Relationship between seizure frequency and costs and quality of life of outpatients with partial epilepsy in France, Germany, and the United Kingdom

PURPOSE: The relationship between seizure frequency and both health care costs and quality of life (QOL) was investigated in a retrospective, cross-sectional, multicenter study in France, Germany, and the United Kingdom. METHODS: Three hundred outpatients with stable partial epilepsy were approximately evenly distributed among five seizure-frequency groups, ranging from seizure-free in the last 3 months (group 1) to daily seizures (group 5). Economic data, obtained through patient interviews and record abstraction, comprised direct medical costs, direct nonmedical costs, and indirect costs for the preceding 3 months. Total societal costs in the three countries were pooled and converted to United States dollar equivalents. QOL was assessed through a self-administered questionnaire, the Functional Status Questionnaire (FSQ). RESULTS: Mean total costs increased from $780 in group 1 to $2,171 in group 5 (p = 0.0001), with significant increases in each cost category as seizure frequency increased. Greater seizure frequency also significantly (p = 0.0270) correlated with lower employment rates, which ranged from 57% in group 1 to 30% in group 5. QOL declined as seizure frequency increased. Particularly affected were basic and intermediate activities of daily living (ADL), mental health, social activity, and feeling about health. CONCLUSIONS: The study results show that higher seizure frequencies are associated with higher direct and indirect costs and with reduced QOL for patients with epilepsy.     

Identification of spherical virus particles in digitized images of entire electron micrographs

Interferon-gamma (IFN-gamma) has the most potent immunomodulatory activity of all the interferons. This phase II-B study was performed to define time- and dose-dependent immunomodulatory effects mediated by IFN-gamma in a subset of patients with melanoma treated in the dose-seeking therapeutic trial conducted by the Eastern Cooperative Oncology Group E4687 (13). The effects of IFN-gamma (Genentech, San Francisco, CA) were evaluated for phenotype and function of peripheral blood lymphocytes obtained twice prestudy, and on days 2, 9, and 29 of IFN-gamma therapy for 50 patients. Early significant increases in CD4/CD8 ratio (p = 0.001) were noted, largely due to a rise in CD4+ and fall in CD8+ T-cell populations sustained through day 29 at only the lowest dosage. Increased natural killer cell (NK) activity (p = 0.001 on day 9; p = 0.01 on day 29) was accompanied by durable increases in circulating activated NK cells (CD56+DR+% p = 0.001, day 9; p = 0.001, day 29). After initial depression of CD56+ and CD16+ cells on day 2, the total percent of CD56+ and CD16+ cells increased significantly by day 29. Increases in NK cell activity were maximal at doses > or =0.1 mg. Monocyte CD14+ expression of DQ+ rose early (p = 0.011 and 0.001 on days 2 and 9), accompanied by elevation in CD14+DR+ cells that was less significant. Immunomodulatory effects of IFN-gamma reported in this trial have major implications for interpretation of past and current clinical trials, and the design of future trials. This is the first trial in which IFN-gamma has been shown to have significant effects on the T-cell compartment of the immune system.     

Enhanced neointimal growth in cultured rabbit aorta following in vivo balloon angioplasty

We have used in vivo balloon catheterization in combination with in vitro organ culture to develop a model system for vascular neointima formation. A Fogarty balloon catheter was used to deendothelialize and rupture the internal elastic lamina of aortae in adult rabbits. After three d of recovery, aortae were harvested, divided into segments, and placed into organ culture. We obtained a daily index of cell proliferation in cultured vessels using [3H]thymidine incorporation into DNA. Also, segments were collected and processed for routine histology or immunohistochemistry. Aortic segments that had undergone ballooning 3 d before harvest and then cultured exhibited diffuse neointimal growth after several d in vitro, whereas those from sham-operated (nonballooned) rabbits showed generally only a single endothelial cell layer that is characteristic of normal intima. Aortae that were harvested, balloon-damaged in vitro, and then cultured exhibited no neointimal growth. The neointima that developed in cultured segments from in vivo ballooned rabbits was primarily of smooth muscle cell origin as determined by positive immunostaining for alpha-smooth muscle actin. The intima:media thickness ratios were significantly higher in aortic segments from ballooned rabbits at harvest and after 4 or 7 d in culture compared with those from nonballooned rabbits. Also, the [3H]thymidine index was higher in the in vivo ballooned aorta compared to non-ballooned or in vitro ballooned vessel. We conclude that ballooning in vivo followed by exposure to blood-borne elements produces an enhanced proliferative response in cultured vessels that is distinct from other in vitro models of neointimal growth.     

Rapid, sensitive procedure to determine buspirone levels in rat brains using gas chromatography with nitrogen-phosphorus detection

Reported here is a rapid, sensitive and relatively inexpensive procedure using gas chromatography with nitrogen-phosphorus detection (GC-NPD) to quantify buspirone levels in brains of rats. The analyte was directly extracted from brain homogenate with toluene after basification and then subjected to GC-NPD analysis using a capillary column. The calibration curves were linear over the range of 10 to 320 ng per 2 ml of brain homogenate, with typical r2 values >0.99. The assay was highly reproducible and gave peaks with excellent chromatographic properties.     

Mutational analysis of the Mu transposase. Contributions of two distinct regions of domain II to recombination

Mu transposase is a member of a protein family that includes many transposases and the retroviral integrases. These recombinases catalyze the DNA cleavage and joining reactions essential for transpositional recombination. Here we demonstrate that, consistent with structural predictions, aspartate 336 of Mu transposase is required for catalysis of both DNA cleavage and DNA joining. This residue, although located 55 rather than 35 residues NH2-terminal of the essential glutamate, is undoubtedly the analog of the second aspartate of the Asp-Asp-35-Glu motif found in other family members. The core domain of Mu transposase consists of two subdomains: the NH2-terminal subdomain (IIA) contains the conserved Asp-Asp-Glu motif residues, whereas the smaller COOH-terminal subdomain (IIB) contains a large positively charged region exposed on its surface. To probe the function of domain IIB, we constructed mutant proteins carrying deletion or substitution mutations within this region. The activity of the deletion proteins revealed that domains IIA and IIB can be provided by different subunits in the transposase tetramer. Substitution mutations at two pairs of exposed lysine residues within the positively charged surface of domain IIB render transposase defective in transposition at a reaction step after DNA cleavage but prior to DNA joining. The severity of this defect depends on the structure of the DNA flanking the cleavage site. Thus, these data suggest that domain IIB is involved in manipulating the DNA near the cleavage site and that this function is important during the transition between the DNA cleavage and the DNA joining steps of recombination.     

An enhanced,acoustic emission-based,single-fiber-composite test

In the single-fiber-composite (SFC) test, a fiber imbedded in a matrix is loaded in tension, resulting in a fragmentation of the fiber. In the conventional version of this test, the final fiber fragmentation length distribution is used with a micro-mechanical model to determine the average fiber/matrix interfacial shear stress. In the enhanced version of this test, one also determines the applied stress at each fiber fracture, and from this, one can evaluate the strength of the fiber at short gage lengths. In our measurement system, we utilize an acoustic emission (AE) technique to detect the fiber fractures and to locate the fiber breaks and so determine both the fiber failure stresses as well as the fiber fragmentation lengths while the test is in progress. Critical to the success of this test is a broadband AE system that utilizes point-like AE sensors, procedures for evaluatingin situ, the wavespeed of the first wave arrival and signal processing techniques for determining the arrival time of this signal as precisely as possible for a broad range of wave shapes. Here we describe the application of such an enhanced SFC test procedure to investigate the failure of a Nicalon fiber in an epoxy matrix.     

Effects of Composition and Environment on the Fracture of Fluoride Glasses

Indentation-crack-length procedures were used to determine the critical fracture toughness (K_IC) and the sensitivity to environmentally enhanced crack growth in heavy-metal fluoride glasses of varying chemical composition. The data show that while K_IC was more or less invariant with composition, some glasses were more susceptible to subcritical crack growth than others. The results are interpreted in terms of existing crack-growth models. A technique for predicting K_IC from fundamental atomic bonding and crystal-structure data for these glasses is discussed.     

Kinetic analysis of plasma VLDL-TG and VLDL-remnant-TG turnover in anesthetized rats

We have estimated the turnover and relative pool sizes of nascent-VLDL-TG and VLDL-remnants-TG in anesthetized rats. [1-¹⁴C]Palmitoyl- and [2-³H]glyceryl-labeled “VLDL”-TG (including nascent VLDL-TG and VLDL-remnants-TG) were prepared by injecting labeled palmitate and glycerol into donor rats. Labeled serum from these rats was then injected intravenously into nembutalized male rats and serial blood samples taken for 30 min. Special care was taken to define any early components in the labeled “VLDL”-TG disappearance curves. In other experiments, the donors were rendered functionally hepatectomized 30 min after injection of³H-glycerol and the endogenous labeled VLDL-TG was allowed to circulate 30–60 min before collection of the TG-labeled VLDL-remnants-containing serum. The latter was injected into 4 recipient nembutalized rats and the remnant-TG-turnover measured by serial sampling as above. In two cases,¹⁴C-“VLDL” and³H-VLDL-remnants were injected as a single bolus into ether-anesthetized rats. Despite its complex composition, “VLDL”-TG in most cases disappeared in a single exponential fashion for 30 min with an average half-life of 5.9 min in nembutalized and 2.8 in ether-anesthetized rats. VLDL-remnants-TG showed a more complex behavior, but contained a major rapid component with a mean t_1/2 of ca. 1.5 min in both groups. The data, analyzed by multicompartmental analysis, were fitted to a simple model in which turnover of a larger nascent VLDL-TG pool with formation of a more rapidly turning over smaller pool of VLDL-remnant-TG is the rate-limiting step in overall TG removal from the d<1.006 fraction of rat serum. The data are consistent with our theoretical prediction that under these conditions the kinetics of the VLDL-remnants cannot be resolved from analysis of the total composite “VLDL” (nascent plus remnant) pool.     

Trail-following responses of the Argentine ant,Iridomyrmex humilis (Mayr), to a synthetic trail pheromone component and analogs

Behavioral evidence indicates that (Z)-9-hexadecenal (Z9-16ALD) is a trail pheromone component ofIridomyrmex humilis, and that the true trail pheromone may be multicomponent. Trail-following responses ofI. humilis workers to several concentrations of syntheticZ9-16ALD, a constituent of the Pavan's gland, were found to be comparable to responses to gaster extract trails containing ca. 100 times lessZ9-16ALD. Of the five aldehyde analogs tested, only (Z)-7-hexadecenal (Z7-16ALD) elicited significant trail-following. However, following responses to severalZ9-16ALD-Z7-16ALD combinations were lower than responses toZ9-16ALD alone. Trails on filter paper of biologically relevant concentrations ofZ9-16ALD lose activity within 2 hr in the laboratory. The release rate ofZ9-16ALD measured from filter paper trails was 0.25 ± 0.10 pg/cm-sec. This was used to estimate the trail-following threshold for this compound of Argentine ant workers.     

The influence of branch length on the deformation and microstructure of polyethylene

The length and number of side chain branches have a profound influence on the microstructure and physical properties of polyethylene (PE). For a series of linear PE copolymers: environmental stress cracking resistance (ESCR), melting points, creep resistance and modulus, and equilibrium spherulite size were all found to increase with increasing branch length (methyl to hexyl) at a given density and molecular weight. It is proposed that (at a fixed molecular weight) branch length and branch concentration determine spherulite size and, consequently, spherulitic boundary areas, in which the dry crazing/voiding occurs during the incubation period of environmental stress cracking (ESC). At a fixed density, decreased spherulite size contributes to greater spherulite boundary slip and increased creep at low (less than 2 MPa) stresses.