Burritt, Mary F.

Summary Intact Fcα fragments from five human IgA myeloma proteins were produced by two different methods, high temperature trypsinolysis and IgA protease digestion. Three of the Fcα fragments activated the classical pathway as determined by the titers of the individual complement components. Two other fragments did not fix complement by either pathway.

Abstract In recent years, laboratory testing in the critical-care setting has increased, a trend due, in part, to the evolution of electrochemical sensors. Various innovations have extended sensor lifetimes, reduced sensor maintenance, and led to the development of single-use and unit-use disposable sensors. These sensor technologies allow the accurate and precise determination, either at or near the bedside, of several analytes including pO2, pCO2, pH, Na, K, Cl, ionized calcium, hematocrit, total hemoglobin, and glucose. Use of these new systems, however, has raised new issues regarding sensor calibration and sample handling and collection. The number of direct-reading analyzers for electrolyte determinations has also increased dramatically. Issues regarding calibration of ion-selective electrodes (ISEs) for Na/K have also been raised after demonstrations of between-instrument variation. Recently, collaborative efforts between eight ISE instrument manufacturers and the National Institute of Standards and Technology resulted in the development of a Standard Reference Material, SRM 956, for the purpose of standardizing direct-reading Na/K ISEs to the flame photometer. Other widely used technologies that provide noninvasive, continuous monitoring include pulse oximetry and transcutaneous gas electrodes. These trends are expected to continue and to produce a new generation of electrochemical and optical sensors.

1. To investigate whether there is a nyctohemeral rhythm in bone turnover, we measured serum bone Gla-protein (osteocalcin, an index of osteoblast activity) concentration every 2 h and urinary deoxypyridinoline (a marker of bone collagen resorption) excretion for 8 h periods in 10 pubertal girls (aged 10–14 years), 15 premenopausal women (aged 20–49 years) and 17 postmenopausal women (aged 50–75 years). 2. The serum concentration of bone Gla-protein and the urinary excretion of deoxypyridinoline were five times higher in the pubertal girls than in the premenopausal women. The urinary excretion of deoxypyridinoline in the postmenopausal women was twice that in the premenopausal women. 3. There was a nyctohemeral pattern in all age groups with mean night-time increases of 28% (P<0.001) in the urinary excretion of deoxypyridinoline and of 5% (P<0.001) in the serum bone Gla-protein concentration. 4. There also were nyctohemeral patterns in the urinary excretion of calcium (P<0.02), sodium (P<0.001) and potassium (P<0.001), with decreases at night. There was a negative correlation between the night-time changes in the urinary excretion of deoxypyridinoline and calcium, especially in adult women (P<0.01). 5. The serum level of parathyroid hormone increased with age, but this effect was only observed at night (01.00 to 07.00 hours). There was a nyctohemeral rhythm of the serum intact parathyroid hormone level at all ages, with a peak in the afternoon and night. 6. Thus, at night, there is a large increase in bone resorption and a small increase in osteoblastic activity, representing a nyctohemeral rhythm of bone turnover. Although the amplitudes of bone formation and bone resorption are greater during growth, the pattern of nyctohemeral changes present during growth continues up to the age of 75 years.

Bone turnover has a circadian pattern, with bone resorption and, to a lesser extent, bone formation increasing at night. Serum cortisol also has a circadian pattern and is a potential candidate for mediating the circadian changes in bone turnover. Thus, we measured bone formation and resorption markers before (study A) and after (study B) elimination of the morning peak of cortisol. We also assessed effects of the circadian cortisol pattern on serum calcium, PTH, and urinary calcium excretion. Ten normal postmenopausal women, aged 63–75 yr (mean, 69 yr), were studied. Metyrapone was administered to block endogenous cortisol synthesis and either a variable (study A) or a constant (study B) infusion of cortisol was given to reproduce and then abolish the morning cortisol peak. Blood was sampled every 2 h for serum cortisol, ionized calcium, PTH, and bone formation markers[ osteocalcin and carboxyl-terminal propeptide of type I collagen (PICP)], and timed 4-h urine samples were collected for measurement of calcium, phosphorus, sodium, potassium, and bone resorption markers (N-telopeptide of type I collagen and free deoxypyridinoline).During study A, serum osteocalcin had a circadian pattern, with a peak at 0400 h and a nadir at 1400 h. During study B, however, the afternoon nadir of serum osteocalcin was eliminated (P < 0.001 and P < 0.005 for the difference in the patterns of peak and nadir, respectively, on the 2 study days). In contrast, the circadian patterns of serum PICP and urinary N-telopeptide of type I collagen and free deoxypyridinoline were virtually identical during the two studies. Urinary calcium excretion declined after the cortisol peak, without differences between the 2 study days in phosphorus or sodium excretion or in serum PTH. We conclude that the circadian variation in serum cortisol is responsible for the circadian pattern of serum osteocalcin, but not that of PICP or bone resorption markers. The physiological variation in serum cortisol may also reduce urinary calcium excretion.

Abstract Whether hemoglobin A1c (HbA1c) values are suitable for diagnosing diabetes has been debated. We sought to assess the prevalence of elevated HbA1c levels in a prediabetes patient population. Oral glucose tolerance tests and HbA1c levels were analyzed for patients entering a diabetes prevention program between January 1, 2007, and September 13, 2009. We calculated the percentage of patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) who had HbA1c values in the 6.0% to 6.4% range or in the 5.7% to 6.4% range. The mean age of the 242 patients was 62 years; 64.0% were women, and 88.0% were white. Isolated IFG was detected in about 56.2% of patients and combined IFG and IGT in about 37.2%. Only 28.5% of patients had HbA1c values in the 6.0% to 6.4% range, whereas 65.3% had values in the 5.7% to 6.4% range. Our data suggest that reliance on HbA1c testing alone to identify candidates for a diabetes prevention program would miss a substantial number of eligible patients.