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Biomedical subjects

J A Shepherd

Publications and source records attributed to J A Shepherd.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of BMD precision for Prodigy and Delphi spine and femur scans.

INTRODUCTION: Precision error in bone mineral density (BMD) measurement can be affected by patient positioning, variations in scan analysis, automation of software, and both short- and long-term fluctuations of the densitometry equipment. Minimization and characterization of these errors is essential for reliable assessment of BMD change over time. METHODS: We compared the short-term precision error of two dual-energy X-ray absorptiometry (DXA) devices: the Lunar Prodigy (GE Healthcare) and the Delphi (Hologic). Both are fan-beam DXA devices predominantly used to measure BMD of the spine and proximal femur. In this study, 87 women (mean age 61.6+/-8.9 years) were measured in duplicate, with repositioning, on both systems, at one of three clinical centers. The technologists were International Society for Clinical Densitometry (ISCD) certified and followed manufacturer-recommended procedures. All scans were acquired using 30-s scan modes. Precision error was calculated as the root-mean-square standard deviation (RMS-SD) and coefficient of variation (RMS-%CV) for the repeated measurements. Right and left femora were evaluated individually and as a combined dual femur precision. Precision error of Prodigy and Delphi measurements at each measurement region was compared using an F test to determine significance of any observed differences. RESULTS: While precision errors for both systems were low, Prodigy precision errors were significantly lower than Delphi at L1-L4 spine (1.0% vs 1.2%), total femur (0.9% vs 1.3%), femoral neck (1.5% vs 1.9%), and dual total femur (0.6% vs 0.9%). Dual femur modes decreased precision errors by approximately 25% compared with single femur results. CONCLUSIONS: This study suggests that short-term BMD precision errors are skeletal-site and manufacturer specific. In clinical practice, precision should be considered when determining: (a) the minimum time interval between baseline and follow-up scans and (b) whether a statistically significant change in the patient's BMD has occurred.

Absorptiometry, Photon↗
PubMed2005

Metacarpal index and bone mineral density in healthy African-American women.

Bone mineral density (BMD) reference data of non-Caucasian women is scarce but greatly needed for African-American women. The objective of this study was to establish a metacarpal normative reference database for African-American women using digital X-ray radiogrammetry (DXR) and hand radiographs and compare these values to existing Caucasian data. Two hundred and fifty healthy African-American women between the ages of 20 and 79 years old, 14 of whom were excluded, were recruited to participate from four different clinical sites. The study population was recruited in approximately equal number into the following groups: 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years of age. A radiograph was acquired of each subject's non-dominant hand. The radiographs were scanned and analyzed using radiogrammetric techniques, and the BMD, MCI (Metacarpal Index), bone width and cortical thickness were calculated. The regression curve that best fit the data was a second order polynomial. The BMD and MCI of young adult women (20-40 years of age) were used to calculate T-score parameters. The young reference BMD and MCI with their associated standard deviations were found to be 0.6045 g/cm2+/-0.0529 g/cm2 and 0.5096 and 0.0792, respectively. However, the MCI was found to be approximately 2.5% lower (-0.0118) compared to Caucasian women. The African-American metacarpal BMD was found to be 3.5% (0.0207 g/cm2) higher across all ages when compared to existing Caucasian reference data acquired in a similar way. The differences were found to be entirely due to larger bone size, cortical diameter and bone width in the African-American women.

Absorptiometry, Photon↗
PubMed2005

Towards standardization of dual X-ray absorptiometry (DXA) at the forearm: a common region of interest (ROI) improves the comparability among DXA devices.

Manufacturer-implemented regions of interest (ROIs) to determine the bone mineral density (BMD) at the forearm are currently not standardized across dual X-ray absorptiometry (DXA) devices. We hypothesized that their differences introduce considerable variation in measurement results for forearm BMD when taken on different devices, and that a ROIs common to all devices with standardized placement and size significantly improve device comparability. The common ROI was defined to have a fixed length of 2 cm and to extend proximally from the location where the ulna and radius bones superimpose on the DXA image. The effects of universal standardization of forearm BMD were combined with and compared to those of the common ROI. They were drawn on 91 female study participants (ages 20-80 years, 10 per decade) who were scanned on Hologic QDR-4500, Aloka DCS-600EX, GE Lunar PIXI and Norland pDEXA DXA scanners. For all device combinations, manufacturer-implemented ROI root mean-square errors were significantly higher than for the common ROI, suggesting that implementing an ROI with common design on all scanners is a good way to reduce interdevice variability. When manufacturer-implemented ROIs were universally standardized root mean-square error (RMSE) values were less different from that of the nonstandardized Common ROI, suggesting that universal standardization can further improve interdevice comparability even when a common ROI such as the one implemented here is used. ROI standardization dramatically improves interdevice comparability.

Absorptiometry, Photon↗
PubMed2002

Does osteoporosis classification using heel BMD agree across manufacturers?

The lack of standardization in bone mineral density (BMD) measurements is known. Several studies have been carried out to cross-calibrate the axial dual X-ray absorptiometry (DXA) devices. Recently, a number of peripheral DXA (pDXA) densitometers have been introduced. In this study we evaluated the agreement between two heel DXA devices on BMD and T-scores. A total of 99 females aged 21-78 years (ca. 16 per decade) had their non-dominant heel BMD measured using the PIXI (Lunar Inc.) and the Apollo (Norland Medical) pDXA scanners. The mean BMD values were 0.492 and 0.607 g/cm(2) and the mean T-scores using manufacturers' specified reference data were -0.07 and -0.25 for the PIXI and Apollo, respectively. Both the BMD and T-score intermachine relationships were highly correlated but showed significant nonidentity slopes and non-zero offsets. The diagnostic comparison on T-scores resulted in 86% agreement between the instruments (weighted kappa score of 0.550). Normalizing the reference peaks and SDs using this study's young adult population BMD results removed the systematic T-score disagreement. We found that PIXI and Apollo are highly correlated. Differences in BMD values are mainly due to different region of interest (ROI) definitions and additional T-score disagreement reflects the difference in normative databases.

Absorptiometry, Photon↗
PubMed2001

Evaluation of a gel-coupled quantitative ultrasound device for bone status assessment.

OBJECTIVE: To evaluate a new gel-coupled calcaneal quantitative ultrasound system, Osteospace (Medilink, Montpellier, France), which was designed to assess the status of bone in the calcaneus. METHODS: The study group consisted of 215 healthy white women aged 20 to 85 years and 51 white women aged 60 to 86 years with osteoporotic fractures. Fifty-two healthy women aged 50 to 85 years were randomly selected from the healthy cohort as the control group. All the women had calcaneal quantitative ultrasonic measurements. The women with osteoporotic fractures and the control group also had proximal femur and lumbar anteroposterior spine bone mineral density measurements using dual X-ray absorptiometry. Bone mineral density was also measured in a subgroup of 54 women at the calcaneus. RESULTS: There was a significant inverse correlation of broadband ultrasound attenuation and speed of sound with age (P < .001). Short-term measurement precision values expressed as coefficients of variation were 1.72% for broadband ultrasound attenuation and 0.64% for speed of sound, and standardized short-term precision values were 6.09% for broadband ultrasound attenuation and 3.87% for speed of sound. The correlations between the quantitative ultrasonic parameters and calcaneal bone mineral density were 0.69 (P = .0001) for broadband ultrasound attenuation and 0.45 (P = .0008) for speed of sound. Both quantitative ultrasonic parameters and all bone mineral density measurements of the hip and spine differed significantly between the control and osteoporotic fracture groups (P < .01). Age-, weight-, and height-adjusted odds ratios per SD decrease were as follows: broadband ultrasound attenuation, 1.79; speed of sound, 1.83; spine bone mineral density, 2.34; femoral neck bone mineral density, 1.69; and total hip bone mineral density, 1.85. The areas under the receiver operating characteristic curve for quantitative ultrasound parameters and bone mineral density measurements were close, ranging from 0.75 to 0.80. CONCLUSIONS: This new quantitative ultrasound system can detect age- and menopause-related influences on skeletal status and can discriminate healthy women from those with osteoporotic fractures in a manner comparable with that of bone mineral density measurement by dual X-ray absorptiometry.

Adult↗
PubMed2000

Vertebral fractures in osteoporosis: a new method for clinical assessment.

Vertebral fractures are the most common consequence of osteoporosis, and are an important risk factor for subsequent fractures. Patients with reduced bone mineral density (BMD) and vertebral fractures have significantly increased risk for future fractures, indicating great potential for the combined use of fracture assessment and BMD in risk evaluation. Despite the established importance of fractures, however, vertebral assessment is not typically performed in the clinical evaluation of patients at risk for osteoporosis. Radiographs are the accepted standard for assessment of fractures, but are rarely obtained in osteoporosis assessment for a variety of practical reasons, including cost, radiation dose, and the lack of office-based radiological facilities. Clinical assessment of fractures is difficult because most are asymptomatic. Consequently, this strong risk factor for osteoporotic fractures is often overlooked. High-resolution lateral spine images, obtained on advanced fan-beam dual X-ray absorptiometry (DXA) systems, provide a practical, low-radiation dose, point-of-care methodology for assessment of vertebral fractures, and have the potential to address this important clinical need. In this article, we review the importance of vertebral fractures and the methods of assessing them. We also review clinical data supporting the feasibility of visual evaluation of lateral spine images obtained using a fan-beam DXA system, and discuss the potential positive impact of this new methodology on clinical patient evaluation.

Absorptiometry, Photon↗
PubMed1997

Characterization of the COQ5 gene from Saccharomyces cerevisiae. Evidence for a C-methyltransferase in ubiquinone biosynthesis.

Ubiquinone (coenzyme Q or Q) is a lipophilic metabolite that functions in the electron transport chain in the plasma membrane of prokaryotes and in the inner mitochondrial membrane of eukaryotes. Q-deficient mutants of Saccharomyces cerevisiae fall into eight complementation groups (coq1-coq8). Yeast mutants from the coq5 complementation group lack Q and as a result are respiration-defective and fail to grow on nonfermentable carbon sources. A nuclear gene, designated COQ5 was isolated from a yeast genomic library based on its ability to restore growth of a representative coq5 mutant on media containing glycerol as the sole carbon source. The DNA segment responsible for the complementation contained an open reading frame (GenBankTM accession number Z49210Z49210) with 44% sequence identity over 262 amino acids to UbiE, which is required for a C-methyltransferase step in the Q and menaquinone biosynthetic pathways in Escherichia coli. Both the ubiE and COQ5 coding sequences contain sequence motifs common to a wide variety of S-adenosyl-L-methionine-dependent methyltransferases. A gene fusion expressing a biotinylated form of Coq5p retains function, as assayed by the complementation of the coq5 mutant. This Coq5-biotinylated fusion protein is located in mitochondria. The synthesis of two farnesylated analogs of intermediates in the ubiquinone biosynthetic pathway is reported. These reagents have been used to develop in vitro C-methylation assays with isolated yeast mitochondria. These studies show that Coq5p is required for the C-methyltransferase step that converts 2-methoxy-6-polyprenyl-1, 4-benzoquinone to 2-methoxy-5-methyl-6-polyprenyl-1,4-benzoquinone.

Amino Acid Sequence↗
PubMed1996

Complementation of coq3 mutant yeast by mitochondrial targeting of the Escherichia coli UbiG polypeptide: evidence that UbiG catalyzes both O-methylation steps in ubiquinone biosynthesis.

Ubiquinone functions in the mitochondrial electron transport chain. Recent evidence suggests that the reduced form of ubiquinone (ubiquinol) may also function as a lipid soluble antioxidant. The biosynthesis of ubiquinone requires two O-methylation steps. In eukaryotes, the first O-methylation step is carried out by the Coq3 polypeptide, which catalyzes the transfer of a methyl group from S-adenosylmethionine to 3,4-dihydroxy-5-polyprenylbenzoate. In Escherichia coli, 2-polyprenyl-6-hydroxyphenol is the predicted substrate; however, the corresponding O-methyltransferase has not been identified. The second O-methylation step in E. coli, the conversion of demethylubiquinone to ubiquinone, is carried out by the UbiG methyltransferase, which is 40% identical in amino acid sequence with the yeast Coq3 methyltransferase. On the basis of the chemical similarity of the first and last methyl-acceptor substrates and the high degree of amino acid sequence identity between Coq3p and UbiG, the ability of UbiG to catalyze both O-methylation steps was investigated. The current study shows that the ubiG gene is able to restore respiration in the yeast coq3 mutant, provided ubiG is modified to contain a mitochondrial leader sequence. The mitochondrial targeting of O-methyltransferase activity is an essential feature of the ability to restore respiration and hence ubiquinone biosynthesis in vivo. In vitro import assays show the mitochondrial leader sequence present on Coq3p functions to direct mitochondrial import of Coq3p in vitro and that processing to the mature form requires a membrane potential. In vitro methyltransferase assays with E. coli cell lysates and synthetically prepared farnesylated-substrate analogs indicate that UbiG methylates both the derivative of the eukaryotic intermediate, 3,4-dihydroxy-5-farnesylbenzoate, as well as that of the E. coli intermediate, 2-farnesyl-6-hydroxyphenol. The data presented indicate that the yeast Coq3 polypeptide is located in the mitochondria and that E. coli UbiG catalyzes both O-methylation steps in E. coli.

Base Sequence↗
PubMed1988

Antibacterial action of 2-bromo-2-nitropropane-1,3-diol (bronopol).

Patterns of growth inhibition of Escherichia coli in the presence of 2-bromo-2-nitropropane-1,3-diol (bronopol) indicate a period of biocide-induced bacteriostasis followed by growth at an inhibited rate. The length of the bacteriostatic period, but not the subsequent growth inhibition, was reduced by the addition of excess cysteine. Patterns of growth inhibition were unaffected by catalase or superoxide dismutase. The bactericidal concentrations (100 to 500 micrograms/ml) were considerably in excess of the MIC (13 micrograms/ml) and generally produced first-order reductions in viability. Bactericidal activity was considerably reduced by anoxic conditions and by the presence of catalase or superoxide dismutase. Results indicate that there are two distinct reactions between bronopol and thiols. Under aerobic conditions, bronopol catalytically oxidizes thiol-containing materials such as cysteine, with atmospheric oxygen as the final oxidant. By-products of this reaction are active oxygen species such as superoxide and peroxide, which are directly responsible for the bactericidal activity of the compound and for the reduced growth rate after the bacteriostatic period. The latter effect probably results from the oxidation of intracellular thiols such as glutathione and cysteine. Catalytic oxidation of thiols in the presence of excess thiol leads to the creation of an anoxic state. Under these conditions, the slower reaction with thiols, which consumes bronopol, predominates. Consumption of bronopol by its reaction with thiols, without the involvement of oxygen, leads to the eventual removal of bronopol from treated suspensions and the resumption of growth.

Anti-Bacterial Agents↗
PubMed1976

Inhibition of prostaglandin E2 secretion. Failure to abolish autoregulation in the isolated dog kidney.

We studied the role of renal prostaglandins in the regulation of glomerular filtration rate (GFR) and renal blood flow (RBF) in the isolated dog kidney. Indomethacin or meclofenamate, 2 mg/kg of body weight, suppressed renal prostaglandin E2 (PGE2) secretion, measured by radioimmunoassay, to zero within 20 minutes; the effect persisted for the duration of the study. When renal arterial pressure (PRA) was maintained at 104 mm Hg both drugs caused a sharp decrease in sodium excretion and RBF with redistribution of flow from inner to outer cortes we examined autoregulation of GFR and RBF over the pressure ranges of 150-100 and 150-75 mm Hg, respectively, after inhibition of PGE2 secretion and under control conditions. deltaGFR/deltaPRA (ml/min per mm Hg) was 0.020 +/- 0.017 in the indomethacin group, 0.152 +/- 0.055 in the meclofenamate group, and 0.086 +/- 0.017 in the control group. The change in GFR for the indomethacin group was significantly less than that for meclofenamate (P less than 0.01) and control groups (P less than 0.025); the latter two groups were not statistically different from each other (P greater than 0.1). There was no significant difference (P greater than 0.1) between the three groups with respect to deltaRBF/deltaPRA, which measured 0.288 +/- 0.046, 0.370 +/- 0.112, and 0.438 +/- 0.123 ml/min per mm Hg in the indomethacin, meclofenamate and control groups, respectively. Renal was lowered from 150 to 75 mm Hg. The observation that inhibition of prostaglandin synthesis promotes a redistribution of RBF from inner to outer cortex suggests that renal prostaglandins may participate in the regulation of medullary blood flow. However, since autoregulation of GFR and RBF remained intact despite inhibition of prostaglandin secretion, these data argue against a role for renal prostaglandins in regulating whole kidney GFR and RBF.

Animals↗