, using 3 specific antibodies, detected intact TnI (29 kDa) and TnI fragment (25 kDa). Hearts subject to 15 min I had minimal irreversible injury (TTC negative region=0.6+/-0.4% LV) but hearts subject to 60 min I had more extensive injury (TTC negative=40.7+/-5.8% LV). Recovery of rate-pressure product after 15 min I and 60 min R (56+/-9% of baseline) was better than after 60 min I and 60 min R (23+/-9%, P<0.01). Both l -arginine and OFR scavengers were associated with better recovery of function after 60 min I, (66+/-7% and 72+/-3% of baseline respectively, P<0.01 v no treatment) but cholesterol hearts had poor recovery after 60 min I (37+/-8%). The 25 kDa TnI (% total TnI immunoreactivity) was 8.7+/-0.9% in controls, 10.0+/-1.6% after 15 min I and 60 min R, and 17.4+/-2.4% after 60 min I and 60 min R (P<0.01 v controls and 15 min I). The proportion of 25 kDa TnI was increased in all hearts after 60 min I and did not change with treatment (l -arginine 16.8+/-1.8%, OFR scavengers 16.0+/-3.2%, cholesterol 14.0+/-1.9%). There was no relation between proportion of 25 kDa TnI and recovery of function. Samples from freshly excised rabbit hearts and human right atria also had 25 kDa TnI (relative intensities 8.5+/-2.3% and 5.1+/-2.6% respectively). Although TnI fragmentation increases after prolonged ischemia and reperfusion, the functional recovery of stunned myocardium is independent of degree of TnI fragmentation.

Animals↗

PubMed2002

Screening for cardiovascular disease with cholesterol.

BACKGROUND: Total cholesterol (TC) and lipoprotein measurements are among the major risk factors for cardiovascular disease (CVD). ISSUES: The massive (and increasing) disease burden associated with cardiovascular disorders justifies public health measures, such as screening, which may assist with the identification and treatment of individuals who have a high risk of developing these disorders. Whole populations are placed at risk by environmental factors such as dietary habits and exercise patterns, and this may be reflected by simple tests such as TC that largely depend on dietary consumption of saturated fat and cholesterol. On the other hand, identification of high-risk individuals within populations requires more specific tests such as measurement of cholesterol in lipoprotein fractions. This recognizes that the contribution of different risk factors may vary between individuals. Dietary and pharmacological interventions, particularly those that reduce low-density lipoprotein cholesterol (LDL-C), have been shown to prevent the onset or recurrence of CVD. CONCLUSIONS: It is desirable and justifiable to try to identify high-risk patients before the onset of clinical CVD because morbidity and mortality may occur as a consequence of the initial event. The relationship between the costs and the benefits of prophylactic interventions varies according to the extent to which clinical procedures, including laboratory testing, can estimate the level of cardiovascular risk. It can be argued that inappropriate cholesterol screening may have a negative effect on health economics and patient attitudes, but these problems appear easily surmountable. Techniques that enable the preclinical detection of CVD may help the process to strike a balance between public health initiatives that reduce the environmental factors responsible for the epidemic of CVD, and the strategies that are known to reduce event rates in high-risk individuals.

Cardiovascular Diseases↗