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K Ault

Publications and source records attributed to K Ault.

29 records · Page 2Linked to original sources
PubMed1994

Platelet Activation Determined by Flow Cytometry Persists Despite Antithrombotic Therapy in Patients with Unstable Angina and Non-Q-Wave Myocardial Infarction.

Background: Current strategies in the treatment of patients with acute coronary syndromes include antiplatelet agents and thrombin antagonists, most commonly aspirin and heparin, respectively. Cardiac events, however, occur despite what is considered to be maximal medical treatment. Methods: We determined the percentage of activated platelets in whole blood samples taken from 22 patients with unstable angina and non-Q-wave myocardial infarection participating in the TIMI III B trial. Platelet activation was assessed using a monoclonal antibody to the surface-expressed alpha-granule protein, P-selectin, and flow cytometry. All patients received a full complement of antiischemic medications as well as intravenous heparin and oral aspirin, and were then randomized to tissue plasminogen activator or placebo. Results: Platelet activation prior to randomization was increased threefold to fourfold compared with healthy volunteers (11.4 +/- 11.4% vs. 2.0%; p < 0.01). Serial measurements performed 12, 24, 48, and 96 hours after treatment initiation revealed that platelet activation persisted. No differences in patients experiencing recurrent ischomic events (n = 9) or those randomized to a 90-minute, accelerated infusion of tissue plasminogen activator (n = 12) were observed. Conclusions: A modest degree of platelet activation is seen for at least 96 hours and possibly longer in patients with unstable angina and non-Q-wave myocardial infarction, despite being treated with intravenous heparin and oral aspirin. These findings support current efforts to identify more potent and selective antithrombotic treatment strategies.

Journal Article↗
PubMed1994

The clinical use of flow cytometry for assessing platelet activation in acute coronary syndromes. TIMI-III Thrombosis and Anticoagulation Group.

BACKGROUND: Unstable angina signals a sudden transition from stable to unstable atherosclerotic coronary artery disease. Although assessment of platelet activity has been shown to provide diagnostic and prognostic information, most available methods lack sufficient sensitivity or specificity for them to be useful in clinical practice. In recent years, fluorescently labeled antibodies and flow cytometry have permitted the detection of activation proteins on individual platelets. The purpose of the present study was to assess the ability of flow cytometry to detect platelet activation in patients with unstable angina and non-Q-wave myocardial infarction. METHODS: Platelet activation before treatment was determined from whole-blood samples in 19 patients participating in the Thrombolysis in Myocardial Ischemia (TIMI)-IIIB study and in nine healthy volunteers (total of 24 samples) using flow cytometry and a monoclonal antibody (clone 1E3) to the activation-dependent, surface-expressed protein P-Selectin. RESULTS: Among healthy volunteers, a small percentage of platelets were activated (2.0 +/- 2.5%). In contrast, 15 out of 19 (79%) patients with suspected myocardial ischemia at rest had 10.4 +/- 11.1% activated platelets (95% confidence interval 4.9-15.9%; P < 0.01). Seven patients (37%) were found to have more than 10% activated platelets. The degree of platelet activation did not differ significantly between patients with unstable angina and those with elevated creatine kinase levels (non-Q-wave myocardial infarction). CONCLUSION: Whole-blood flow cytometric techniques can minimize the artifactual platelet activation often seen with other techniques and therefore offer distinct advantages in the investigation of patients with thrombotic coronary syndromes. In TIMI-III, patients with unstable angina and non-Q-wave myocardial infarction had clear evidence of platelet activation. An ongoing study will examine the correlation between platelet activation assessed using flow cytometry and clinical events in a larger patient cohort.

Acute Disease↗
PubMed1992

Stable isotope model for estimating colonic acetate production in premature infants.

In premature infants, a nutritionally significant proportion of lactose is apparently fermented in the colon to acetate. To estimate the rate of entry of acetate into the peripheral circulation, a model that takes into account extraction of gut-derived acetate by splanchnic and hepatic tissues was developed. Using a [1-13C]acetate orogastric infusion technique, six studies were carried out on five premature infants during constant orogastric feeding. Ranges in gestational age, postnatal age, and breath H2 concentration (corrected for CO2 content) were 28-32 weeks, 16-29 days, and 45-252 microL/L, respectively. The estimated rate of entry of acetic acid (mean +/- SD) was 63.7 +/- 33.8 mumol.kg-1.min-1 (range, 22.9-123.2 mumol.kg-1.min-1), which corresponded to 64.3% +/- 38.6% (24%-136%) of the potential two carbon units from dietary lactose. Thus, a substantial fraction of dietary lactose in premature infants may be converted to acetic acid; this conversion could have a significant effect on protein as well as energy requirements.

Acetates↗
PubMed1992

In vivo estimation of lactose hydrolysis in premature infants using a dual stable tracer technique.

To investigate their putative capacity for lactose digestion, primed continuous orogastric infusions of [1-13C]glucose and D-[1-13C]lactose were administered on consecutive days to five premature infants (30-31 wk gestation, 15-32 days of age), who were fed by orogastric infusions of human milk or formula. By monitoring the plateau isotopic enrichment of plasma glucose using isotopomers containing the entire derivatized glucose molecule or C-2 through C-6, we were able to distinguish label appearing in the peripheral circulation deriving from unmetabolized glucose from that arising from recycled or fermented glucose (or lactose). Isotopic enrichment of the C-1 of glucose, corrected for recycling, was then calculated during each tracer infusion, and the fraction of dietary lactose subjected to in vivo hydrolysis was estimated from these values and the respective tracer infusion rates, assuming similar absorptive and metabolic fates of labeled glucose arising from either tracer. This fraction averaged 1.02 +/- 0.16 (SD), suggesting that lactose digestion is efficient by 34-wk postconceptional age.

Bicarbonates↗
PubMed1991

Platelet activation and aggregation during cardiopulmonary bypass.

Increases in plasma concentrations of platelet granule products such as platelet factor 4 and beta-thromboglobulin during cardiopulmonary bypass suggest that platelets are activated during extracorporeal circulation. Subsequent circulation of these activated platelets may be responsible for the ubiquitous platelet dysfunction associated with cardiopulmonary bypass. Using flow cytometry and a monoclonal antibody directed against an alpha-granule membrane protein, granule membrane protein 140 (GMP-140), which is expressed on the platelet surface membrane after activation, we directly measured the percentage of circulating activated platelets in 41 patients before, during, and after cardiopulmonary bypass. In addition, we compared the GMP-140 expression with platelet aggregation in response to adenosine diphosphate (ADP). Cardiopulmonary bypass produced a significant increase in the percentage of GMP-140-positive platelets persisting in the circulation; the percentage peaked at a mean of 29% (range 10-58%) before separation from extracorporeal circulation. A significant percentage of these activated platelets continued to circulate in the early postoperative period. Simultaneous measurement of platelet aggregation in response to ADP demonstrated an aggregation defect that had a time course distinct from platelet activation and whose magnitude did not correlate with the degree of platelet activation in individual patients. We conclude that cardiopulmonary bypass causes a complex constellation of platelet defects, which include alpha-granule release, prolonged circulation of activated, "spent" platelets, and impaired platelet aggregation.

Adenosine Diphosphate↗
PubMed1984

Heparin inhibition of antibody-dependent complement-mediated lysis.

The effect of heparin on the monoclonal antibody-dependent complement-mediated lysis of human lymphoid cell lines and peripheral blood T-lymphocytes was studied. T-lymphoid cell lines (CEM and MOLT-3) were lysed by optimal concentrations of monoclonal antibodies and rabbit complement. Heparin at concentrations as low as 0.5 U/ml partially inhibited the complement-mediated lysis of all antibody-cell combinations while a heparin concentration of 25 U/ml produced complete inhibition. Lysis mediated by an IgG monoclonal antibody (J5) to the common acute lymphoblastic leukemia antigen (CALLA) was more sensitive to heparin inhibition than that due to an IgM antibody (VIL A1). Bovine and porcine heparin were equally inhibitory. Peripheral blood T-lymphocytes collected in heparin (100 U/ml) were resistant to complete lysis when treated with 17F12 and complement immediately after isolation; complete lysis was achieved only when they were incubated for 2 h prior to treatment. The role of monoclonal antibody and complement in the in vitro lysis of normal and leukemic lymphocytes is discussed.

Animals↗
PubMed1980

Regulation of monoclonal immunoglobulin G synthesis by antiidiotypic antibody in a patient with hypogammaglobulinemia.

The regulation of in vitro antibody synthesis by antiidiotypic antibodies was studied in a child with hypogammaglobulinemia and a serum immunoglobulin (Ig)G1 kappa M component. A rabbit antiserum was raised against the purified M component and was rendered idiotype specific by extensive absorption with Cohn fraction II and with IgG derived from the patient's parents. Hemagglutination-inhibition studies demonstrated that less than 1 in 300,000 molecules of pooled human IgG carried M component-related idiotypic determinants. 12% of the patient's B cells, but none of her T cells, expressed idiotypic determinants on their surface. Spontaneous de novo synthesis of the M component by the patient's peripheral blood lymphocytes was demonstrated in vitro and was shown to proceed independently of the polyclonal activator pokeweed mitogen. Antiidiotypic rabbit IgG, but not its F(ab')2, fragments, profoundly inhibited the synthesis of M component by the patient's peripheral blood lymphocytes. We concluded that antiidiotypic antibodies may play a role in the regulation of antibody synthesis in man.

Agammaglobulinemia↗
PubMed1976

Effects of training on biochemical values in standardbred horses.

Effects of training at a regular, fixed, standard exercise load on venous lactic acid, mixed venous and arterial blood gases and pH, and serum muscle enzymes were determined on previously unconditioned, healthy, adult, Standardbred horses. Arterial and mixed venous blood gases, pH, and serum muscle enzymes did not change in a consistent manner during training. Venous lactic acid concentrations did increase significantly with training and may be of value for the biochemical evaluation of fitness in horses.

Animals↗
PubMedDate not supplied

Flow cytometry: its applications in hematology.

The techniques of flow cytometry are becoming more and more important for the clinical hematology laboratory. No longer a novelty confined to a few specialized institutions as it was 10 years ago, flow cytometry has blossomed into a mature discipline. The methodology is well-known, the mechanical apparatus is readily available, and the role it plays in clinical hematology is increasingly appreciated. The burgeoning number of scientific articles devoted to this topic attests to the interest it has aroused as a tool for both medical research and patient care. In fact, more than a thousand such papers are now published each year and it would be impossible to deal with all the methodologies and applications of FCM currently utilized or under development. Throughout this paper four relevant hematologic fields are briefly discussed, in which FCM appears to be of great help at present: the immunophenotyping of leukemias and lymphomas, the measurement of proliferative activity and DNA ploidy in hematological malignancies, the detection of drug resistant leukemic cells and the use of FCM in the study of platelets.

Flow Cytometry↗