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Biomedical subjects

M Melton

Publications and source records attributed to M Melton.

5 recordsLinked to original sources

Development and validation of a simple questionnaire to facilitate identification of women likely to have low bone density.

The relationship between low bone mass and risk of fracture is well documented. Although bone densitometry is the method of choice for detecting low bone mass, its use may be limited by the availability of equipment, cost, and reimbursement issues. Improved patient selection for bone densitometry might increase the cost-effectiveness of screening for osteoporosis, a goal we sought to achieve by developing and validating a questionnaire based solely on patient-derived data. Responses to the questionnaire were used to assign postmenopausal women to one of two groups: (1) those unlikely to have low bone mineral density (defined as 2 standard deviations or more below the mean bone mass at the femoral neck in young, healthy white women) and therefore probably not currently candidates for bone densitometry; and (2) those likely to have low bone mineral density and therefore probably candidates for bone densitometry. We asked community-dwelling perimenopausal and postmenopausal women attending one of 106 participating multispecialty centers (both academic and community based) to complete a self-administered questionnaire and undergo bone density measurement using dual x-ray absorptiometry. We used regression modeling to identify factors most predictive of low bone density at the femoral neck in the postmenopausal group. A simple additive scoring system was developed based on the regression model. Results were validated in a separate cohort of postmenopausal women. Data were collected from 1279 postmenopausal women in the development cohort. Using only six questions (age, weight, race, fracture history, rheumatoid arthritis history, and estrogen use), we achieved a target of 89% sensitivity and 50% specificity. The likelihood ratio was 1.78. Validation in a separate group of 207 postmenopausal women yielded 91% sensitivity and 40% specificity. Assuming population characteristics similar to those of our development cohort, use of our questionnaire could decrease the use of bone densitometry by approximately 30%. Sensitivity and specificity can be varied by changing the level for referral for densitometry to provide the most cost-effective use within a particular healthcare setting. Thus use of our questionnaire, an inexpensive prescreening tool, in conjunction with physician assessment can optimize the use of bone densitometry and may lead to substantial savings in many healthcare settings where large numbers of women require evaluation for low bone mass.

Bone Density↗

Physical and kinetic characterization of recombinant human cholesteryl ester transfer protein.

Cholesteryl ester transfer protein (CETP) mediates the exchange of triglycerides (TGs), cholesteryl esters (CEs) and phospholipids (PLs) between lipoproteins in the plasma. In order to better understand the lipid transfer process, we have used recombinant human CETP expressed in cultured mammalian cells, purified to homogeneity by immunoaffinity chromatography. Purified recombinant CETP had a weight-average relative molecular mass (MW) of 69561, determined by sedimentation equilibrium, and a specific absorption coefficient of 0.83 litre.g-1.cm-1. The corresponding hydrodynamic diameter (Dh) of the protein, determined by dynamic light scattering, was 14 nm, which is nearly twice the expected value for a spheroidal protein of this molecular mass. These data suggest that CETP has a non-spheroidal shape in solution. The secondary structure of CETP was estimated by CD to contain 32% alpha-helix, 35% beta-sheet, 17% turn and 16% random coil. Like the natural protein from plasma, the recombinant protein consisted of several glycoforms that could be only partially deglycosylated using N-glycosidase F. Organic extraction of CETP followed by TLC showed that CE, unesterified cholesterol (UC), PL, TG and fatty acids (FA) were associated with the pure protein. Quantitative analyses verified that each mol of CETP contained 1.0 mol of cholesterol, 0.5 mol of TG and 1.3 mol of PL. CETP mediated the transfer of CE, TG, PL, and UC between lipoproteins, or between protein-free liposomes. In dual-label transfer experiments, the transfer rates for CE or TG from HDL to LDL were found to be proportional to the initial concentrations of the respective ligands in the donor HDL particles. Kinetic analysis of CE transfer was consistent with a carrier mechanism, having a Km of 700 nM for LDL particles and of 2000 nM for HDL particles, and a kcat of 2 s-1. The Km values were thus in the low range of the normal physiological concentration for each substrate. The carrier mechanism was verified independently for CE, TG, PL and UC in 'half-reaction' experiments.

Animals↗

A foodborne outbreak of gastroenteritis involving two different pathogens.

On the evening of October 10, 1990, many of the 474 inmates of a state prison in Florida began to experience symptoms of gastroenteritis. An investigation included interviews with inmates, evaluation of the kitchen and food-handling practices, cultures of leftover food, stool cultures, and cultures from the nares and skin lesions of food handlers. Of the 331 inmates interviewed, 215 (65%) had diarrhea, vomiting, or both. The median incubation period was 5 hours (range, 1-41 hours). Cases with onset of illness 8 or more hours after the evening meal were more likely than those with earlier onset to have had only diarrhea without vomiting (p < 0.001). Eating turkey at the evening meal on October 10 was associated with risk of illness (relative risk = 4.8, 95% confidence interval 1.7-13.7). Cases who became ill within 8 hours of the evening meal and those who became ill later were both more likely to have eaten turkey than those who did not become ill (p < 0.001 and p < 0.007, respectively). Salmonella infantis and enterotoxin-producing Staphylococcus aureus were both isolated from samples of leftover turkey, and S. infantis was isolated from 18 of 20 stool specimens. Cultures of the anterior nares and skin lesions of food handlers grew S. aureus, but phage typing failed to link these strains to the outbreak. Improper food-handling practices contributed to the development of this outbreak. This report highlights the importance of recognizing multiple-organism outbreaks, since the authors' recommendations for prevention of more cases depended upon knowing the risks associated with the distinct organisms and the possible sources of contamination.

Adult↗