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Biomedical subjects

J D Olson

Publications and source records attributed to J D Olson.

At least 19 recordsLinked to original sources

Long-term outcome of low-grade oligodendroglioma and mixed glioma.

BACKGROUND: Low-grade oligodendrogliomas and mixed gliomas can be indolent and remain unchanged for years. Optimal timing and effectiveness of initial treatment is uncertain and therapy can be associated with toxicity. METHODS: Retrospective review of patients diagnosed between 1979 and 1997 with low-grade oligodendroglioma or mixed glioma. Time to progression, survival, prognostic factors, and treatment toxicities were evaluated. RESULTS: A total of 106 patients (77 oligodendroglioma, 29 mixed glioma) were identified; median age was 36.7 years. Initial presenting symptoms were seizures in 76 (72%) and headache in 11 (10%); tumor was diagnosed as an incidental finding in five patients. Tumor progression was diagnosed in 72 patients (68%). Overall median time to progression (MTTP) was 5.0 years (range 0.5 to 14.2). Median overall survival (OS) was 16.7 years. No prognostic factors reached statistical significance. MTTP and OS were not significantly affected by treatment. Of 62 patients who received radiation therapy, 9 (15%) developed radiation necrosis and 13 developed radiation therapy-related cognitive changes, requiring ventriculoperitoneal shunting in six. Significant myelosuppression was seen in 35 of 76 (46%) patients treated with chemotherapy. CONCLUSIONS: Low-grade oligodendroglioma and mixed glioma have a long median overall survival. There were no apparent differences in either immediate versus deferred treatment or choice of initial therapy on disease-free or overall survival. Chemotherapy was associated with significant acute toxicity in almost one half of patients; radiation therapy produced late neurotoxicity in one third, justifying deferred treatment until clinically necessary.

Adolescent↗

Inhibition of human platelet function by sulfatides.

Sulfatides are glycolipid constituents of human platelet cell membranes and have been shown to interact with platelet-binding proteins involved in hemostasis. Because little is known about the physiological role of sulfatides in platelet function, the effect of sulfatide on platelet adhesion, aggregation, release, and ristocetin-induced platelet agglutination (RIPA) was studied. These processes are inhibited when exogenous sulfatide is present in vitro. Inhibition of aggregation induced by collagen, thrombin, and ristocetin by sulfatide was dose dependent. Adenosine diphosphate-mediated adhesion and aggregation were not significantly affected by sulfatide, nor was serotonin- and epinephrine-mediated aggregation. Collagen mediate release of serotonin was reduced sulfatide. RIPA demonstrated dose-dependent inhibition in response to sulfatide. These results suggest that sulfatide may play a role in modulating platelet activation.

Adrenergic Agonists↗

Coexisting dysfibrinogenemia (gammaR275C) and factor V Leiden deficiency associated with thromboembolic disease (fibrinogen Cedar Rapids).

Fibrinogen Cedar Rapids is a heterozygous dysfibrinogenemia (gammaR275C) that was associated with thromboembolism during and following pregnancy in three second-generation family members who also were heterozygotic for factor V Leiden (V R506Q). Like other dysfibrinogenemias with substitutions at position 275 of the gamma-chain, fibrinogen Cedar Rapids is characterized by defective end-to-end intermolecular fibrinogen and fibrin 'D : D' associations, a fibrin network structure that is composed of thicker and more highly branched fibers, normal fibrin 'D: E' associations, and normal factor XIII-mediated crosslinking of fibrinogen and fibrin. In addition, Cedar Rapids fibrinogen and fibrin displayed delayed plasmin lysis rates. Compared with normal fibrinogen, platelet aggregation or platelet fibrinogen receptor clustering was defective in the presence of fibrinogen Cedar Rapids. Most subjects with gammaR275 mutations do not experience clinical thrombotic disorders, suggesting that the combination of a factor V Leiden defect and a gammaR275C dysfibrinogenemia predisposes to thromboembolic disease.

Adult↗

Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice.

The adapter protein SLP-76 is expressed in T lymphocytes and hematopoietic cells of the myeloid lineage, and is known to be a substrate of the protein tyrosine kinases that are activated after ligation of the T-cell antigen receptor. Transient overexpression of SLP-76 in a T-cell line potentiates transcriptional activation after T-cell receptor ligation, while loss of SLP-76 expression abrogates several T-cell receptor-dependent signaling pathways. Mutant mice that lack SLP-76 manifest a severe block at an early stage of thymocyte development, implicating SLP-76 in signaling events that promote thymocyte maturation. While it is clear that SLP-76 plays a key role in development and activation of T lymphocytes, relatively little is understood regarding its role in transducing signals initiated after receptor ligation in other hematopoietic cell types. In this report, we describe fetal hemorrhage and perinatal mortality in SLP-76-deficient mice. Although megakaryocyte and platelet development proceeds normally in the absence of SLP-76, collagen-induced platelet aggregation and granule release is markedly impaired. Furthermore, treatment of SLP-76-deficient platelets with collagen fails to elicit tyrosine phosphorylation of phospholipase C-gamma2 (PLC-gamma2), suggesting that SLP-76 functions upstream of PLC-gamma2 activation. These data provide one potential mechanism for the fetal hemorrhage observed in SLP-76-deficient mice and reveal that SLP-76 expression is required for optimal receptor-mediated signal transduction in platelets as well as T lymphocytes.

Adaptor Proteins, Signal Transducing↗

A method for proficiency testing of small peer groups in the College of American Pathologists Coagulation Surveys.

OBJECTIVE: To develop a grading scheme for the proficiency testing of small peer groups of fewer than 10 members for the prothrombin time (PT) and activated partial thromboplastin time (APTT). METHODS: A modified target value for small peer groups was derived based on the assumption that measurement variability in the PT and APTT is more greatly influenced by variations in reagents than in instruments. Criteria for grading were established by statistical simulation to achieve misclassification errors of less than 5% for both incorrectly passing and failing participants. College of American Pathologists Coagulation Survey data were analyzed to determine the number of additional laboratories graded using the proposed scheme, as well as the failure rates among participants in the small peer groups. RESULTS: The modified target value for small peer groups is a weighted average between the mean of the peer group and the mean of all participants using the same reagent (reagent group). Peer groups with as few as 4 members can be graded provided that specific criteria are satisfied: there must be at least 5 peer groups for the same reagent, at least 3 of these 5 peer groups must have more than 3 members, and the coefficient of variation for the reagent group must be less than 10%. This proposed grading scheme decreased the number of ungraded laboratories by 44% to 46% for the PT and 42% to 55% for the APTT. The percentage of failing grades among participants in the small peer groups ranged from 1.3% to 4.1% for the PT and 1.4% to 7.2% for the APTT. These failure rates were 2.8- to 13.0-fold higher than the failure rates in large peer groups (P < or = .05). CONCLUSIONS: The proposed small peer group grading scheme can improve the effectiveness of College of American Pathologists proficiency testing for the PT and APTT and may also be generally applicable to other test methods and analytes.

Anticoagulants↗

The specific hospital significantly affects red cell and component transfusion practice in coronary artery bypass graft surgery: a study of five hospitals.

BACKGROUND: Interhospital differences in blood transfusion practice during coronary artery bypass graft (CABG) surgery have been noted, but the underlying issues have not been identified. STUDY DESIGN AND METHODS: Records of 3217 consecutive CABG cases in five university teaching hospitals in 1992 and 1993 were stratified by hospital, type of revascularization conduit, patients' sex, and other factors. Statistical methods were used to compare patient characteristics, transfusion outcomes, and hospital outcomes. RESULTS: Forward two-step logistic regression using patient likelihood of red cell transfusion factors in the first step and the specific hospital in the second step revealed a significant effect of hospital on the delta odds ratios for red cell transfusion. This finding was confirmed by analyses of a highly stratified subset of cases, males in diagnosis-related group 107 (primary cases of coronary bypass without coronary catheterization) who underwent revascularization with venous and internal mammary artery grafts, revealing variations among hospitals from 109 to 457 units of red cells transfused per hundred cases. Corresponding variations in transfusions of all blood components were from 324 to 1019 units by hospital. Variation in red cell transfusion practice among surgeons in the same hospital was not responsible for these interhospital differences. CONCLUSION: The effect of the specific hospital on transfusion practice is attributed to institutional differences that, through reasons of training or hierarchy, become ingrained in hospitals.

Aged↗

The Collaborative Hospital Transfusion Study: variations in use of autologous blood account for hospital differences in red cell use during primary hip and knee surgery.

BACKGROUND: Red cell use in patients undergoing Diagnosis Related Group (DRG) 209 procedures (major joint and limb reconstruction procedures of the lower extremities) has been shown to have large, unexplained interhospital variations. STUDY DESIGN AND METHODS: Abstracted records of 2590 consecutive DRG 209 patients at five university hospitals from January 1992 to December 1993 were stratified by procedure and preoperative blood deposit status. Patient characteristics and transfusion and in-hospital outcomes were compared across hospitals. RESULTS: Blood use among patients who did not preoperatively deposit blood was similar across hospitals. Significant differences were found across hospitals for total hip replacement patients in the percentage of patients preoperatively depositing blood (59-80%), percentage of patients receiving transfusion(s) (51 to > 99%), the mean number of units collected per patient (1.6-2.9), and the mean number of unused autologous units per 100 patients (1-185). No significant differences were found in the percentage of those who deposited blood and then required allogeneic units. There was little variability in length of hospital stay or in last hematocrits. Findings were similar for total knee replacement patients. CONCLUSIONS: Interhospital variations in red cell use for primary total hip and knee reconstruction are primarily due to hospital-specific differences in autologous blood collection and transfusion.

Aged↗

Outcome of transfusion of K:11 erythrocytes in a patient with anti-K11 antibody.

BACKGROUND AND OBJECTIVES: The clinical significance of anti-K11 in red cell transfusion therapy is unknown. We report the outcome of transfusion of K:11 erythrocytes into a patient with a known anti-K11 antibody. MATERIALS AND METHODS: The patient was monitored clinically following transfusion of 11 units of K:11 erythrocytes. A red cell survival study with K:11 erythrocytes and a monocyte monolayer assay (MMA) were performed. RESULTS: No adverse clinical outcome was detected. The red cell survival study showed normal survival of K:11 erythrocytes, and the MMA showed no increase in reactive monocytes. CONCLUSION: These findings suggest that K:11 red cells can safely be transfused to individuals with anti-K11 antibody.

Adult↗

College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: laboratory monitoring of unfractionated heparin therapy.

OBJECTIVE: To review the state of the art as reflected in the medical literature and the consensus opinion of recognized experts in the field regarding the laboratory monitoring of unfractionated heparin therapy. DATA SOURCES, EXTRACTION AND SYNTHESIS: The authors made an extensive review of the literature. The draft manuscript was circulated to every participant in the consensus conference prior to the convening of the conference. Extensive discussion concerning all of the issues addressed in the manuscript as well as the resulting recommendations occurred. This information was then used to revise the manuscript into its final form. CONCLUSIONS: The resulting manuscript has 23 specific recommendations regarding preanalytic, analytic, and postanalytic phases of monitoring and testing for complications related to unfractionated heparin therapy. This report contains detailed discussion of these recommendations and includes literature citations that support them. A number of issues for which consensus could not be reached are also discussed. A method is provided to assist laboratories, particularly small laboratories, in providing clinicians with an appropriate therapeutic range for the activated partial thromboplastin time, the most commonly used test in monitoring heparin therapy.

Blood Coagulation Tests↗

Evaluation of a new protamine titration method to assay heparin in whole blood and plasma.

When unfractionated heparin is used for therapeutic anticoagulation, the heparin effect must be monitored to avoid thrombotic or hemorrhagic complications. The ability of a factor Xa inhibition (XaI) assay was compared with that of a low-level heparin protamine titration (LLHPT) assay to measure the concentration of heparin after heparin was added in vitro to specimens of plasma and whole blood. Heparin effect on the activated partial thromboplastin time also was assessed in the same specimens. The XaI and LLHPT assays had comparable precision and provided linear results over a wide range of heparin concentrations. Both assays slightly underestimated the total amount of heparin added to the specimens. The most rapid test was the whole blood LLHPT assay; this test therefore may be useful for bedside monitoring of heparin. A significant disadvantage of the LLHPT assay was the large sample size required to perform it. These results provide in vitro evidence that the XaI and LLHPT assays can provide equally precise monitoring of heparin concentration.

Anticoagulants↗

Brightness of uniform stabilized fields.

Brightness of uniform fields during normal and stabilized viewing was determined as a function of adapting luminance, field size, and luminance gradient of the edges of the adapting field. In one set of experiments, it was found that, over a range of adapting luminances from 6 to 9600 td, a uniformly-illuminated 7.5 deg hemifield appeared about 1 log unit brighter in normal viewing than when it was retinally-stabilized. In the second set of experiments, it was found that the loss of brightness due to stabilized viewing was significantly greater for large fields with raised cosine edges than for small fields with step edges. Both sets of results can be accounted for by a two-stage model of light adaptation previously proposed to account for the fading time of stabilized images.

Adaptation, Ocular↗

Determinants of red cell, platelet, plasma, and cryoprecipitate transfusions during coronary artery bypass graft surgery: the Collaborative Hospital Transfusion Study.

BACKGROUND: Very little is known about the determinants of blood transfusions in patients undergoing coronary artery bypass graft surgery. STUDY DESIGN AND METHODS: To identify factors that influenced the transfusion of red cells, platelets, plasma, and cryoprecipitate, statistical methods were used to study 2476 consecutive diagnosis-related group 106 and 107 patients in five teaching hospitals who underwent coronary artery bypass surgery between January 1, 1992, and June 30, 1993. RESULTS: The likelihood of red cell transfusion was significantly associated with 10 preoperative factors: 1) admission hematocrit, 2) the patient's age, 3) the patient's gender, 4) previous coronary artery bypass surgery, 5) active tobacco use, 6) catheterization during the same admission, 7) coagulation defects, 8) insulin-dependent diabetes with renal or circulatory manifestations, 9) first treatment of new episode of transmural myocardial infarction, and 10) severe clinical complications. Platelet and/or plasma transfusions were strongly associated with the dose of red cells transfused. Transfusion requirements and other in-hospital outcomes were associated with patient characteristics, surgical procedure (reoperation vs. primary procedure), and the conduits used for revascularization (venous graft only, venous and internal mammary artery graft, or internal mammary artery graft only). Blood resource use and donor exposures were evaluated with respect to the risk to patients of contracting hepatitis C virus and human immunodeficiency virus infections. CONCLUSION: The classification of coronary artery bypass graft patients on the basis of attributes known preoperatively and by conduits used yields subsets of patients with distinctly different transfusion requirements and in-hospital outcomes.

Age Factors↗

Low interinstrument variability of the international normalized ratio with the coagamate X2/Simplastin excel system.

Minimizing the interlaboratory variability of the International Normalized Ratio (INR) for patients receiving coumarin therapy will require local laboratory calibration of individual coagulation instrument/reagent systems. However, some laboratories possess multiple coagulation instruments of the same model, and it is unclear if each instrument would require separate calibration. To address this question, a controlled study was performed that examined the interinstrument variability of the INR on three separate Coagamate X2 coagulometers (Organon Teknika, Durham, NC) using the Simplastin Excel reagent (Organon Teknika) (International Sensitivity Index = 2.14). The interinstrument coefficient of variation (CV) of the INR among the three instruments was 3.4% and 3.5% for patient control plasmas (n = 20) and coumarin plasmas (n = 40, INR range 1.5-4.6), respectively. The number of discordant INRs between paired instruments (one INR within and one INR out of the therapeutic range, plus a difference of at lest 0.4 INR units) was very low (0%). The interinstrument INR CVs for three commercial quality control plasmas were 2.6% (INR = 0.92), 4.1% (INR = 2.1), and 6.3% (INR = 4.5), and correlated well with the low CVs for patient samples. This study showed that the Coagamate X2/Simplastin Excel system is capable of very low interinstrument INR variability, and surpasses the interlaboratory CVs reported in the literature. Formal calibration of a single instrument may be adequate for laboratories possessing multiple instruments of the same model.

Anticoagulants↗