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Biomedical subjects

Samuel D Vasikaran

Publications and source records attributed to Samuel D Vasikaran.

16 recordsLinked to original sources

B-vitamins reduce plasma levels of beta amyloid.

Elevated plasma homocysteine (tHcy) is a risk factor for Alzheimer's disease (AD), and thus B vitamins may have a role in the prevention of AD. The objective of this study was to determine if tHcy lowering vitamins decrease the circulating levels of A-beta protein 1-40 (A beta 40). We randomized 299 older men to treatment with 2mg of folate, plus 25mg of B6 and 400 microg of B12, or placebo. After 2 years of treatment the mean (S.E.) increase of A beta 40 was 7.0 pg/ml (8.4) in the vitamin group (4.9%), and 26.8 pg/ml (7.7) (18.5%) in the placebo group. We conclude that B vitamins may decrease the plasma level of A beta 40 and have a role in the prevention of AD.

Aged↗

Urinary NTX results rarely alter the clinical management of patients with osteoporosis in the tertiary hospital.

AIM: Urinary levels of cross-linked N-terminal telopeptide of type I collagen (NTX) are used as a marker of bone resorption and are useful for monitoring response of patients treated with anti-resorptive agents. We aimed to determine how urinary NTX results alter clinical decision making by physicians treating patients with osteoporosis in a tertiary hospital setting. METHODS: We reviewed patient notes of all new NTX requests in 2002 and 2003 with at least one subsequent repeat measurement. Patients with a diagnosis of osteoporosis and both pre- and post-treatment measurements of bone mineral density (BMD) and NTX were included. Urinary NTX was measured with the Osteomark enzyme-linked immunosorbent assay. BMD of the hip and lumbar spine was measured using dual energy X-ray absorptiometry (DEXA). RESULTS: A total of 357 patients had serial NTX requests during the time period. Sixty-five of these patients had a diagnosis of osteoporosis. Out of 37 patients treated for osteoporosis who had complete data available, 29 patients had concordant results between BMD and NTX and eight patients had discordant results. Only one patient had treatment changed as a result of a lack of reduction in NTX following treatment. Thirteen patients had therapy altered. Common reasons for altering therapy were patient non-compliance, side effects and failure of BMD to increase. CONCLUSIONS: Alteration to therapy in this patient population is mainly dictated by issues such as patient compliance, medication side effects and bone mineral density results rather than urinary NTX values.

Absorptiometry, Photon↗

Efficacy of B vitamins in lowering homocysteine in older men: maximal effects for those with B12 deficiency and hyperhomocysteinemia.

BACKGROUND AND PURPOSE: A higher plasma concentration of total homocysteine (tHcy) is associated with a greater risk of cardiovascular events. Previous studies, largely in younger individuals, have shown that B vitamins lowered tHcy by substantial amounts and that this effect is greater in people with higher tHcy and lower folate levels. METHODS: We undertook a 2-year, double-blind, placebo-controlled, randomized trial in 299 men aged > or =75 years, comparing treatment with a daily tablet containing 2 mg of folate, 25 mg of B6, and 400 microg of B12 or placebo. The study groups were balanced regarding age (mean+/-SD, 78.9+/-2.8 years), B vitamins, and tHcy at baseline. RESULTS: Among the 13% with B12 deficiency, the difference in mean changes in treatment and control groups for tHcy was 6.74 micromol/L (95% CI, 3.94 to 9.55 micromol/L) compared with 2.88 micromol/L (95% CI, 0.07 to 5.69 micromol/L) for all others. Among the 20% with hyperhomocysteinaemia, the difference between mean changes in treatment and control groups for men with high plasma tHcy compared with the rest of the group was 2.8 micromol/L (95% CI, 0.6 to 4.9 micromol/L). Baseline vitamin B12, serum folate, and tHcy were significantly associated with changes in plasma tHcy at follow-up (r=0.252, r=0.522, and r=-0.903, respectively; P=0.003, <0.001, and <0.001, respectively) in the vitamin group. CONCLUSIONS: The tHcy-lowering effect of B vitamins was maximal in those who had low B12 or high tHcy levels. Community-dwelling older men, who are likely to be deficient in B12 or have hyperhomocysteinemia, may be most likely to benefit from treatment with B vitamins.

Aged↗

Quality assessment of interpretative commenting in clinical chemistry.

BACKGROUND: Clinical interpretation of laboratory results is an integral part of clinical chemistry. However, the performance goals for assessing interpretative commenting in this discipline have not been as well established as for the quality of analytical requirements. METHODS: We present a review of the 10 case reports circulated in the 2002 Patient Report Comments Program by the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists Chemical Pathology Group of RCPA-Quality Assurance Programs Pty Ltd. Participants were expected to add an interpretative comment to a set of results accompanied by brief clinical details. Comments received were broken down into components that were translated into key phrases. An expert panel evaluated the appropriateness of the key phrases and proposed a suggested composite comment. A case summary/rationale was also returned to participants. RESULTS: There was considerable diversity in the range of interpretative comments received for each case report. Although the majority of comments received were felt to be acceptable by the expert panel, some comments were felt to be inappropriate, misleading, or in a few instances, dangerous. CONCLUSION: The golden rule in medicine is "do no harm". Although there is no objective evidence that interpretive comments help to improve patient outcomes, if comments are added to reports it is important that they reflect accepted practice and current guidelines. It is of concern that a large proportion of comments returned were considered to be inappropriate and/or misleading. The Patient Report Comments Program has highlighted the need to consider limiting commenting to persons with clear expertise.

Clinical Chemistry Tests↗

Issues of methodology, standardization and metabolite recognition for 25-hydroxyvitamin D when comparing the DiaSorin radioimmunoassay and the Nichols Advantage automated chemiluminescence protein-binding assay in hip fracture cases.

BACKGROUND: Deficiency of vitamin D is commonly associated with hip fracture and treatment with vitamin D reduces hip fracture rates. Consequently, the demand for assays to measure 25-hydroxyvitamin D (25-OHD) has increased. The Nichols Advantage chemiluminescence protein-binding assay (CLPBA) for 25-OHD is a first-generation automated immunoassay with decreased turnaround time, reduced manual handling and non-radioactive label. METHODS: We compared the CLPBA to the DiaSorin radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC) for the measurement of 25-OHD using 161 samples from hip fracture patients and samples before and after institution of ergocalciferol (vitamin D(2)) therapy. RESULTS: A negative bias for the CLPBA at concentrations below 30 nmol/L and a positive bias at 25-OHD values above 30 nmol/L compared with the RIA resulted in diagnostic discordance for one in three samples when using 30 and 50 nmol/L as decision limits. HPLC analysis confirmed the presence of a negative bias for the CLPBA at low values. Both immunoassays under-estimate 25-hydroxyvitamin D(2). CONCLUSIONS: The discordance between 25-OHD values may be due to differences in standardization of each assay relative to HPLC. Our results emphasize the need for assay-specific clinical decision limits.

Automation↗

A discussion of cases in the 2001 RCPA-AQAP Chemical Pathology Case Report Comments Program.

AIM: We present a descriptive analysis of the 10 case reports distributed in the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists (AACB) Chemical Pathology Patient Report Comments Program to assess the quality of interpretative commenting in clinical biochemistry in 2001. METHOD: Participants were asked to comment on a given set of biochemistry results attached with brief clinical details. All responses received were translated into key phrases and graphically presented on a histogram. An expert panel was asked to evaluate the appropriateness of the key phrases and to propose a suggested composite comment. RESULTS: While the majority of comments received were felt to be acceptable by the expert panel, some comments were felt to be inappropriate or misleading. As comments on laboratory reports may affect clinical management of patients, it is important that these comments reflect accepted practice and current guidelines. CONCLUSION: The Patient Report Comments Program may play an important role in continuing education and possibly in quality assurance of interpretative commenting.

Adult↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Spot urine analysis: acidification does not increase calcium recovery.

INTRODUCTION: We investigated the effects of acidification and storage on calcium recovery in spot urine samples. METHODS: In a retrospective study, 43 spot urine samples from patients with metabolic bone disease, which had been previously analysed fresh for calcium and creatinine, were acidified and incubated for 2 h at room temperature and re-analysed. In a prospective study, fresh spot urine samples from 15 volunteers were split into two aliquots--one left unacidified and the other acidified with 6 mol/L HCl to pH < 2. Both aliquots were analysed immediately and after storage at 4 degrees C for 24 h. RESULTS: In both studies, the calcium creatinine ratios obtained on acidified and non-acidified spot urine samples were not different, both when measured immediately as well as after storage at 4 degrees C for 24 h. CONCLUSIONS: The acidification of spot urine samples would thus appear to be unnecessary for calcium/creatinine measurements in metabolic bone disease if they were undertaken within at least 24 h.

Bone Diseases, Metabolic↗

Cardiovascular disease and osteoporosis: is there a link between lipids and bone?

Atherosclerotic heart disease and osteoporosis are both diseases of old age. Evidence is accumulating for a link between vascular and bone disease. Calcification is a common feature of atherosclerotic plaques, and osteoporosis is associated with both atherosclerosis and vascular calcification. However, the relationship of vascular calcification to the pathogenesis of atherosclerosis remains incompletely understood. Hormone replacement therapy has beneficial effects in the prevention of both atherosclerosis and osteoporosis. Bisphosphonates inhibit bone resorption and are used in the treatment of osteoporosis, whereas the statins inhibit cholesterol biosynthesis and are used for the treatment of atherosclerosis. We have reviewed recent advances in the knowledge of the actions of bisphosphonates and statins at the cellular, molecular and end-organ levels in order to examine the relationship between cardiovascular disease and osteoporosis and to explore the link between lipids and bones. These studies suggest that the mechanism of actions of these two classes of drugs at the cellular level may not be mutually exclusive. There are some early clinical data to complement these findings, suggesting that statins increase bone density and bisphosphonates may have a beneficial effect in vivo on plasma lipid levels and on the atherosclerotic process. Properly designed prospective studies that examine the effect of statins on bone density and fractures, as well as the effects of bisphosphonates on lipid profiles, atherosclerotic progression and cardiovascular morbidity and mortality are needed to define clearly the clinical effects and potential new roles for these agents.

Bone and Bones↗

Decision limit for troponin I and assay performance.

BACKGROUND: The redefinition of acute myocardial infarction by the Joint European Society of Cardiology and American College of Cardiology places troponin at the centre of the diagnostic strategy, in addition to lowering the diagnostic cut-off to the 99th centile of a healthy reference population. The required percentage coefficient of variation (%CV) for the assay at this level is 10. Recent publications have examined the utility of the Bayer ACS:180 troponin I assay at a cut-off of 0.1 microg/L to risk-stratify patients with non-ST-elevation myocardial infarction. METHODS: This study examines the appropriateness of using this assay at this cut-off in individual patients. It also examines the functional sensitivity of the assay and assesses the impact of sample quality on assay performance. RESULTS: At the decision limit of 0.1 microg/L, 8% of patients would be assigned to a different risk group on repeat analysis of the same sample on the ACS:180 due to assay imprecision. The functional sensitivity (at inter-assay %CV = 10) of the ACS:180 troponin I assay was determined to be 0.27 microg/L. Nineteen of 4850 routine samples (0.39%) failed duplicate precision checks as a result of poor sample quality; this was usually due to the presence of small fibrin particles. CONCLUSIONS: Careful attention to sample quality is vital in troponin I measurement. The use of the Bayer assay for risk stratification at a cut-off of 0.1 microg/L can lead to inconsistency of risk assessment in a small but significant proportion of cases.

Autoanalysis↗