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Biomedical subjects

R S Tan

Publications and source records attributed to R S Tan.

At least 19 recordsLinked to original sources
PubMed2004

Role of androgens in mild cognitive impairment and possible interventions during andropause.

Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like PET scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.

Aging↗
PubMed2004

Glagov remodeling of the atherosclerotic aorta demonstrated by cardiovascular magnetic resonance: the CORDA asymptomatic subject plaque assessment research (CASPAR) project.

BACKGROUND: Aortic atherosclerosis and coronary artery disease (CAD) are closely linked. Early detection of aortic atherosclerosis with the adoption of appropriate preventive measures may therefore help to reduce mortality and morbidity related to CAD. Arterial remodeling, by which the wall adapts to physiological or pathological insults by a change in vessel size, is being increasingly recognized as an important aspect of atherosclerosis. In this prospective longitudinal study we used cardiovascular magnetic resonance (CMR) to detect aortic plaque and to study aortic wall remodeling in asymptomatic subjects. METHODS: We recruited 175 healthy volunteers (49 years, 110 men) and documented their cardiovascular risk profile. Each subject underwent echocardiogram (ECG)-gated T1-weighted spin-echo imaging of the infrarenal abdominal aorta at baseline and after 2 years. FINDINGS: Of the 175 subjects who volunteered at baseline, CMR was successful in 174 (99%), with one (0.6%) failure due to claustrophobia. At 2 years, follow-up scanning was performed in 169 subjects (97%). Infrarenal aortic plaque was identified at baseline in nine (5.2%) subjects. This was reconfirmed in all nine (100%) cases at 2-year follow-up. No new cases of infrarenal plaque were identified at follow-up. The signal characteristics of the plaque on the subtracted images of the Dixon method indicate that all plaques were fibrous. In the nine subjects with infrarenal plaque, the total plaque burden increased as assessed by the total wall volume (561 to 677 mm3, p = 0.0063). The total vessel volume also increased (1737 to 1835 mm3, p = 0.031) but there was no change in the total luminal volume (1175 to 1157 mm3, p = 0.29). CONCLUSIONS: Cardiovascular magnetic resonance detects subclinical aortic atherosclerosis, can follow plaque burden over time, and confirms the presence of Glagov remodeling with preservation of the lumen despite progression of plaque. Cardiovascular magnetic resonance is well suited for the longitudinal follow-up of the general population with atherosclerosis, may help in the understanding of the natural history of atherosclerosis, and in particular may help determine factors to retard disease progression at an early stage.

Aorta, Abdominal↗
PubMed2004

Risks of testosterone replacement therapy in ageing men.

Testosterone has been available to practitioners for several decades. However, testosterone prescriptions have increased in recent years partly because of the introduction of newer delivery systems that are topical and have good bioavailability. In the US alone, approximately 2 million prescriptions for testosterone were written in 2002. This represents a 30% increase from 2001 and a 170% increase from 1999. There has also been a 500% increase in prescription sales in the past 10 years. The rise in prescriptions may be in part due to the increasing recognition of hypogonadism in ageing males or andropause. Treatment relating to hypogonadism has relieved symptoms and improved the quality of life of many individuals. Epidemiological studies point toward an association with increased morbidity and mortality, with low testosterone states in ageing males. For example, there is a higher prevalence of depression, coronary heart disease, osteoporosis, fracture rates, frailty and even dementia with low testosterone states. Recently, there have been some concerns raised regarding the long-term safety of testosterone replacement therapy (TRT) from the Institute of Medicine. Current evidence suggests no causal relationship between prostate cancer and physiological dosing of testosterone, especially with careful selection and monitoring of patients. Cardiovascular risks have, overall, been neutral, although suggestions have been made that there are positive vasodilatory properties with testosterone. Mild eythrocytosis can be a common side effect of TRT, but thromboembolic events have rarely been reported in the literature. This paper addresses the evidence to date regarding the safety aspects of TRT. The medical-legal implications of TRT for men at this point in time is also discussed.

Adenocarcinoma↗
PubMed2004

Coronary artery disease: comprehensive evaluation by cardiovascular magnetic resonance imaging.

Cardiac magnetic resonance (CMR) imaging has emerged as an important non-invasive cardiac imaging modality. A versatile technique, it has the potential for comprehensive evaluation of coronary artery disease (CAD): cardiac morphology and function, myocardial perfusion, myocardial viability, coronary artery visualisation and atherosclerotic plaque characterisation. Some of these techniques--ventricular function and myocardial viability assessment--have already made mainstream clinical impact. Other techniques have yielded promising initial results, and will become increasingly accepted with technical refinement in scanner hardware and software. This article reviews the current status of clinical CMR imaging for diagnosis of CAD.

Coronary Artery Disease↗
PubMed2003

Role of androgens in mild cognitive impairment and possible interventions during andropause.

Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like positron emission tomography (PET) scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.

Aging↗
PubMed2003

A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease.

The male aging process brings about declines in hormonal function including a gradual decline in bioavailable testosterone levels. Animal studies suggest that testosterone modulates cognitive function through enhancing acetylcholine release and up-modulation of nicotinic receptors. Tau protein deposition is also affected by androgen supplementation in animals. We hypothesize that testosterone replacement in elderly hypogonadal males may improve cognition, in particular the visual-spatial domain. Thirty-six male patients with a new diagnosis of Alzheimer's disease had their total and bioavailable testosterone levels measured. None of the patients had been on acetylcholinesterase inhibitors. Ten of the 36 patients (28%) were deemed biochemically hypogonadal (total testosterone < 240 ng/dl or 7 nmol/l). Five of the hypogonadal patients were randomized to testosterone and five to placebo. Initial Alzheimer's Disease Assessment Scale cognitive subscale (ADAScog) and Mini Mental Status Examination (MMSE) ranged from 31 to 19 and from 17 to 22, respectively. The clock drawing test (CDT) and the pentagon-tracing portion of the MMSE were used as measures of visual-spatial abilities. Normal prostate-specific antigen (PSA) levels were essential before treatment with intramuscular testosterone, 200 mg every 2 weeks. Measurement of testosterone, complete blood count, lipids, PSA and neuropsychological cognitive tests were repeated at 3, 6, 9 and 12 months of treatment. In the testosterone-treated group, levels of total testosterone increased from a mean of 126.4 ng/dl to 341 ng/dl or 3.6 nmol/l to 9.7 nmol/l (p = 0.11). Bioavailable testosterone also increased from a mean of 48.7 ng/dl to 142 ng/dl or 1.39 nmol/l to 4.05 nmol/l (p = 0.10). PSA levels were also elevated from a mean of 0.98 to 1.37 ng/ml (p = 0.07). ADAScog improved from a mean of 25 to 16.3 (p = 0.02); MMSE improved from a mean of 19.4 to 23.2 (p = 0.02), CDT also improved from 2.2 to 3.2 (p = 0.07). One patient stopped treatment because of hypersexual behavior. The placebo-treated group deteriorated gradually. This small pilot study performed in aging male patients suggests that testosterone could indeed improve cognition, including visual-spatial skills in mild to moderate Alzheimer's disease.

Aged↗
PubMed2002

Impact of obesity on hypogonadism in the andropause.

Obesity is an issue that is increasingly affecting ageing men. With ageing, there is a decline in androgens as well. There are implications for the health of ageing men as a result of hypogonadism. Overall, there seems to be an inverse relationship between body mass index and testosterone levels, as is also demonstrated in our cross-sectional study. Obesity seems to depress the production of testosterone. It has been hypothesized that there is increased aromatization of testosterone to oestradiol and alteration of the hypothalamic-pituitary-adrenal axis in obese older men. Some hormones can affect obesity in ageing men including leptin, insulin, dehydroepiandrostenedione and growth hormone. The relationship of obesity to these hormones in ageing men will be reviewed. Testosterone replacement in ageing men can alter body composition whereby fat is exchanged for muscle. These studies will also be reviewed. Further studies in this field are recommended to evaluate long-term benefits and risks.

Aged↗
PubMed2001

The andropause and memory loss: is there a link between androgen decline and dementia in the aging male?

Studies demonstrate a decline in androgens with age and this results in the andropause. The objective of this paper is to review the literature on hormonal changes that occur in the aging males and determine if there are associations between decreased testosterone, dehydroepiandrosterone (DHEA) and decreased cognitive function. Trials of androgen replacement and its impact on cognitive function will also be analyzed. Method of analysis will be by a thorough search of articles on MEDLINE, the Internet and major abstract databases. Results of the author's own research in 302 men of the association of memory loss as a symptom in the andropause will be presented. In addition, the authors open trial of testosterone replacement in hypogonadic men with Alzheimer's disease will also be presented. The results of the author's trial will be compared with other investigators. High endogenous testosterone level predicted better performance on visual spatial tests in several studies, but not in all studies. Likewise, testosterone replacement in hypogonadic patients improved cognitive functions in some but not all studies. Testosterone has also been shown to improve cognitive function in eugonadal men. Several studies have shown that declines in DHEA may contribute to Alzheimer's disease and the results of double blind studies with DHEA replacement and its effect on cognition will also be presented. In summary, there is still no consensus that androgen replacement is beneficial in cognitive decline but this option may prove promising in some patients.

Aging↗
PubMed2000

Differential interleukin-10 expression in interferon regulatory factor-1 deficient mice during Plasmodium berghei blood-stage infection.

Mice deficient of functional interferon regulatory factor-1 (IRF-1-/-) by targeted gene disruption infected with a lethal murine malaria strain, Plasmodium berghei ANKA survived longer than its wild-type littermates despite the inability to induce appreciable amounts of interferon-gamma (IFN-gamma) and nitric oxide. In addition, infected IRF-1-/- mice displayed less organ injury with reduced necrosis and inflammation. Both wild-type and IRF-1-/- mice treated with exogenous interleukin-12 (IL-12) suffered extensive organ damage with corresponding up regulation of IFN-gamma, suggesting the pathogenic potential of IL-12 and IFN-gamma. IL-10 is a cytokine produced by CD4+ T lymphocytes belonging to the Th2 subset. Expression of IL-10 in the wild-type mice correlated with the severity of the infection, with higher mRNA expression towards the later stage of infection. In contrast to the wild-type mice, IL-10 levels in the IRF-1-/- mice were induced early in the infection and decreased gradually as the infection progressed. Both untreated and IL-12 treated wild-type mice appeared to follow a Th1-like immune response early in the infection and a Th2-like immune response later in the infection. However, the IRF-1-/- mice were able to launch an altered immune response with a Th2-like immune response early in the infection. These findings suggest that IL-10 expression in the IRF-1-/- mice during the early stage of P. berghei ANKA infection could play an important role in suppressing pathogenic effects of a cell mediated immune response and promoting protective immunity against the parasite.

Animals↗
PubMed1999

Altered immune response of interferon regulatory factor 1-deficient mice against Plasmodium berghei blood-stage malaria infection.

Nitric oxide (NO) is a short-lived biological mediator which can be induced in various cell types and is able to cause many metabolic changes in target cells. Inhibition of tumor cell growth and antimicrobial activity has been attributed to the stimulation of NO production by transcriptional upregulation of inducible nitric oxide synthase. In the present study, we used mice devoid of functional interferon regulatory factor 1 by targeted gene disruption (IRF-1(-/-)) to investigate the role of NO in the host immune response against blood-stage Plasmodium berghei ANKA infection. IRF-1(-/-) mice survived longer with a later onset of and a lower peak parasitemia despite the inability to produce appreciable levels of NO. The administration of exogenous interleukin-12 (IL-12) was able to prolong survival in the wild-type mice with an upregulation in the expression of both gamma interferon (IFN-gamma) and NO. However, the administration of IL-12 did not improve the survival of IRF-1(-/-) mice. These studies indicate that while IL-12 is able to mediate protection via an IFN-gamma- and NO-dependent pathway in the wild-type mice, such a protective mechanism may not be functional in the IRF-1(-/-) mice. Our results suggest that NO may not be essential for host immunity to the parasite and that IRF-1(-/-) mice are able to induce an IFN-gamma- and NO-independent mechanism against P. berghei infection.

Animals↗
PubMed1998

The Brugada syndrome in a Chinese population.

Sudden cardiac death has been reported in patients with a unique electrocardiographic (ECG) abnormality showing right bundle branch block and ST segment elevation in the precordial leads. This syndrome was first described by Brugada and Brugada and has not been previously described in a Chinese population. We report here the first three cases in Singapore. The first patient was a 49-year-old man who presented with syncope, associated with generalized convulsions. The second patient was a 25-year-old man who complained of palpitations but no syncope. The third patient was a 77-year-old man who presented with recurrent episodes of syncope and collapsed with ventricular fibrillation. All patients had no past cardiac or drug history of note. The neurological examination and investigations were normal. All three patients showed a unique right bundle branch block pattern with ST segment elevation in leads V1-3. The echocardiogram and 24-h ambulatory ECG monitoring, were normal. Single vessel disease was present in the third patient. Electrophysiological studies performed in all three patients were able to induce ventricular fibrillation. The patient with resuscitated cardiac death underwent an implantable cardioverter defibrillator implantation. The importance of this syndrome is that the recognition of the unique ECG pattern enables early identification and treatment of these patients.

Adult↗
PubMed1998

Testosterone replacement therapy. What is its potential in elderly men?

Currently, the use of testosterone replacement therapy in elderly men is not considered routine. However, the aging population makes it an increasingly important issue for primary care physicians, and therapy can be effectively managed in a primary care setting when indicated. Because of testosterone's potential side effects, therapy should be customized and patients must be carefully monitored. This treatment has tremendous potential, but further research is needed before routinely recommending it for hypogonadal elderly men.

Aged↗
PubMed1998

Goldberger's triad in dilated cardiomyopathy--can it predict the severity of left ventricular dysfunction?

Goldberger's triad is a specific, but relatively insensitive, electrocardiographic sign for dilated cardiomyopathy. To study the correlation between the presence of this sign and the severity of left ventricular dysfunction, the electrocardiograms and echocardiographically-determined left ventricular parameters of 17 patients (mean age 59.3 +/- 11.8 years) with dilated cardiomyopathy were examined. Five of the patients had Goldberger's triad. We found that the mean left atrial diameter, the mean left ventricular internal diameters (both end-systolic and end-diastolic) and the mean left ventricular ejection fraction of the group of patients with Goldberger's triad did not differ significantly from the group without. Coronary angiography revealed occult coronary artery disease in 5 of 12 patients. A larger, prospective study is required to verify our finding.

Cardiomyopathy, Dilated↗