Proposed changes in the Medicare reimbursement method for end-stage renal disease (ESRD) patients prompted us to study the total cost of caring for the ESRD patients in northeast Indiana over a 1-year period. We hoped to ascertain the actual cost of caring for patients treated with different modalities, determine if we could compete in a capitated environment, and identify areas in which we might reduce these expenses. Six patients new to dialysis and 29 patients already receiving treatment underwent follow-up evaluation for 1 year. We tracked their cost of care for 1 year in the outpatient setting as well as in the hospital. We found the cost of caring for all patients was $43,044 per year. Patients new to dialysis cost $3,164 more to care for than patients already receiving dialysis treatment. Hospitalization expense was the primary component of that difference. Continuous ambulatory peritoneal dialysis (CAPD) patients were $14,570 less costly per year to care for than hemodialysis patients. This differential primarily related to decreased hospitalization. Vascular access expenses were a major component of both the outpatient and inpatient cost for hemodialysis patients. Our yearly expenditures for all patients compared with suggested capitated Medicare reimbursement rates suggested that our program could be successful in a new reimbursement model. Several areas of possible cost reduction were identified.

Aged↗

PubMed1997

The assessment of acute confusion as part of nursing care.

Older adults who become acutely confused when hospitalized present challenges to nurses because of their increased care needs and risk for injury. This study evaluated the feasibility of introducing the NEECHAM Confusion Scale as part of usual nursing care as a first step in improving nurses' ability to assess, prevent, and manage acute confusion in hospitalized older adults. By addressing several of the factors that influence adoption and continuation of a new practice, this study found that staff nurses could successfully use the NEECHAM Confusion Scale.

Acute Disease↗

PubMed1997

Unexpected augmentation of mycophenolic acid pharmacokinetics in renal transplant patients receiving tacrolimus and mycophenolate mofetil in combination therapy, and analogous in vitro findings.

Mycophenolate mofetil (MMF) a potent immunosuppressive agent, has recently been approved for clinical use (CellCept) in renal transplant patients in combination with cyclosporine (CsA). With the expanded use of tacrolimus (Prograf) as well in renal transplant patients, there is a lack of pharmacokinetic studies clarifying drug interactions between the three agents. A pharmacokinetic study was performed on 18 stable renal transplant patients receiving MMF and tacrolimus together, and four control groups, one receiving tacrolimus alone, two receiving CsA, in combination with MMF (1.0 or 1.5 g bid), and one receiving CsA microemulsion (Neoral). Area-under-the-curve values were calculated for each drug to assess if there was a reciprocal effect on the respective bioavailability of each. In vitro, the immunosuppressive effect of trough level plasma from each patient group was studied using mixed lymphocyte culture (MLC), as well as MLC reactions spiked with various combinations of each drug. There was a minimal effect of MMF on tacrolimus pharmacokinetics. However, patients receiving tacrolimus and MMF displayed significantly higher levels (Cmin and area under the curve) of mycophenolic acid (MPA) than those receiving CsA (Sandimmune or Neoral) and the same dose of MMF (50.2 +/- 16.5 vs 32.1 +/- 16.7 micrograms h/ml AUC, p < 0.02). Equivalent MPA levels could be attained in patients receiving CsA if the MMF dose was increased by 50% (1.5 g bid). There were also significantly lower levels of the glucuronide metabolite of MPA (MPAG) (755 +/- 280 vs 1230 +/- 250 micrograms h/ml AUC, p = 0.02), suggesting a specific inhibition (either direct or indirect) of the conversion of MPA to MPAG in tacrolimus patients, as opposed to those receiving CsA. For each drug combination, there was a positive correlation between the plasma immunosuppressive effect seen in MLC assays and the MMF dose. In addition, trough plasma from patients receiving tacrolimus and MMF was significantly more MLC inhibitory than from those receiving CsA or CsA microemulsion and equivalent-dose MMF. Culture media containing MPA and tacrolimus equal to clinical therapeutic trough concentrations (10 ng/ml) were significantly more MLC inhibitory than CsA at equivalent clinical therapeutic trough concentrations (200 ng/ml) with equivalent MPA levels. These studies in renal transplant patients suggest that tacrolimus in combination with MMF may result in a greater degree of immunosuppression than may be anticipated.

Adult↗

PubMed1997

Dipeptidyl peptidase IV (CD26) activity in human alloreactive T cell subsets varies with the stage of differentiation and activation status.

Dipeptidyl peptidase IV (DPP IV), also known as CD26, is a transmembrane serine aminopeptidase which has an ontogenically related expression on T cells and participates on several immunological functions. CD26 appears to play an important role in alloimmunity during host T cell activation subsequent to alloantigen encounter and is a way by which effector T cells traverse graft endothelial barriers. In order to help to elucidate the role of the CD26 molecule in alloimmune responses, DPP IV activity and CD26 antigenic expression were assessed during the initial phases of completely MHC-disparate human mixed lymphocyte reactions (MLRs) and in several long-term alloreactive T cell clones. Our methods involved the use of a rhodamine-110-conjugated dipeptide substrate specific for DPP IV in two-colour cytofluorographic analysis that allowed stimultaneous lineage marker evaluation. Polyclonal populations of alloreactive CD4 and CD8 T cells contained DPP IV activity at 1 and 10 min of incubation that was variably elevated from resting T cells with the enzyme activity confined to CD26+ cells. T cell clones derived from MLRs were established with IL-2 supplementation and alloantigen restimulation and had reduced CD62L expression with functional specificity to the stimulating MHC. While CD26 expression remained stable, DPP IV activity was variable in the alloreactive T cell clones, with enzyme function in the latter appearing to coincide with the timing of alloantigen restimulation. These studies demonstrate that DPP IV activity varies among phenotypically distinct alloreactive T cell subsets and appears to be altered with the activation status of the effector cells. These findings raise the potential of a role for CD26/DPP IV in the generation of specific alloimmunity. With this methodology, it may be possible to reveal whether specific alterations in the activity of this molecule in T cell populations promote graft acceptance and to determine the molecular requirements for these changes.

CD4-Positive T-Lymphocytes↗

PubMed1997

Endosomal proteases and antigen processing.

T cells are activated by fragments of antigenic proteins bound to major histocompatibility complex (MHC) molecules and displayed on the cell surface. MHC class II proteins scavenge processed protein antigens from within endosomal compartments. The antigenic peptides are generated within these and other intracellular compartments using the array of proteolytic enzymes normally involved in terminal protein degradation. Antigen-presenting cells use different mechanisms to exploit and control the activity of these enzymes so as to ensure the generation of a wide variety of peptides, while preventing the destruction of antigenic epitopes by excessive proteolysis.

Antigen Presentation↗

PubMed1997

The immune reactivity role of HCV-induced liver infiltrating lymphocytes in hepatocellular damage.

Liver infiltrating lymphocytes (LIL) were isolated from HCV-positive (+) and HCV-negative (-) end-stage livers. Phenotypic analysis and functional studies using proliferative and lymphocytotoxic assays were performed with the isolated LIL. Two CD3+ lymphocyte populations were found in LIL using FITC anti-CD3 monoclonal antibodies (mAb). One was a bright fluorescence intensity population (as in PBL), and the other dim. We calculated the number of FITC-anti-CD3 mAbs bound per lymphocyte on PBL and LIL and found 80,040 +/- 4628 and 39,615 +/- 3932, respectively. Therefore, HCV+ and HCV- patient PBL contained approximately twice the number of CD3 molecules per cell than patient CD3+ LIL. LIL also contained approximately a threefold higher concentration of TCR alpha beta +, CD4-CD8-, and CD56,16 (NK) cells than the patient PBL. Thus, a major subset of LIL is phenotypically similar to mouse NK1.1+ "intermediate" T cells. LIL freshly isolated from HCV+ livers exhibited weak CTL activity against EBV- or Con A-transformed lymphoblast targets infected with vaccinia-HCV recombinant virus (rHCV) or primary hepatocyte cultured cells. However, after in vitro coculture of LIL with rHCV, these cells developed a strong cytotoxicity for the above targets. In contrast, LIL from HCV- livers were not cytotoxic against the same targets. Histochemical studies (in situ) demonstrated that these hepatocytes express CD95, and stains demonstrated apoptosis. The HCV+ hepatocytes also express class I MHC molecules and ICAM-1. The addition of mAb specific for these adhesion molecules inhibited CML activity. Short-term cultured hepatocytes (targets) from HCV+ and HCV- patients produced low levels of cytokines IL-1 beta, IL-2, IL-6, TNF alpha, and IFN-gamma but a high level of IL-8. It is speculated that LIL expressing reduced numbers of CD3 molecules may even function as immune regulators as proposed for intermediate T cells in mice.

Antibodies, Monoclonal↗

PubMed1997

Mental rotation interferes with response preparation.

Reaction times (RTs) and lateralized readiness potentials (LRPs) were studied to find out whether response preparation begins after mental rotation finishes, as assumed by discrete-stage models. Stimuli were disoriented normal or mirror-image characters, with character name determining which hand would respond. In Experiment 1, the normal/mirror-image information determined whether the response was to be executed (go) or withheld (no-go), and LRPs indicated that responses were weakly prepared before the end of mental rotation. Mental rotation was not required in Experiment 2, and significantly more response preparation was observed. In Experiment 3, probe RT trials embedded in the mental rotation task indicated that hand information is available to the response preparation process during rotation. Apparently, some response preparation occurs before mental rotation finishes, but rotation interferes with response preparation.

Adolescent↗

PubMed1997

Interferon-induced growth arrest is mediated by membrane structural changes.

Interferon-gamma (IFN-gamma) is an immunomodulator shown to augment the expression of major histocompatibility (MHC) class I/class II antigens on the cell surface. In previous studies, we have demonstrated that the enhanced expression of these antigens on the cell surface is in part due to IFN-gamma-mediated abrogation of antigen shedding. In this study, we demonstrate that IFN-gamma induces structural changes in the cell membrane by altering the cholesterol/phospholipid ratio. Furthermore, such changes not only mediate enhanced expression of antigen on the cell surface but may drive the cells to growth arrest and apoptosis. These results were obtained by employing x-ray diffraction, electron microscopy, and DNA analysis.

Adjuvants, Immunologic↗

PubMed1997

Effects of crystalloid solutions on circulating lactate concentrations: Part 1. Implications for the proper handling of blood specimens obtained from critically ill patients.

OBJECTIVES: a) To test the hypothesis that circulating lactate concentrations are the same in simultaneously collected arterial and central venous blood specimens; b) to test the hypothesis that even small amounts of crystalloid solutions, which are inadequately "cleared" from these indwelling arterial and venous catheters, can lead to clinically important and misleading changes in the measured lactate values. DESIGN: A prospective, multiexperiment study. SETTING: A critical care research laboratory and a 20-bed intensive care unit (ICU). PATIENTS: Three hundred fifty-five patients. INTERVENTIONS: Blood samples were collected. MEASUREMENTS AND MAIN RESULTS: Experiment 1: Simultaneously collected arterial and central venous blood specimens were obtained on 148 occasions from 48 medical ICU patients receiving no lactated Ringer's solution (RL). Arterial and central venous lactate values were nearly identical in these patients. The correlation between the arterial and central venous lactate concentrations was excellent (r2 = .85; p < .0001) and the agreement between the arterial and central venous lactate concentrations was also excellent (bias and precision = 0.04 mmol/L and +/- 0.38 mmol/L, respectively). Experiment 2: Arterial and mixed venous blood samples were obtained from 100 percutaneous transluminal coronary angioplasty (PTCA) and 75 cardiac surgical patients immediately before the performance of these cardiac procedures. We found the central venous lactate concentrations to be higher than arterial lactate values in the cardiac surgical group, and there was a very poor correlation (r2 = .07) between arterial and central venous lactate values in the cardiac surgical group. The correlation between central venous and arterial lactate concentrations in the PTCA patients was excellent (r2 = .84) and similar to the findings of experiment 1. Since the cardiac surgical patients received RL and the PTCA patients received no RL, we speculated that the intravenous infusion of RL in the cardiac surgical group accounted for these discordant findings. To test this speculation, we performed experiments 3 and 4. Experiment 3: In a large bench study, blood specimens were divided into multiple 1-mL aliquot portions, to which 0.01, 0.05, 0.10, 0.50, or 1.0 mL of various crystalloid solutions, containing or not containing RL, were added. In a volume-dependent and linear manner, solutions containing RL increased the circulating lactate concentration from 10% to > 400% of the baseline lactate value. In a volume-dependent and linear fashion, the non-RL crystalloid solutions decreased the lactate concentration by 0 to 66% of the baseline nondiluted lactate concentration. Experiment 4: In 30 different cardiac surgical patients, we simultaneously obtained central venous and arterial blood specimens. Patients this time received no RL, and catheter lines were adequately cleared (removal > 5 mL) of crystalloid solutions. We found a correlation (r2 = .82; p < .0001) that was virtually identical to the findings of experiment 1 and to the findings in the PTCA group of experiment 2. CONCLUSIONS: a) Arterial and central venous lactate concentrations are similar in hemodynamically stable critically ill patients, b) Even small amounts of RL-containing solutions in catheters used for blood sampling may cause false increases in the circulating lactate concentration. c) Even small amounts of non-RL crystalloid solutions in catheters used for blood sampling may falsely decrease circulating lactate values. d) When blood specimens are drawn from indwelling catheters, all crystalloid solutions must be cleared from the line.

Blood Specimen Collection↗

PubMed1997

Effect of intravenous lactated Ringer's solution infusion on the circulating lactate concentration: Part 3. Results of a prospective, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: We previously discovered that small amounts of lactated Ringer's solution, which are inadequately cleared from an intravenous catheter, falsely increase the circulating lactate concentration in blood samples collected from that catheter. That finding prompted us to test the hypothesis that intravenous lactated Ringer's solution, infused at a rate used in resuscitation, would increase the circulating lactate concentration. DESIGN: A prospective, randomized, double-blinded, placebo-controlled study. SETTING: A critical care research laboratory. SUBJECTS: Twenty-four normal, healthy, adult volunteer subjects. INTERVENTIONS: Two intravenous catheters were placed. One was used for the infusion of the test solution and the other catheter was used for blood sampling. Blood samples were serially collected for the determination of blood lactate concentrations. MEASUREMENTS AND MAIN RESULTS: Twenty-four healthy adult volunteers were randomized to receive a 1-hr infusion of either lactated Ringer's solution (n = 6), 0.9% saline (n = 6), 5% dextrose in lactated Ringer's solution (D5RL) (n = 6), or 5% dextrose in water (D5W) (n = 6). Each subject received nothing by mouth after midnight. At 0800 hrs, catheters were inserted and each subject received 1 L of the assigned solution over 1 hr. Throughout the study, the subjects were at rest. Three-milliliter samples of venous blood were collected before, during (at 15, 30, 45, and 60 mins), and after (at 90, 120, and 240 mins) the infusion. Blood samples were placed on ice immediately after collection and analyzed within 5 mins of collection. Lactate concentrations were determined using an ion-selective, amperometric electrode, which we have previously validated. Lactate concentrations were compared between subjects receiving lactated Ringer's solution vs. subjects receiving normal saline. A similar comparison was made between subjects receiving D5RL vs. D5W at similar time points during the study. There were no clinically or statistically significant differences in lactate values at the time points studied in those subjects receiving lactated Ringer's solution vs. those persons receiving normal saline (p > .05; n = 12; Student-Newman-Keuls' multiple comparison test) or those subjects receiving D5W vs. those subjects infused with D5RL (p > .05; n = 12; Student-Newman-Keuls' multiple comparison test). In no case did the circulating lactate values exceed 2 mmol/L (the upper limit of normal). CONCLUSIONS: The short-term infusion of lactated Ringer's solution in normal adults (hemodynamically stable) does not falsely increase circulating lactate concentrations when 1 L is given over 1 hr. Therefore, clinicians should not disregard increased lactate concentrations in patients receiving a rapid infusion of lactated Ringer's solution.

Adult↗

PubMed1997

Heavy fragment production cross sections from 1.05 GeV/nucleon 56Fe in C, Al, Cu, Pb, and CH2 targets.

We have obtained charge-changing cross sections and partial cross sections for fragmentation of 1.05 GeV/nucleon Fe projectiles incident on H, C, Al, Cu, and Pb nuclei. The energy region covered by this experiment is critical for an understanding of galactic cosmic ray propagation and space radiation biophysics. Surviving primary beam particles and fragments with charges from 12 to 25 produced within a forward cone of half-angle 61 mrad were detected using a silicon detector telescope to identify their charge and the cross sections were calculated after correction of the measured yields for finite target thickness effects. The cross sections are compared to model calculations and to previous measurements. Cross sections for the production of fragments with even-numbered nuclear charges are seen to be enhanced in almost all cases.

Aluminum↗