A Comparison of Antiserum and Protein A as Secondary Reagents to Assess Toxoplasma gondii Antibody Titers in Cats and Spotted Hyenas.

Toxoplasma gondii is a protozoal parasite with worldwide distribution that is able to infect a wide variety of mammals and birds. Our main goal was to screen for T. gondii antibody titers in a previously untested species, the spotted hyena ( Crocuta crocuta); however, this goal first required us to investigate serological procedures that could be suitable for hyenas. Cats are the closest domestic relations of hyenas, so T. gondii antibody titers were first compared in 26 feral cats with specific or nonspecific fluorophore-labeled secondary reagents, i.e., anti-cat IgG or protein A. Substitution of anti-cat IgG with protein A caused a statistically significant drop in titer measurements in cats (P = 0.01) with a reduction of the geometric mean titer equivalent to 1 doubling-dilution. The same procedures were then applied to captive spotted hyenas. Titers measured in 9 of 10 hyenas were identical whether anti-cat IgG or protein A was used as the secondary reagent: 5 had titers <1:16, 2 had titers of 1:16, and 2 had titers of 1:32. One hyena had maximum titers of 1:64 or 1:32 when anti-cat IgG or protein A was used, respectively. The use of protein A as the secondary reagent in serologic assays can be applied to a range of mammalian species and seems unlikely to affect test specificity; however, the use of protein A may reduce test sensitivity, as suggested in the present study using cats. Despite a control program, some exposure to T. gondii had occurred in the Zoo's spotted hyenas.

Randomized placebo-controlled trial of long-term treatment with sibutramine in mild to moderate obesity.

OBJECTIVE: The researchers assessed the long-term weight reduction efficacy, tolerability, and safety of sibutramine used once daily in conjunction with behavior modification to treat mild to moderate obesity. STUDY DESIGN: This was a double-blind randomized placebo-controlled parallel-group comparative study of sibutramine 10 mg or 15 mg (or placebo) once daily for 1 year, given with dietary advice. POPULATION: A total of 485 obese men and women with uncomplicated obesity were included (mean age=42 years, mean body mass index=32.7 kg/m2). OUTCOMES MEASURED: The outcomes were mean weight loss, percentage losing more than 5% or 10% of their body weight, and adverse drug effects. RESULTS: Among patients completing the study, those taking sibutramine 10 mg or 15 mg had greater mean weight loss compared with placebo at 12-month assessment (P < or = .001). Changes in body weight from baseline to end point were -1.6 kg for those taking placebo, -4.4 kg for those taking sibutramine 10 mg (P < or =.01, last observation carried forward [LOCF]), and -6.4 kg for those taking sibutramine 15 mg (P < or =.001, LOCF). For placebo patients, 20% lost 5% or more of their body weight compared with 39% of patients taking sibutramine 10 mg and 57% taking sibutramine 15 mg. Only 7% of the patients taking placebo lost 10% or more of their body weight, compared with 19% taking sibutramine 10 mg and 34% taking sibutramine 15 mg (P <.001 for both 10 mg and 15 mg vs placebo, and for both > or =5% and > or =10%). CONCLUSIONS: Sibutramine 10 mg or 15 mg once daily given with dietary advice produces and maintains statistically and clinically significantly greater weight loss than dietary advice alone (placebo) throughout a 12-month treatment period, and is safe and well tolerated.

Vertebral morphometry: a comparison of long-term precision of morphometric X-ray absorptiometry and morphometric radiography in normal and osteoporotic subjects.

Vertebral morphometry, the quantification of vertebral body shape, has proved a useful tool in the identification and evaluation of osteoporotic vertebral deformities in both epidemiologic surveys and clinical trials. Although conventionally it has been performed on lateral radiographs of the thoracolumbar spine (morphometric radiography, MRX), it may now be accomplished on morphometric X-ray absorptiometry (MXA) scans, acquired on dual-energy X-ray absorptiometry (DXA) machines. In this study the long-term precision of vertebral height measurement using MXA and MRX was directly compared. Initially 24 postmenopausal women were recruited (mean age 67+/-5.8 years): 12 normal subjects (group 1) and 12 with osteoporosis and known vertebral deformities (group 2). Each subject attended for a baseline visit at which they had a MXA examination and lateral thoracic and lumbar radiographs. Twenty-one subjects then returned 1.7+/-0.4 years later (10 subjects from group 1 and 11 from group 2) for a follow-up visit to repeat both the MXA scans and conventional radiographs. The baseline MXA scans and conventional radiographs were each analyzed quantitatively by two observers in a masked fashion, using a standard six-point method. The follow-up images were then analyzed by the same observers. The MRX observers were masked to the baseline analyses, while the MXA observers utilized the manufacturer's 'compare' facility. On all scans and radiographs anterior (Ha), mid (Hm) and posterior (Hp) vertebral heights were measured and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios calculated for each vertebral body, ideally from T4 to L4. MRX analyzed 129 of the 130 available vertebrae in group 1 at both visits and 141 of the 143 available in group 2, while MXA analyzed 124 vertebrae in group 1 at both visits and 127 in group 2. Intra- and inter-observer precision errors, particularly in terms of coefficient of variation (CV%), were larger for MXA than for MRX in both normal subjects and those with vertebral deformities. For example, intra-observer precision errors for vertebral height measurement were 0.62 mm (2.9%) for MXA compared with 0.63 mm (2.2%) for MRX in group 1 (normal) subjects and 0.82 mm (4.2%) for MXA compared with 0.85 mm (3.3%) for MRX for group 2 (osteoporosis and vertebral deformities) subjects. Both MXA and MRX inter-observer precision was clearly poorer than the intra-observer precision, a problem associated with any morphometric technique. This was particularly noticeable for MXA; for example, precision of vertebral height measurement in group 1 subjects was 0.62 mm (2.9%) for intra-observer compared with 0.99 mm (4.6%) for inter-observer analyses. MXA and MRX intra- and inter-observer precision was significantly poorer for subjects with vertebral deformities compared with those without, with the CV% for subjects with vertebral deformity approximately 50% greater than that of normal subjects. For example, MRX intra-observer precision for the midwedge ratio was 2.6% for group 1 subjects compared with 3.8% for group 2 subjects. The precision of vertebral height measurement on deformed vertebrae of group 2 subjects was poorer than that for normal vertebrae in the same subjects using both MXA and MRX, as a result of increased variability in point placement. For example, MXA intra-observer precision (RMS SD) for the wedge ratio precision was 0.037 (3.9%) for normal vertebrae compared with 0.060 (6.6%) for deformed vertebrae. We conclude that MXA precision was generally poorer than MRX, although both techniques were adversely affected by the presence of vertebral deformities and the use of more than one observer. Although precision errors for both techniques were substantially smaller than the 20-25% reduction in vertebral height frequently proposed to identify incident deformities, the poorer precision of MXA may lead to an increased risk of erroneous classification of vertebrae as normal or deformed.

Is a calculated total hip BMD of clinical use?

The diagnosis of osteoporosis is based on bone mass measurement. To avoid the errors associated with the measurement of spinal bone density the total hip has been accepted as the standard measurement site. This information is not available for many early measurements. We have assessed whether it is possible to derive clinically useful information about total hip bone mineral density (BMD) from measurements at other hip sites. The bone mass measurements of 46 patients participating in a current trial of therapy for osteoporosis were reviewed. The total hip BMD as directly measured was compared with that obtained from the formula: Total hip BMD = 0.48 x Neck BMD + 0.62 x Trochanteric BMD + 0.03. In 30 patients with follow-up data the rate of change in hip BMD over a year was also determined by both methods. In the pretreatment state there was good agreement between the two measures (r2 = 0.96, SEE 0.012 g/cm2). If the formula was used to compute a change in total hip BMD, the agreement between both methods remained good. However, the standard error of the estimate of the change represented 59% of the observed change. This indicates that the error associated with this estimate is too great to allow clinically meaningful conclusions to be drawn from calculated total hip BMD. We conclude that, whilst it may be possible to obtain reasonable point estimates of total hip BMD from other measures in the hip, these estimates are too imprecise to allow conclusions about change in BMD to be made.

Morphometric X-ray absorptiometry and morphometric radiography of the spine: a comparison of analysis precision in normal and osteoporotic subjects.

Morphometric techniques, which use conventional lateral spine radiographs to quantify vertebral body shape (morphometric radiography, MRX), have proved a useful tool in the identification and evaluation of osteoporotic vertebral deformities. Recently a new method of acquiring the images required for vertebral morphometry using dual-energy X-ray absorptiometry scanners (morphometric X-ray absorptiometry, MXA) has been developed. In this study we compare repeat analysis precision of vertebral height measurement using MXA and MRX. Twenty-four postmenopausal women were recruited (mean age 67 +/- 5.8 years): 12 normal subjects and 12 with osteoporosis and vertebral deformities. Each subject had a MXA scan and lateral thoracic and lumbar radiographs at a single appointment, which were each analyzed quantitatively in a masked fashion, using a standard 6-point method, twice by one observer and once by a second observer. Anterior (Ha), mid (Hm) and posterior (Hp) vertebral heights were measured and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios calculated for each vertebral body. Intra- and interobserver precision were consistently poorer in MXA compared with MRX in both normal subjects and those with vertebral deformities, with MXA CV% generally at least 50% higher than corresponding values for MRX. For both MXA and MRX interobserver precision was clearly poorer than intraobserver precision, a problem associated with any morphometric technique. MXA intra- and interobserver precision were significantly poorer for subjects with vertebral deformities compared with those without, with a CV% for deformity subjects up to twice that of normal subjects. Conversely, MRX showed little or no obvious worsening of intra- or interobserver precision for deformity subjects. Comparison of MXA precision in the normal and deformed vertebrae of the deformity subjects demonstrated that the poorer precision in these subjects compared with normal subjects was the result of increased variability in point placement on the deformed vertebrae themselves. However, the precision for normal vertebrae in these subjects was also somewhat poorer than the precision in normal subjects. We conclude that MXA precision is generally poorer than that of MRX and that the presence of vertebral deformities has a more pronounced effect on MXA precision than on MRX precision.

Morphometric X-ray absorptiometry: reference data for vertebral dimensions.

Vertebral fractures are a common and important consequence of osteoporosis and are often identified via morphometric analysis of conventional lateral spine radiographs (morphometric radiography or MRX). A new method of performing vertebral morphometry using images acquired on dual-energy X-ray absorptiometry (DXA) scanners (morphometric X-ray absorptiometry or MXA) has recently been developed. In this study, we derive reference data for vertebral heights and height ratios using MXA scans as the data source and compare the results with previously published MRX studies. One thousand and nineteen Caucasian women (mean age 63 years, range 33-86) were recruited. An MXA scan, covering 13 vertebrae from L4 to T4, was acquired for each subject on one of four DXA systems located at three centers in the U.K. Analysis of variance found statistically significant but relatively small differences among centers, machines, and scan modes, and therefore data were pooled for reference range calculations. Three vertebral heights (anterior, mid, and posterior) were measured and four ratios (wedge, mid-wedge, and two crush) calculated. These data sets were trimmed using an iterative algorithm to remove extreme values assumed to represent deformed vertebrae, then mean and SD values were calculated using the remaining data. When the data were split by age, a small but statistically significant decrease in vertebral height between the sixth and eighth decades was found, but this was not replicated for the vertebral height ratios. Marked differences were observed between MXA data and MRX, but were comparable to those between different MRX studies. These may result from differences in image quality and point placement protocols, population differences, differences in radiographic technique, and differences in the derivation of a group of "normal" vertebrae. This study suggests that reference data of vertebral dimensions should be specific to the technique which uses those data as a reference, i.e., MXA.