Defined contribution: it's inevitable.
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Cost Sharing↗
Biomedical subjects
R Battistella
Publications and source records attributed to R Battistella.
Mitomycin C pharmacokinetics in patients with recurrent or metastatic colorectal carcinoma.
The pharmacokinetics of mitomycin C as a single agent have been determined in 25 treatment courses given to 18 patients with recurrent or metastatic colorectal carcinoma using a high performance liquid chromatography (HPLC) assay to analyze plasma and urine samples. The plasma pharmacokinetics conformed to a two-compartment linear model in 21 of 25 courses monitored with a mean t1/2 lambda 1 of 9.8 +/- 1.2 (SEM) min and mean t1/2 lambda z of 64.1 +/- 8.9 (SEM) min. The large variation observed in t1/2 lambda z was not related to dose or treatment, but an interaction of these two factors approached significance (p = 0.057). Renal excretion in the 12 courses in which it was determined averaged only 2.3% of the total administered dose during the first 4 h monitored and no mitomycin C metabolites were detected in plasma or urine by the HPLC technique used. The most common toxicity, thrombocytopenia, did not correlate with t1/2 lambda z or the area under the curve. This may be due to a failure to monitor active metabolites of mitomycin C; other factors besides plasma drug concentrations that mediate toxicity towards marrow elements; or the small number of courses associated with thrombocytopenia (less than 100,000/mm3). Our study indicates that an interaction of drug dose and treatment course may be associated with increasing t1/2 lambda z; the renal clearance contributes a small component of mitomycin C elimination; metabolites of mitomycin C cannot be detected by the present HPLC technique; and routine monitoring of mitomycin C using present methods cannot be recommended for clinical use to predict toxicity.
Aged↗
Altered cholesterol ester proportions in embryonic tissues of dystrophic chicken.
The concentrations of cholesterol esters in tissues of dystrophic chicken embryos are altered from normal. These changes are accompanied by significant changes in the proportions of the esterified fatty acids (the fatty acid profile). In serum and pectoral muscles there is a shift to a higher proportion of unsaturated fatty acids (in particular 18:1). Thigh muscle esters are little changed and in liver and brain the proportion of unsaturated fatty acids decreases.
Animals↗
2-Hydroxylaminoimidazoles--unstable intermediates in the reduction of 2-nitroimidazoles.
An unstable 2-hydroxylaminoimidazole (2-hydroxylamino-1-methylimidazole) was prepared by the reaction of 2-fluoro-1-methylimidazole with hydroxylamine. This substance was sufficiently stable (half-life of 1-2 days) in acid solutions to be observed and characterized by NMR spectroscopy; decomposition at neutrality was, however, rapid (half-life of 1-10 min). Radiochemical and electrochemical reduction experiments were carried out at pH 4 and pH 7 with 2-nitro-1-methylimidazole and misonidazole [1-(3'-methoxy-2'-hydroxypropyl)-2-nitroimidazole]. A four electron stoichiometry was found in every case. The pH 4 reduced product was identified as the 2-hydroxylamino derivative (greater than 80% yield). The pH 7 reduced solutions, on the other hand, showed no aromatic 1H NMR signals, suggesting that a simple imidazole ring was no longer present. A shift to pH 7 of the hydroxylamine produced at pH 4, however, resulted in very similar NMR spectra. The conclusion, therefore, is that the hydroxylamine was produced initially on reduction of the nitroimidazole, but it was not stable.
Chemical Phenomena↗
The oxygen dependence of the reduction of nitroimidazoles in a radiolytic model system.
Radiation chemical reductions using eaq- and CO2- have been carried out in the presence of oxygen with metronidazole, p-nitroacetophenone, misonidazole and three other 2-nitroimidazoles. Low concentrations of oxygen were found to effectively inhibit the reduction of the first two compounds while much higher concentrations of oxygen were required for all of the 2-nitroimidazoles. These results parallel in vitro and in vivo experiments with metronidazole and misonidazole which also indicate that the reduction of the latter is significantly less inhibited by oxygen. Kinetic modelling of the radiochemical system suggests that the explanation for the differences lies in different reactions of the nitro radical anions; it appears that the anion derived from metronidazole undergoes disproportionation while that derived from misonidazole undergoes a unimolecular decay.
Acetophenones↗
Role of Ia antigens in graft vs. host reactions. II. Molecular and functional analysis of T cell alloreactivity by the characterization of host Ia antigens on alloactivated donor T cells.
Graft vs. host response (GVHR)-activated donor T cells bind to stimulatory host cell-derived Ia antigens. Radioimmune cell-binding assays demonstrate that activated donor T cells acquire both host I-A and I-E alloantigens on their surface. Approximately threefold to fivefold less I-E products than I-A products are transferred. Immunoprecipitation and one-dimensional and two-dimensional gel electrophoresis analyses show that radioiodinated alpha and beta polypeptide chains of both I-A and I-E-encoded host Ia molecules may be transferred in an apparently structurally unaltered form from host cells to donor cells. Biosynthetic studies indicate that [35S]methionine-labeled activated donor T cells do not synthesize Ia antigens of the donor haplotype. Functional analyses with fluorescence-activated cell sorter sorted donor T cell subpopulations show that donor T cells that bind host I-A antigens preferentially cooperate with nonimmune host B cells. Donor T cells that do not bind detectable amounts of host I-A antigens preferentially help nonimmune donor B cells. By contrast, donor T cells that either bind or do not bind host I-A antigens display no H-2-restricted interaction and help both donor and host immune B cells. These data reveal that the Ia antigen-binding specificity of distinct functional subpopulations of alloactivated donor T cells regulates their I-region-restricted (self or allo) helper activity for nonimmune B cells but not immune B cells. Furthermore, they suggest that T cell-macrophage and T cell-B cell collaboration is mediated by a complementary anti-Ia:Ia receptor:ligand type of interaction in which the receptor of a T cell binds to the ligand of an antigen-presenting macrophage and/or B cell.
Animals↗
In vitro analysis of allogeneic lymphocyte interaction. V. Identification and characterization of two components of allogeneic effect factor, one of which displays H-2-restricted helper activity and the other, T cell-growth factor activity.
An allogeneic effect factor (AEF) derived from mixed lymphocyte reaction (MLR) cultures of alloactivated A.SW (H-2s) responder T cells and irradiated A/WySn (H-2a) stimulator spleen cells helps an in vitro primary anti-erythrocyte plaque-forming cell PFC response of BALB/c nude spleen cels and also A/WySn but not A.SW T cell-depleted spleen cells. AEF activity is adsorbed by anti-Ik and anti-I-Ak but not by anti-I-Jk, anti-I-ECk, and anti-Is. Gel filtration of ACA 54 resolves AEF into two main components that which appear in the 50,000- to 70,000-mol wt (component I) and 30,000- to 35,000-mol wt (component II) regions, respectively. Component I has a mol wt of 68,000, elutes from DEAE-Sephacel at 0.05-0.1 M NaCl, and has an isoelectric point (pI) of 5.8. It helps A/WySn but not A.SW B cells and, therefore, is H-2 restricted. Component II is not H-2 restricted, because it helps both A.SW and A/WySn B cells. It also stimulates (a) the growth of a long-term cytotoxic cell line in vitro, (b) Con A-induced thymocyte mitogenesis, and (c) the generation of cytotoxic T cells. The latter three properties of component II are not shared by component I. In addition, component II elutes from DEAE-Sephacel at 0.15-0.2 M NaCl and has a pI of 4.3 and 4.9. Ia determinants and Ig VH, CH, L-chain, and idiotypic determinants are not present on either component I or component II. The properties of component II are identical to that of a T cell growth factor produced by Con A-stimulated spleen cells. It is suggested that the H-2-restricted component I of AEF might be an MLR-activated responder T cell-derived Ia alloantigen receptor.
Animals↗
Health cost containment.
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Economics, Medical↗
Health services reforms: political and managerial aims--an international perspective.
Health policy everywhere is in flux. In marked contrast with the impenetrable orthodoxy and inaction characteristic of past decades, health policy currently is in the midst of large-scale upheaval. Many of the fundamental assumptions and principles that long guided health-sector development are in the process of being turned upside down. Whether a country is rich or poor, it matters not. Virtually every country either has or is contemplating major reforms in its provisions for the organization and financing of health services. Moreover, the differences in health services structure which divided nations, are becoming smaller--to the point where formerly shunned international exchanges now are considered useful mediums for the exposition of common tensions and the exploration of choices for adapting health care to complex and new economic realities.
Economic Competition↗
The future of employment-based health insurance.
A transformation of employment-connected health insurance from a defined benefit to defined contribution arrangement is projected based on new economic realities affecting the competitiveness of the business environment. This article discusses those new realities along with the future of employment-based health insurance. The business of American business is profits, but, to the detriment of that goal, for the past half century business has also been in the business of providing health insurance for workers. However, in light of previously unencountered pressures on profits, employers are realizing they cannot afford to continue the practice of paying for and overseeing the provision of healthcare benefits to employees amid increasing premiums, state and federal mandates, the overbearing cost of managing healthcare benefits, and the threat of loss of protection under ERISA. Yet, the political and social pressures on businesses to continue to provide health insurance are formidable, perhaps impregnable, barriers to complete withdrawal of what has come to be thought of as a "right" of employees. Companies are anxious to find alternatives to the status quo, but any feasible alternative must cost less, require less administrative oversight, and ensure that employees still maintain a measure of choice. Two possible solutions for American businesses are adoption of (1) a "medical savings account" system, or (2) a "voucher" system. Either system would result in lower costs and greater fiscal stability for both employers and employees. They would also remove much of the responsibility for healthcare decisions from employers and place it in the hands of the employees. But, perhaps the greatest contribution of either system would be the reduction in moral hazard and its inflationary effect on medical costs.
Commerce↗