The Medical Expenditure Panel Survey: a national health information resource

This article describes the Medical Expenditure Panel Survey (MEPS), the third in a series of nationally representative surveys of medical care use and expenditures sponsored by the Agency for Health Care Policy and Research. The MEPS is designed to provide extensive data on the types of health care services American use, how frequently they use them, how much is paid for the services, and who pays for them. It also will provide information on the types and costs of private health insurance available to the U.S. population. The survey is unparalleled in its degree of detail, as well as its ability to link medical care use, payments, and health insurance coverage to specific survey respondents and their families. It allows analysts to examine how individual and family characteristics, including the characteristics of their health insurance, affect medical care use and spending. This article discusses each of the MEPS components, focusing on design enhancements that have been made since the survey was last conducted nearly a decade ago.     

Persistent thrombin generation in humans during specific thrombin inhibition with hirudin

BACKGROUND: The degree to which antithrombotic drugs suppress thrombin generation is unknown. Because hirudin, unlike antithrombin III, binds intravascular thrombin rapidly and selectively to yield a circulating inactive complex of 3- to 4-hour half-life, we used intravenous hirudin in humans to investigate the course of thrombin generation during and early after anticoagulation with this potent, direct antithrombin. METHODS AND RESULTS: Intravascular thrombin was measured with an ELISA for the thrombin-hirudin complex formed during and for 18 hours after stopping a 6-hour infusion of hirudin at 0.1, 0.2, and 0.3 mg.kg-1.h-1 in three groups of six patients each. With free hirudin in 20- to 10,000-fold molar excess of thrombin and peak activated partial thromboplastin times of 2.3 to 3.0 times baseline, mean plasma thrombin-hirudin complex increased from 794 +/- 85 pg/mL (mean +/- SEM) 15 minutes after the start of the infusion to 1617 +/- 151 pg/mL at 6 hours of infusion to 2667 +/- 654 pg/mL at 24 hours. During the 24-hour observation period, plasma concentration of fragment 1.2 (the peptide released during conversion of prothrombin to thrombin) never fell below baseline but rather increased transiently during the hirudin infusion. Plasma concentrations of thrombin-antithrombin III complex (in ng/mL) decreased from 4.34 +/- 0.40 at baseline to 1.64 +/- 0.13 at 6 hours (P < .001) and gradually increased after stopping the infusion to 5.7 +/- 0.87 at 24 hours (nonsignificant compared with baseline). CONCLUSIONS: Measurement of thrombin-hirudin complex may be used as a marker of thrombin generation in humans. Persistent accumulation of thrombin-hirudin complex and generation of fragment 1.2 during and after completion of potent anticoagulation with hirudin suggest thrombin generation is not blocked by high-affinity thrombin inhibition. The persistent formation of thrombin during declining plasma levels of hirudin may contribute to the pathogenesis of rethrombosis early after antithrombin therapy or during inadequate anticoagulation.     

Novel sequence organization and insertion specificity of IS605 and IS606: chimaeric transposable elements of Helicobacter pylori

We have used PKH26 dye, which is incorporated stably into the membrane of cells, to determine, using flow cytometry, lymphocyte proliferative responses to the antigen tetanus toxoid in fresh and cryopreserved samples. Measuring cell proliferation with this dye has advantages over either 3H-thymidine or Bromodeoxyuridine (BrdU). Whereas the existing methods measure proliferation at a single time point, PKH26 gives a cumulative measure of cell proliferation. As PKH26 is incorporated into the cell membrane, cells do not have to be permeabilised to allow dye incorporation into a cytoplasmic compartment. Most importantly, PKH26 can be used in combination with monoclonal antibodies to surface markers on mixed populations of cells, to determine the proliferation of individual subpopulations, without the need for prior cell fractionation. We also show that PKH26 can be used with similar efficacy in both fresh and cryopreserved samples. In addition since PKH26 is a cumulative measure of proliferative responses we were able to show that restimulation of the dividing population in vitro with fresh antigen presenting cells (APC) and antigen permits characterisation of a further proliferating cell population. The use of PKH26 dye in combination with cell phenotyping and measurement of cytokine production at the single cell level will prove a powerful tool for multiparameter analyses of cellular responses to antigen.     

Interleukin (IL)-10, IL-12, and interferon-gamma production in primary and memory immune responses to varicella-zoster virus

Varicella immunization provided the opportunity to examine the kinetics of interleukin (IL)-10, IL-12 and interferon (IFN)-gamma production elicited during primary in vivo sensitization with proteins of varicella-zoster virus (VZV), a common human herpesvirus. VZV-specific IFN-gamma release and T cell proliferation were elicited by immunization and persisted through 15 months of follow-up. The induction of VZV-specific T cells and IgG antibodies was accompanied by transient increases in IL-10 and IL-12 production. T cell proliferation to VZV was significantly lower in adults at 15 months than in vaccinated children or naturally immune subjects and correlated with lower IFN-gamma responses in individual vaccinees. After primary immunity was induced, continued IL-12 production was not necessary to maintain the predominant Th1-type response elicited by VZV. Cytokine profiles observed during primary in vivo sensitization to VZV suggest that parallel increases in IFN-gamma and IL-10 may be important in the induction of immunity to some viral pathogens.     

The cell tropism of human immunodeficiency virus type 1 determines the kinetics of plasma viremia in SCID mice reconstituted with human peripheral blood leukocytes

Most individuals infected with human immunodeficiency virus type 1 (HIV-1) initially harbor macrophage-tropic, non-syncytium-inducing (M-tropic, NSI) viruses that may evolve into T-cell-tropic, syncytium-inducing viruses (T-tropic, SI) after several years. The reasons for the more efficient transmission of M-tropic, NSI viruses and the slow evolution ofT-tropic, SI viruses remain unclear, although they may be linked to expression of appropriate chemokine coreceptors for virus entry. We have examined plasma viral RNA levels and the extent of CD4+ T-cell depletion in SCID mice reconstituted with human peripheral blood leukocytes following infection with M-tropic, dual-tropic, or T-tropic HIV-1 isolates. The cell tropism was found to determine the course of viremia, with M-tropic viruses producing sustained high viral RNA levels and sparing some CD4+ T cells, dual-tropic viruses producing a transient and lower viral RNA spike and extremely rapid depletion of CD4+ T cells, and T-tropic viruses causing similarly lower viral RNA levels and rapid-intermediate rates of CD4+ T-cell depletion. A single amino acid change in the V3 region of gp120 was sufficient to cause one isolate to switch from M-tropic to dual-tropic and acquire the ability to rapidly deplete all CD4+ T cells.     

Protein density and its influence on metabolite concentration and nitrogen retention by Holstein cows in late gestation

Multiparous Holstein cows in late gestation were used in a completely randomized design to test the effects of prepartum protein supply on prepartum N balance, blood metabolite and hormone concentrations, and postpartum intake and milk production. Cows were assigned to one of three isocaloric diets that differed in amount of total dietary crude protein (CP) (10.6, 12.7, or 14.5% of dry matter) but not in CP degradability or solubility. All diets contained the following ingredients: corn silage, chopped grass hay, ground corn, soybean meal, expeller soybean meal, minerals, and vitamins. Following parturition, all cows were offered a similar diet. Nitrogen balance was measured on d 12 to 7 prior to the expected calving date. Cows were bled on d 5 prior to the expected calving date from just prior to feeding to 8 h postfeeding. As dietary CP increased, plasma glucose concentrations increased linearly, but no change was detected in plasma nonesterified fatty acids or serum insulin concentrations. Nitrogen intake, apparent and true digestibilities, fecal and urinary concentration of and N balance increased as the concentration of dietary protein increased. The efficiency of absorbed protein utilization decreased as protein intake increased. No change in postpartum intake or milk production was observed. An increase in N retention in late gestation cows that were in positive N balance did not increase postpartum milk production.     

Children's use of looking behavior as a cue to detect another's goal

Three studies examined children's understanding of the role that looking behavior plays in revealing another's desired goal. In each study, participants were asked which of 2 objects a protagonist wanted to obtain. Four-year-olds did not infer that an object examined via prolonged looking was more likely to be the protagonist's goal than an object that was either glanced at or inadvertently touched. Instead, they were accurate only when the protagonist looked at one of two potential goals. In contrast, the majority of 6-year-olds (and adults in Experiment 1) consistently regarded prolonged looking as the more important cue of the protagonist's goal. These age differences suggest that development is characterized by an increasing appreciation that goal is revealed by comparative differences in the quality of perceptual connectedness to objects in the world. One explanation for these age differences is that preschoolers are limited in their understanding of the difference between perceiving with full attention and without it.     

Captopril modifies gene expression in hypertrophied and failing hearts of aged spontaneously hypertensive rats

The spontaneously hypertensive rat (SHR) exhibits a transition from stable compensated left ventricular (LV) hypertrophy to heart failure (HF) at a mean age of 21 months that is characterized by a decrease in alpha-myosin heavy chain (alpha-MHC) gene expression and increases in the expression of the atrial natriuretic factor (ANF), pro-alpha1(III) collagen, and transforming growth factor beta1 (TGF-beta1) genes. We tested the hypotheses that angiotensin-converting enzyme inhibition (ACEI) in SHR would prevent and reverse HF-associated changes in gene expression when administered prior to and after the onset of HF, respectively. We also investigated the effect of ACEI on circulating and cardiac components of the renin-angiotensin system. ACEI (captopril 2 g/L in the drinking water) was initiated at 12, 18, and 21 months of age in SHR without HF and in SHR with HF. Results were compared with those of age-matched normotensive Wistar-Kyoto (WKY) rats, and to untreated SHR with and without evidence of HF. ACEI initiated prior to failure prevented the changes in alpha-MHC, ANF, pro-alpha1(III) collagen, and TGF-beta1 gene expression that are associated with the transition to HF. ACEI initiated after the onset of HF lowered levels of TGF-beta1 mRNA by 50% (P<.05) and elevated levels of alpha-MHC mRNA two- to threefold (P<.05). Circulating levels of renin and angiotensin I were elevated four- to sixfold by ACEI, but surprisingly, plasma levels of angiotensin II were not reduced. ACEI increased LV renin mRNA levels in WKY and SHR by two- to threefold but did not influence LV levels of angiotensinogen mRNA. The results suggest that the anti-HF benefits of ACEI in SHR may be mediated, at least in part, by effects on the expression of specific genes, including those encoding alpha-MHC, ANF, TGF-beta1, pro-alpha1(III) collagen, and renin-angiotensin system components.     

Kinematic analysis of shear displacement as a means for operating mechanotransduction channels in the contact region between adjacent stereocilia of mammalian cochlear hair cells

In sensory hair cells of the cochlea, deflection of the stereociliary bundle results in direct mechanical gating of mechanoelectrical transduction channels, a function generally attributed to the tip link running between the tips of short stereocilia and the sides of adjacent taller ones. However, immunocytochemical experiments indicate that the channels may not be associated with the tip link but occur just below it in a region of contact between the stereocilia. To determine whether transduction channels in this location could be operated during physiologically appropriate deflections as effectively by shear displacement as if they were associated with the tip link, a two dimensional kinematic analysis of relative motion between stereocilia has been performed assuming contact between stereocilia is maintained during deflection. Bundle geometry and dimensions were determined from transmission electron micrographs of hair cells from several frequency locations between 0.27 and 13.00 kHz in the guinea-pig cochlea. The analysis indicates that for a 10 nm deflection of the tallest stereocilia of both inner and outer hair cells, i.e. within the range of the maximum sensitivity of mammalian hair bundles, the average shear displacement in the contact region would be 1.6 nm, but that it increases systematically towards higher frequency regions for outer hair cells. This displacement is comparable in magnitude to tip-link elongation for individual stereociliary pairs.