Daylily S. Ooi

Bone turnover markers in the management of postmenopausal osteoporosis

Osteoporosis is the most common cause of fragility fractures. Bone remodelling is essential for repairing damaged areas within bone to preserve bone strength and for assisting in mineral homeostases. In young adults, bone remodelling is usually balanced with approximately as much bone replaced as is removed during each remodelling cycle. However, when remodelling becomes accelerated in combination with an imbalance that favours bone resorption over formation, such as during menopause, precipitous losses in bone mass occur. Bone turnover markers (BTMs) measure the rate of bone remodelling allowing for a dynamic assessment of skeletal status and hold promise in identifying those at highest risk of rapid bone loss and subsequent fracture. Further, the use of BTMs to monitor individuals administered osteoporosis therapy is attractive as monitoring anti-fracture efficacy with bone mineral density has significant limitations. This review details remodelling biology, pre-analytical and analytical sources of variability for BTMs, describes the most commonly used resorption and formation markers, and offers some guidelines for their use and interpretation in the laboratory and the clinic.

Efficacy of food fortification on serum 25-hydroxyvitamin D concentrations: systematic review

BACKGROUND Many residents of the United States and Canada depend on dietary sources of vitamin D to help maintain vitamin D status. Because few natural food sources contain vitamin D, fortified foods may be required. OBJECTIVE We aimed to determine the effects of vitamin D-fortified foods on serum 25-hydroxyvitamin D [25(OH)D] concentrations. DESIGN We searched MEDLINE (1966 to June Week 3 2006), Embase, CINAHL, AMED, Biological Abstracts, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) comparing vitamin D-fortified foods with a control and reporting serum 25(OH)D concentrations. Two reviewers independently determined study eligibility, assessed trial quality, and extracted relevant data. Disagreements were resolved by consensus. Meta-analyses of absolute mean change in 25(OH)D were conducted by using a random-effects model, with evaluation of heterogeneity. RESULTS Nine RCTs (n = 889 subjects) were included, of which 8 consistently showed a significant beneficial effect of food fortification on 25(OH)D concentrations. Although 7 RCTs (n = 585 subjects) potentially were meta-analyzable, we were unable to combine the overall results because of significant heterogeneity. The individual treatment effects ranged from 14.5 (95% CIs: 10.6, 18.4) nmol/L to 34.5 (17.64, 51.36) nmol/L (3.4-25 microg vitamin D/d). Subgroup analyses showed a reduction in heterogeneity and significant treatment effect when 4 trials that used milk as the fortified food source were combined. CONCLUSION Most trials were small in size and inadequately reported allocation concealment, but results showed that vitamin D-fortified foods improved vitamin D status in adults.

The Atherogenic Significance of an Elevated Plasma Triglyceride Level

The importance of hypertriglyceridemia as an independent predictor of coronary artery disease (CAD) remains unsettled. Hypertriglyceridemia, with or without associated hypercholesterolemia, occurs more frequently in premature CAD subjects than does hypercholesterolemia alone. With univariate analysis, most studies show a positive correlation between plasma triglyceride (TG) level and risk for CAD, but with multivariate analysis plasma TG level is no longer an independent risk factor except in women and diabetics. Prospective studies have shown that subjects with a high LDL/HDL cholesterol ratio and a high plasma TG level have the highest risk for CAD. Hypertriglyceridemia signifies the presence of excess triglyceride-rich lipoproteins (TRL), including chylomicrons, VLDL, and their remnants. The question then becomes one of whether TRL are directly or indirectly involved in atherogenesis. TRL were thought to be too big to infiltrate the arterial wall, and histopathological studies have shown cholesterol but not triglyceride accumulation in the atherosclerotic plaque. However, there was a recent demonstration of undegraded VLDL and IDL in atherosclerotic plaques. Larger TRL may undergo hydrolysis on the arterial surface to become smaller particles before entry into the intima. Possible cellular pathways for the uptake of TRL by macrophages have been described. The smaller TRL (Sf 20-60), including postprandial chylomicron remnants, are believed to be the most atherogenic of all TRL particles. Because large amounts of TRL are produced in the postprandial period, atherogenesis involving TRL may be primarily a postprandial phenomenon. Once in the intima, TG may undergo hydrolysis, releasing free fatty acids and mono- and diacyl glycerol, accounting for the dearth of TG in atherosclerotic lesions. Particle for particle, VLDL delivers five times as much cholesterol as LDL does to the macrophage.

Effects of contact with vacutainer tube stoppers on the estimation of quinidine in serum and plasma

The effects of blood collection methods on quinidine levels were studied in patients samples and in whole blood with added quinidine. In patient samples, quinidine concentrations were higher in serum than in plasma (p Using heparinized blood samples with added quinidine, plasma drug levels were 29–30% lower in Vacutainer tubes than in all-glass containers. The fall in quinidine occurred principally in the first 5 minutes, and only if whole blood and not just the plasma had been in contact with the stopper. This study shows the contribution that collection methods make to artefactual drug assay results.

Serum human chorionic gonadotrophin levels in early pregnancy

Serum hCG reference intervals for various gestational periods in normal pregnancies were determined using three commercial assays--two standardized against the WHO 2nd IS (Amersham Amerlex-M beta HCG RIA (AMX) and Abbott beta-HCG 15/15 (ABB] and one standardized against the WHO 1 IRP (Hybritech Tandem -E HCG (HYB]. Serial samples from patients with accurately determined gestational periods were analyzed. We correlated these assays to determine the validity of the common practice of interchanging values between assays using the same WHO standard and of converting 1st IRP values to 2nd IS values by a fixed factor. The slope of correlation between the two 2nd IS assays (AMX, ABB) was 1.43, r = 0.960; whereas between the 1 IRP assay (HYB) and the two 2nd IS assays the slopes were 1.67, r = 0.963 and 1.22, r = 0.971 for AMX and ABB, respectively. In a prospective study of 52 patients with normal pregnancies, serum beta-hCG values in 46% of samples taken at 28-35 days gestation fell below the lower limit of the reference curves supplied with the AMX kit. Ninety-two percent of samples were within the newly established intervals. These results indicate that suppliers reference limits may not be accurate; in addition, a common factor should not be used to convert values from one commercial kit to another.

The value of urinary chloride measurement in distinguishing surreptitious vomiting from Bartter's syndrome

Urinary chloride measurement is a simple and common procedure but its value in clinical practice is not extensive. This case report highlights a practical and important use of this test. A patient presented with most of the clinical and metabolic derangements of Bartters syndrome but was found to have extremely low or absent urinary chloride excretion. Her ability to excrete chloride was, however, intact during a chloride load test. The finding of low urinary chloride excretion did not support the diagnosis of Bartters syndrome and suggested an extrarenal loss of chloride. This was confirmed when she eventually admitted to surreptitious vomiting.

Serum CK-MB activity during and after aortocoronary bypass surgery

Frequent serum sampling of CK-MB and total CK levels was carried out in 100 patients during and up to 48 hours following aortocoronary bypass surgery. Using an ion exchange chromatography method for CK-MB determination, significantly higher serum CK-MB levels (peak 46.1 +/- 5.2 cf. 31.3 +/- 2.2 u/L), but not total CK levels were present 6 to 16 hours postoperatively in those with new Q waves in the ECG. Serum levels of CK-MB in those patients with uncomplicated surgery were defined. New post-operative Q waves were seen in only one half of cases with frankly abnormal CK-MB curves and seriously underestimated the incidence of perioperative infarction. Peak levels of CK-MB in patients with new Q waves occurred within 16 hours of surgery suggesting that infarction is usually an intraoperative or early post-operative event.