[Assessment of hydroxylated metabolites of polychlorinated biphenyls and polychlorinated dibenzofurans as potential estrogens by yeast two-hybrid system].

The estrogenic activities of several hydroxylated metabolites of PCBs and PCDFs were investigated by yeast two-hybrid assay based on the ligand-dependent interaction of estrogen receptor with coactivator. For the hydroxylated PCBs, the order of estrogenic potency was 4-OH-2',4',6'-triCB > 4-OH-4'-monoCB, 4-OH-biphenyl. These compounds were evaluated as 10(3) to 10(4) less potent than 17 beta-estradiol based on the concentrations of test compounds showing 10% activity of 10(-7) M 17 beta-estradiol. 2-OH-3',4,4'-triCB, 4-OH-2',3,4'-triCB and 3-OH-/4-OH-2,2',5,5'-tetraCB, the metabolites of 2,2',5,5'-tetraCB were inactive as estrogens at the highest concentrations used in this study (10(-5) M). Also 4-OH-3,3',4',5-tetraCB, the metabolite of 3,3',4,4'-tetraCB was inactive as estrogen, indicating that this hydroxylated metabolite did not take part in the estrogenic activity of 3,3',4,4'-tetraCB. OH group at 4-position of biphenyl was necessary for the expression of estrogenicity, but one or two chloro-substitution adjacent to OH group inhibited the activity. For the hydroxylated PCDFs, 8-OH-2-monoCDF, 7-OH-3,4-diCDF, 8-OH-3,4-diCDF, 8-OH-3,4,6-triCDF and 3,8-(OH)2-2-monoCDF exhibited estrogenic activity. The estrogenic activity of 3,8-(OH)2-2-monoCDF was comparable to those of 4-OH-2',4',6'-triCB and 4-nonylphenol (mixture of compounds with branched sidechain). The order of activity was 3,8-(OH)2-monoCDF > 8-OH-3,4-diCDF, 7-OH-3,4-diCDF > 8-OH-2-monoCDF, 8-OH-3,4,6-triCDF. These compounds were evaluated as 2.5 x 10(3) to 3 x 10(4) less potent than 17 beta-estradiol. On the other hand, no estrogenic activity was observed for 2-OH-dibenzofuran, 3-OH-2,8-diCDF, 6-OH-3,4-diCDF and 9-OH-3,4-diCDF at concentrations as high as 10(-4) M. Substitution of OH group at 2(8)- or 3(7)-position of dibenzofuran and no chloro-substitution adjacent to OH group was required for the estrogenic activity.

Health care trends, Part I. The promise and perils of evidence-based medicine ... panel discussion.

Numerous studies have demonstrated that there are wide variations in the way physicians manage similar patients. This suggests that an evidence-based approach could lead to better outcomes with less cost. But practicing evidence-based medicine requires new skills, such as using computerized databases and applying the rules of evidence to primary and integrative studies in the medical literature. The progress of evidence-based medicine will depend in large measure on how quickly these new skills can be developed and integrated into the practice environment. Here's how six experts see the promise and the perils of evidence-based medicine, now and in the new millennium. Part 2 of the panel discussion will explore the new provider team, which includes nurses and, more recently, pharmacists, who are collaborating with physicians to provide disease management and drugs therapy management services.

Hepatocyte growth factor in assessment of acute pancreatitis: comparison with C-reactive protein and interleukin-6.

Serum levels of hepatocyte growth factor (HGF), C-reactive protein (CRP), and interleukin-6 (IL-6) were determined at the time of admission in 38 patients with acute pancreatitis. The clinical utility of HGF for the detection of severe pancreatitis and for predicting prognosis, bacterial infection (infected pancreatic necrosis or sepsis), and organ dysfunction (liver, kidney, and lung) during the clinical course of acute pancreatitis was compared with the clinical utility of CRP and IL-6 by analysis of receiver operator characteristic (ROC) curves. The optimum cutoff levels of HGF for severity, prognosis, infection, hepatic dysfunction, renal dysfunction, and respiratory dysfunction were 0.9, 1.1, 1.0, 1.1, 1.1, and 1.0 ng/ml, respectively. HGF was as useful as CRP and more useful than IL-6 for detection of severe pancreatitis and for predicting hepatic dysfunction. Moreover, HGF was more useful than CRP or IL-6 for predicting prognosis, renal dysfunction, and respiratory dysfunction. However, for predicting infection, CRP was more useful than HGF. These results suggest that serum HGF levels on admission may be a useful new clinical parameter for determining the prognosis of acute pancreatitis and that HGF may be closely related to the organ dysfunction of acute pancreatitis.

Use of whole-body imaging using Tc-99m RBC in patients with soft-tissue vascular lesions.

We investigated the usefulness of whole-body imaging as an adjunct to spot imaging in soft-tissue vascular lesions, such as hemangiomas and vascular malformations. Spot imaging of the known lesion and whole-body imaging were performed 1-3 hours after the injection of Tc-99m RBC in 42 patients with soft-tissue vascular lesions. Whole-body imaging was considered to be useful in only two patients, who had multiple distant occult lesions in addition to large known lesions. It was suggested that the routine addition of whole-body imaging is not cost effective in patients with soft-tissue vascular lesions, although it may be beneficial for detecting occult lesions in patients with hemangiomas.

Assessment of the cerebrovascular response to acetazolamide using 99mTc-DTPA-HSA: methodological considerations.

We have reported methods of assessing the cerebrovascular response to acetazolamide using 99mTc-DTPA-HSA and their usefulness in evaluating cerebral hemodynamics. Several problems of this technique were investigated in 10 normal subjects. Following 99mTc-DTPA-HSA injection, dynamic imaging of the anterior head view was performed for 25 to 50 minutes, and 10 minutes after the beginning of imaging, 1,000 mg of acetazolamide was infused intravenously. Venous blood samples were obtained during the imaging period to estimate the blood retention of 99mTc-DTPA-HSA. Radioactivity in the head increased for about 10 minutes following acetazolamide infusion, then decreased slowly. The declining phase almost disappeared after correction for the blood clearance of 99mTc-DTPA-HSA, indicating stability of the vasodilatory effect of acetazolamide. Dilatation index, the percent increase in activity, was a little smaller after correction, but was closely correlated with the index without correction. There was a high correlation between dilatation indices obtained by two analyses, including ROI setting and visual determination of the peak, of the same data. In conclusion, neither blood clearance of 99mTc-DTPA-HSA nor subjective analysis considerably impairs the reliability of the dilatation index, and blood volume in the head from about 15 to 40 minutes after acetazolamide injection is stable and suitable for SPECT.