Iron deficiency anemia in the elderly: the diagnostic process.

OBJECTIVE: To determine the effectiveness of physician probability estimates calculated on the basis of findings from history-taking and physical examination in the diagnosis of iron deficiency anemia in elderly patients. DESIGN: Prospective study. SETTING: Two community hospitals offering secondary and tertiary care. PATIENTS: A total of 259 patients over 65 years of age found to have previously undiagnosed anemia. MEASURES: Physician estimates of the likelihood of iron deficiency before (pretest probability) and after (post-test probability) the laboratory test results were available. The hemogram was available to the physicians when they made their pretest probability estimates. Because the serum ferritin level proved to be the most powerful of the laboratory test results studied, the likelihood ratios associated with the post-test estimates were compared with the ratios associated with the serum ferritin level. MAIN RESULTS: The post-test probability estimates were influenced by the serum ferritin level and the pretest estimates. The post-test estimates derived from the findings obtained through history-taking and physical examination and the laboratory test results (including the serum ferritin level) were slightly less accurate in predicting iron deficiency than the serum ferritin level alone. Nevertheless, a model in which the pretest estimates were used in addition to the serum ferritin level to predict iron deficiency proved to be more powerful than the serum ferritin level alone (p = 0.006). This indicated that the limitations of the post-test estimates were due to a misinterpretation of the serum ferritin level and that the findings from history-taking and physical examination added important diagnostic information. CONCLUSIONS: Physicians must be aware of test properties to provide optimal care to their patients. If test results are properly interpreted, pretest probabilities derived from findings obtained through history-taking and physical examination can add useful information that will lead to more accurate diagnoses.     

Synthesis of a Pseudo-Disaccharide Library and Its Application to the Characterisation of the Heparanase Catalytic Site

A novel methodology is described for the efficient and divergent synthesis of pseudodisaccharides, molecules comprising of amino carbasugar analogues linked to natural sugars. The methodology is general and enables the introduction of diversity both at the carbasugar and the natural sugar components of the pseudodisaccharides. Using this approach, a series of pseudodisaccharides are synthesised that mimic the repeating backbone unit of heparan sulfate, and are tested for inhibition of heparanase, a disease-relevant enzyme that hydrolyses heparan sulfate. A new homology model of human heparanase is described based on a family 79 β-glucuronidase. This model is used to postulate a computational rationale for the observed activity of the different pseudodisaccharides and provide valuable information that informs the design of potential inhibitors of this enzyme.     

A method for the measurement of the sedimentation coefficient and molecular weight of microgram quantities of proteins in 6 M guanidine hydrochloride

A technique has been perfected for measuring the sedimentation coefficient of microgram quantities of a reduced protein in 6 M guanidine hydrochloride. The protein is sedimented through a gradient of 5-8 M guanidine-HCl in the presence of dithiothreitol in a SW 50.1 swinging-bucket rotor. Run conditions are calibrated by a simultaneous measurement using a single reference protein. Thus, the need for running a calibration curve involving several standard proteins simultaneously with a sample is eliminated. Because of the trace quantity of protein used, the technique yields an estimate of the sedimentation coefficient at zero concentration (s0) directly without extrapolation. Since s0 is a function of the molecular weight of a reduced protein in this solvent, the method also allows an estimate of the subunit molecular weight of the protein. The results of the application of the method to known proteins are reported.     

The effect of inhibitors of RNA and protein synthesis on dibutyryl cyclic AMP mediated morphological transformations of Chinese hamster ovary cells in vitro

Morphological transformation of cultured Chinese hamster ovary cells (CHO-Kl) produced by the addition and removal of dibutyryl cyclic AMP plus testosterone are unaffected by inhibition of either RNA synthesis or protein synthesis.