Evaluation of epicardial fat tissue thickness as a marker of cardiovascular risk in patients with subclinical hypothyroidism.

BACKGROUND: Epicardial fat thickness (EFT) has been evaluated as a marker of cardiovascular disease, with good correlation with classical cardiovascular risk factors in the general population. The aim of this study was to evaluate the EFT in subclinical hypothyroidism (SCH), in comparison to a group without thyroid dysfunction. METHODS: A cross-sectional study was performed with 100 participants, including 52 SCH patients and 48 individuals without any thyroid dysfunction (euthyroid group-EU). Transthoracic echocardiography (TE), thyroid hormone levels, lipid profile, and assessment of body composition by bioelectrical impedance (BIA) and anthropometry were measured in all subjects. RESULTS: The SCH and EU groups were comparable with respect to age, gender, and Framingham risk scores. Serum thyroid-stimulating hormone (TSH) was 6.7 ± 1.4 mIU/L in the SCH group and 2.0 ± 0.84 mIU/L in the control group. EFT was similar in both groups (SCH 3.5 ± 1.3 mm, EU 3.5 ± 1.1 mm, p = 0.43). EFT showed a slight trend for a positive correlation with serum TSH in the SCH group (r s = 0.263, p = 0.05). EFT correlated with the body fat percentage in the SCH group (r s = 0.350, p = 0.03) and EU group (r s = 0.033, p = 0.04). EFT in this cohort was not independently correlated to changes in TSH and Framingham risk score. CONCLUSIONS: EFT determination by TE does not seem to be a good marker of cardiovascular risk in SCH patients with serum TSH <10.0 mIU/L and no pre-existing cardiovascular morbidity.

Boundary element solution of the linear Poisson-Boltzmann equation and a multipole method for the rapid calculation of forces on macromolecules in solution.

The Poisson-Boltzmann equation is widely used to describe the electrostatic potential of molecules in an ionic solution that is treated as a continuous dielectric medium. The linearized form of this equation, applicable to many biologic macromolecules, may be solved using the boundary element method. A single-layer formulation of the boundary element method, which yields simpler integral equations than the direct formulations previously discussed in the literature, is given. It is shown that the electrostatic force and torque on a molecule may be calculated using its boundary element representation and also the polarization charge for two rigid molecules may be rapidly calculated using a noniterative scheme. An algorithm based on a fast adaptive multipole method is introduced to further increase the speed of the calculation. This method is particularly suited for Brownian dynamics or molecular dynamics simulations of large molecules, in which the electrostatic forces must be calculated for many different relative positions and orientations of the molecules. It has been implemented as a set of programs in C++, which are used to study the accuracy and speed of this method for two actin monomers.

Future directions for combining molecular and continuum models in protein simulations.

In order to perform useful computer simulations on protein molecules, models that combine atomistic and continuum approaches will be necessary. The use of continuum models will reduce the number of system variables and allow studies of longer time scales. On the other hand, one will still need to retain atomic detail in certain parts of the protein molecule, such as an enzyme active site. Most of the important advances to date have been continuum models of the surrounding solvent, but simplified descriptions of the protein itself also are being developed. Finally, in order to study these several different levels of complexity simultaneously in a single simulation, it will be necessary to use modern software engineering techniques.

Neo-isolationism, balanced-budget conservatism, and the fiscal impacts of immigrants.

"A rise in neo-isolationism in the United States has given encouragement to a new fiscal politics of immigration. Growing anti-immigrant sentiment has coalesced with forces of fiscal conservatism to make immigrants an easy target of budget cuts. Limits on legal alien access to social welfare programs that are contained in the 1996 welfare and immigration reform acts seem motivated not so much by a guiding philosophy of what it means to be a member of American society as by a desire to shrink the size of the federal government and to produce a balanced budget. Even more than in the past, the consequence of a shrinking welfare state is to metamorphose legal immigrants from public charges to windfall gains for the federal treasury."

Electrostatic channeling of substrates between enzyme active sites: comparison of simulation and experiment.

Recent simulation work has indicated that channeling of charged substrates between the active sites of bifunctional enzymes or bienzyme complexes can be significantly enhanced by favorable interactions with the electrostatic field of the enzymes. The results of such simulations are expressed in terms of transfer efficiencies, which describe the probability that substrate leaving the active site of the first enzyme will reach the active site of the second enzyme before escaping out into bulk solution. The experimental indicators of channeling, on the other hand, are factors such as a decrease in the transient (lag) time for appearance of the final product of the coupled enzyme reaction or a decrease in the susceptibility of the overall reaction rate to the presence of competing enzymes or competitive inhibitors. The work reported here aims to establish a connection between the transfer efficiencies obtained from simulation, with the above-mentioned experimental observables. This is accomplished by extending previously reported analytical approaches to combine the simulated transfer efficiency with the Michaelis-Menten kinetic parameters Km and Vmax of the enzymes involved; expressions are derived to allow both transient times and steady state rates to be calculated. These results are applied to the two systems that have been studied both theoretically and experimentally. In the first case, that of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS), the experimentally observed decrease in transient times is found to be consistent with a transfer efficiency of >/=80%. In the second case, that of a citrate synthase-malate dehydrogenase fusion protein, a transfer efficiency of 73% is consistent with the experimental transient time measurements. Separate and independent analysis of the effects of adding the competing enzyme aspartate aminotransferase gives a transfer efficiency of 69%, in excellent agreement with the transient time results. The transfer efficiencies thus obtained from experimental results are in both cases in good agreement with those obtained from simulations that include electrostatic interactions. One important discrepancy between simulation and experiment, is however, found in the reported effects of adding a competitive inhibitor in the DHFR-TS system: qualitatively different results are expected from the theoretical analysis. A possible reason for this apparent contradiction is discussed.

Weighted-ensemble Brownian dynamics simulations for protein association reactions.

A new method, weighted-ensemble Brownian dynamics, is proposed for the simulation of protein-association reactions and other events whose frequencies of outcomes are constricted by free energy barriers. The method features a weighted ensemble of trajectories in configuration space with energy levels dictating the proper correspondence between "particles" and probability. Instead of waiting a very long time for an unlikely event to occur, the probability packets are split, and small packets of probability are allowed to diffuse almost immediately into regions of configuration space that are less likely to be sampled. The method has been applied to the Northrup and Erickson (1992) model of docking-type diffusion-limited reactions and yields reaction rate constants in agreement with those obtained by direct Brownian simulation, but at a fraction of the CPU time (10(-4) to 10(-3), depending on the model). Because the method is essentially a variant of standard Brownian dynamics algorithms, it is anticipated that weighted-ensemble Brownian dynamics, in conjunction with biophysical force models, can be applied to a large class of association reactions of interest to the biophysics community.

Gas--liquid chromatographic determination of free dimethindene in human serum and urine at low concentrations.

A simple method for the determination of dimethindene down to a concentration of 10 ng/ml in human urine and serum is described. After the addition of an internal standard, the dimethindene is extracted as the free base with pentane. Measurements are made directly by gas--liquid chromatography using a flame ionization detector.

Investigative reporting cuts risk at psychiatric facility.

Risk management program uses an investigation report as the primary tool for collecting data about an incident, analyzing that data, and translating the information into strategies for change.

Repayment regulations limit use of nonphysicians.

Hospital planners are advised to think of physician's assistants (PAs) and nurse practitioners (NPs) as part of the health care team, but to be cautious of enlarging their roles beyond the scope of licensure laws and reimbursement regulations.

Strategic strike management helps hospital to carry on.

During a strike, a hospital's administration has the responsibility for minimizing disruption of patient care. Preparation for a strike should include development of a contingency plan whereby additional duties are assigned equitably among staff members, lines of communication are reinforced, and services are shared with neighboring hospitals.

Cytochrome P-450 content and mixed-function oxidation by microsomes from rabbit alveolar macrophages.

Cytochrome P-450 content and p-nitroanisole demethylation (a mixed-function oxidation) were investigated in the microsomal fraction from rabbit alveolar macrophages. The content of cytochrome P-450 was 0.13 +/- 0.024 (mean +/- S.E., n = 9) nmol/mg protein and was not stimulated by pretreatment of rabbits with chlorpromazine. Pretreatment with BCG resulted in decreased cytochrome P-450-specific content, suggesting that the microsomal protein pool was diluted by de novo synthesis of noncytochrome proteins. Demethylation of p-nitroanisole by alveolar macrophage microsomes during a 1 hr incubation was 17.1 +/- 1.4 nmol X hr-1 X mg protein-1. The microsomal fraction from homogenates of whole lungs had a cytochrome P-450 content of 0.32 +/- 0.078 nmol/mg protein and p-nitroanisole demethylase activity of 26.6 +/- 8.7 nmol X hr-1 X mg protein-1. The results indicate the presence of cytochrome P-450 in rabbit alveolar macrophages and show that the microsomal fraction can catalyze a mixed-function oxidation reaction. Comparison of alveolar macrophage and whole lung microsomal preparations indicates that alveolar macrophage cytochrome P-450 comprises a minor fraction of the total pulmonary pool.

The effect of a target date based utilization review program on length of stay.

This study was conducted to determine whether implementation of a specific formalized concurrent utilization review system which involved making a prior determination of length of stay had any more effect on average length of stay than continuance of a utilization review method not involving assignment of such a target date. The system studied was the Pre-Discharge Utilization Review (PDUR) program used for Medicaid patients in Pennsylvania. Analysis was conducted using discharge abstracts for Medicaid patients under age 65 who were discharged with one of 14 common diagnoses for certain Allegheny County hospitals in 1972 and 1973. Comparisons were made for each individual diagnosis to control for possible differences in case mix. Results indicate that there was no general reduction in length of stay which could be attributed to the PDUR program.

Evidence for lipid synthesis by the dihydroxyacetone phosphate pathway in rabbit lung subcellular fractions.

Lipid synthesis by the lung requires a 3-carbon skeleton that can be provided by sn-glycerol-3-phosphate derived from glycolysis. This study investigated whether acylation of dihydroxyacetone-phosphate can serve as an alternate pathway for lung lipid synthesis. Rabbit lung microsomal and mitochondrial fractions were incubated with radiolabelled sn-glycerol-3-P and/or dihydroxyacetone-P. Palmitoyl CoA was used as acyl donor. The lipid fraction was subsequently isolated and radioactive incorporation was determined. Glycerol-3-P and dihydroxyacetone-P were both incorporated into the lipid fraction when each substrate was present alone. During incubation in the presence of equimolar concentrations of both substrates dihydroxyacetone-P accounted for 41 per cent of the total incorporation. These results show that acylation of dihydroxyacetone phosphate is a potential alternate to the glycerol-3-phosphate pathway for lung lipid synthesis.