Biomedical subjects

Bruce E Miller

Publications and source records attributed to Bruce E Miller.

8 recordsLinked to original sources

PubMed2006

Failure of surface-modified bypass circuits to improve platelet function during pediatric cardiac surgery.

OBJECTIVE: Surface-modified cardiopulmonary bypass circuits have been shown to improve platelet function and decrease postoperative bleeding after heart surgery in adults. Two surface-modified cardiopulmonary bypass circuits are approved and commercially available for pediatric cardiac surgery. There have been few studies demonstrating the efficacy of these modifications for children. We performed a prospective, randomized trial comparing surface-modified cardiopulmonary bypass circuits to a standard unmodified circuit in pediatric cardiac surgery. METHODS: Sixty-nine children (median 6 months old) undergoing first-time cardiac surgery were enrolled and randomized to an uncoated circuit or one of the two commercially available surface modified circuits for their operation. Blood samples were collected at baseline, on cardiopulmonary bypass, at the end of rewarming, after protamine, and at 18 to 24 postoperative hours. Platelet count, beta-thromboglobulin, and thromboelastography with and without abciximab were measured. Postoperative chest tube outputs and blood product utilization were also analyzed. RESULTS: The platelet counts, beta-thromboglobulin levels, thromboelastographic measures of platelet function, and postoperative bleeding were not significantly different between the surface-modified cardiopulmonary bypass circuit groups and the control group. CONCLUSION: Currently available surface-modified cardiopulmonary bypass circuits do not significantly improve platelet function or clinical outcomes after routine pediatric cardiac surgery.

Blood Platelets↗

PubMed2006

Clinical measures of heparin's effect and thrombin inhibitor levels in pediatric patients with congenital heart disease.

In this investigation, we examined the relationship among three thrombin inhibitors, antithrombin III (ATIII), heparin cofactor II (HCII), and alpha-2-macroglobulin (alpha2M), and several clinical tests of heparin's effect in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass. One hundred eighteen children were stratified into six age groups: <1 mo, 1-3 mo, 3-6 mo, 6-12 mo, 12-24 mo, and >10 yr. Baseline ATIII, HCII, and alpha2M values were measured. Baseline celite- and kaolin-activated clotting times (ACT) were also measured and repeated 3 min after a standard heparin dose of 400 U/kg. Differences in ACT values before and after heparin administration and a heparin dose-response relationship were calculated for each patient. Kaolin-activated ACT tests showed less variation after heparin administration than celite-activated tests. In contrast to what has been demonstrated in adults, ATIII showed no positive correlation with the clinical tests of heparin's effect nor did the other thrombin inhibitors. Additionally, patients <1 mo old had unexpectedly low levels of alpha2M accompanying their expected low levels of ATIII and HCII. Our findings raise concerns about the ability of heparin to adequately anticoagulate these neonates during cardiopulmonary bypass and, consequently, challenge the accuracy of ACT prolongation to truly reflect the extent of their anticoagulation.

Antithrombins↗

PubMed2005

An evaluation of the effects of a standard heparin dose on thrombin inhibition during cardiopulmonary bypass in neonates.

We compared the adequacy of heparinization in neonates and older children undergoing cardiopulmonary bypass (CPB) by measuring heparin activity, thrombin formation, and thrombin activity. Ten neonates and 10 older children were administered 400 U/kg of heparin before CPB. Heparin anti-Xa activity, prothrombin fragment 1.2 (F1.2), and fibrinopeptide A (FPA) were measured at baseline, after 30 min on CPB, immediately post-CPB, and 3 and 24 h post-CPB. Heparin anti-Xa activity was significantly decreased during and immediately post-CPB in the neonatal group. F1.2 and FPA levels in neonates were significantly higher at baseline, decreased with the commencement of CPB, and increased to levels higher than those in older children after CPB. Our data show that with standard heparin doses, neonates exhibit less heparin anti-Xa activity during CPB. Higher baseline levels of F1.2 and FPA present in neonates indicate preoperative activation of their coagulation systems as compared with older children. Although F1.2 and FPA levels initially decrease with the commencement of CPB, probably representing hemodilution, the subsequent increase in these markers indicates significantly more thrombin formation and activity during and after CPB. These results raise the concern that 400 U/kg of heparin may not adequately suppress thrombin formation and activity in neonates undergoing CPB.

Adolescent↗

PubMed2005

Multiplexed cytokine sandwich immunoassays: clinical applications.

Flow cytometric, microsphere-based immunoassays have been developed for the simultaneous detection of soluble analytes in a variety of sample types. The ability to discriminate between individual microspheres on the basis of size, fluorescent intensity, and/or wavelength has allowed the simultaneous analysis of multiple analytes from the same sample. Cytokines are particularly good candidates for multiplexed analysis. Through intricate networks and complex feedback mechanisms, cytokines modulate each other as well as a multitude of cellular events and play an important role in health and disease. The simultaneous measurement of multiple cytokines in a single biological sample has tremendous potential value to further our understanding of the role of these immunomodulators in health and disease. This chapter describes a multiplexed, microsphere-based flow cytometric method to quantitate and compare multiple cytokines simultaneously in human serum. Serum poses a challenge for multiplexed cytokine analysis owing to the presence of numerous proteins and other potentially interfering factors. Assessment of the "real world" performance of the multiplexed, microsphere-based flow cytometry assay with clinically relevant sample types is critical for determining the proper application of these methods in deciphering the role of cytokines in disease pathogenesis and for evaluating drug action.

Cytokines↗

PubMed2004

Validation and comparative analysis of a multiplexed assay for the simultaneous quantitative measurement of Th1/Th2 cytokines in human serum and human peripheral blood mononuclear cell culture supernatants.

There is increasing evidence suggesting a relationship between cytokine levels and disease pathogenesis, which has led to interest in analyzing multiple cytokines in biological fluids and culture supernatants for various research and clinical studies. The introduction of methodologies allowing simultaneous measurement of interrelated biomarkers/cytokines has further revolutionized this process. In contrast to tissue culture supernatant, the measurement of cytokines in serum has proven to be difficult to characterize in multiplexed formats because of the presence of large dynamic concentration ranges of proteins and other interfering factors that are present in this matrix. In the present study, we have used the microsphere-based multiplex method to simultaneously quantitate and compare six analytes, encompassing a representation of the Th1/Th2 cytokine panel (interleukin (IL)-2, IL-4, IL-5, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and IL-10), in both serum and culture supernatants from peripheral blood mononuclear cells (PBMCs). A detailed validation procedure for these determinations is described along with a comparative analysis of the performance of the multiplexed assay in serum and culture supernatant matrices. Our results indicate that precision of the multiplexed assay is comparable in both culture supernatant and serum. However, the accuracy of quantification of cytokines in the serum matrix but not in culture supernatant may be compromised depending upon the cytokine being analyzed. Therefore, one must use caution when interpreting data from such complex matrices. Nevertheless, this assay format is appropriate to profile cytokines in clinical trial samples.

Cells, Cultured↗

PubMed2004

Fibrinogen in children undergoing cardiac surgery: is it effective?

There is speculation based on laboratory tests and biochemical data regarding the functional integrity of the fibrinogen in young children. Recent investigations in adults have demonstrated that their fibrinogen level correlates with the thromboelastogram maximum amplitude (MA) after modification with a glycoprotein IIb/IIIa receptor blocker that uncouples platelet-fibrinogen interactions. We postulate that if the fibrinogen of young children is functionally intact then their fibrinogen levels should also correlate with modified thromboelastogram MA values as they do in adults. We compared modified and unmodified thromboelastogram variables of 250 children <2 yr old undergoing cardiac surgery with their fibrinogen levels and platelet counts. Five age groups were distinguished to determine if and when correlations become significant (<1 mo, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo). Fibrinogen levels correlated with modified thromboelastogram MAs only in the 12-24 mo group. In this 12-24 mo age group other correlations between fibrinogen levels and thromboelastogram variables influenced by fibrinogen also became significant, as did correlations noted in adults between platelet counts and thromboelastogram variables. We conclude that the fibrinogen of children <12 mo old with congenital heart disease is qualitatively dysfunctional.

Abciximab↗

PubMed2003

Tissue factor-activated thromboelastograms in children undergoing cardiac surgery: baseline values and comparisons.

UNLABELLED: Activation of clotting with tissue factor (TF) allows rapid evaluation of thromboelastograms but alters the values of thromboelastogram variables. We have performed TF-activated thromboelastograms in 250 children <2 yr old undergoing cardiac surgery to establish baseline values. Five groups were distinguished to evaluate the effects of quantitative deficiencies in coagulation factor levels during infancy: <30 days, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo. Activation of clotting (R and K values) was similar among groups. Infants 1-3 mo of age demonstrated increased clot strength compared with the other groups, a finding similar to previous evaluation of native thromboelastograms. The alpha and maximum amplitude values were numerically almost identical in each age group, a unique finding in activated thromboelastograms. Fibrinolysis was similar among groups. We believe that knowledge of baseline TF-activated thromboelastogram variables in young children will be useful in interpreting these thromboelastograms in clinical scenarios, in using these thromboelastograms as part of coagulopathy treatment algorithms, and during the application of more specific thromboelastogram modifiers. Additionally, the similarity of alpha and maximum amplitude values in each age group will allow even faster interpretation of thromboelastogram data. IMPLICATIONS: Baseline values for tissue factor-activated thromboelastograms in young children undergoing cardiac surgery have been established and will permit accurate use and interpretation of this thromboelastogram modification in evaluating and managing coagulopathies.

Algorithms↗

PubMed2002

Anesthetic and perfusion issues in contemporary pediatric cardiac surgery.

As the fields of pediatric cardiology and cardiac surgery advance in complexity and in accountability for clinical and economic outcomes, several issues traditionally associated with the operating room are becoming important to physicians, nurses, and respiratory therapists who take care of children after cardiac surgery. The article discusses the concepts of "fast track" cardiac surgery, regional anesthetic techniques, coagulopathies and bleeding after cardiopulmonary bypass, intraoperative ultrafiltration, and mechanical circulatory assist devices.

Anesthesia↗