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Biomedical subjects

J T Brandt

Publications and source records attributed to J T Brandt.

At least 19 recordsLinked to original sources
PubMed2004

Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a serious condition associated with sepsis. Clinical management of DIC is hampered by lack of clear diagnostic criteria. The International Society on Thrombosis and Haemostasis (ISTH) has proposed a diagnostic scoring algorithm for overt DIC based on routine laboratory tests. The objective was to assess a modified version of the ISTH scoring system and determine the effect of drotrecogin alfa (activated) (DrotAA, recombinant human activated protein C) on patients with DIC. The large database from the PROWESS clinical trial in severe sepsis was retrospectively used to assess a modified ISTH scoring system. Baseline characteristics and treatment effects of DrotAA were evaluated. At baseline, 29% (454/1568) of patients had overt DIC. Overt DIC was a strong predictor of mortality, independent of APACHE II score and age. Placebo-treated patients with overt DIC had higher mortality than patients without (43 vs. 27%). DrotAA-treated patients with overt DIC had a trend towards greater relative risk reduction in mortality than patients without (29 vs. 18%, P = 0.261) but both groups had greater relative risk reduction than placebo-treated patients. Serious bleeding rates during DrotAA infusion in patients with and without overt DIC were slightly increased (P = 0.498), compared with placebo, while clinically overt thrombotic events during the 28-day period were slightly reduced (P = 0.144). Modified ISTH overt DIC scoring may be useful as an independent assessment for identifying severe sepsis patients at high risk of death with a favorable risk/benefit profile for DrotAA treatment. Patients without overt DIC also received significant treatment benefit.

Adult↗
PubMed1999

Prevalence of the factor VLeiden mutation among autopsy patients with pulmonary thromboembolic disease using an improved method for factor VLeiden detection.

Activated protein C resistance caused by factor VLeiden mutation is the most common inherited predisposing cause of venous thromboembolism, including pulmonary embolism (PE). We studied whether the incidence of factor VLeiden is higher among patients with PE evident at autopsy than in the general population. Paraffin-embedded fixed tissue blocks from all autopsy patients with diagnosed pulmonary thromboembolic disease during a 4-year period were collected for DNA extraction. Extraction and molecular analysis of the DNA was performed with an improved technique with an internal control to determine the presence of factor VLeiden mutation. Analysis of 82 autopsy cases with PE yielded 5 patients who were heterozygotes. Seventy-seven of the 82 patients analyzed were normal, and no homozygotes for factor VLeiden mutation were identified. This yielded a positive rate of 6% overall and 7% among white patients, which is similar to the incidence of heterozygotes in the white population. This study indicates that routine determination of factor VLeiden mutation is not warranted for patients with PE diagnosed at autopsy.

Adolescent↗
PubMed1999

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↗
PubMed1998

The preoperative bleeding time test lacks clinical benefit: College of American Pathologists' and American Society of Clinical Pathologists' position article.

The major conclusions of this position article are as follows: (1) In the absence of a history of a bleeding disorder, the bleeding time is not a useful predictor of the risk of hemorrhage associated with surgical procedures. (2) A normal bleeding time does not exclude the possibility of excessive hemorrhage associated with invasive procedures. (3) The bleeding time cannot be used to reliably identify patients who may have recently ingested aspirin or nonsteroidal anti-inflammatory agents or those who have a platelet defect attributable to these drugs. The best preoperative screen to predict bleeding continues to be a carefully conducted clinical history that includes family and previous dental, obstetric, surgical, traumatic injury, transfusion, and drug histories. A history suggesting a possible bleeding disorder may require further evaluation; such an evaluation may include performance of the bleeding time test, as well as a determination of the platelet count, the prothrombin time, and the activated partial thromboplastin time. In the absence of a history of excessive bleeding, the bleeding time fails as a screening test and is, therefore, not indicated as a routine preoperative test.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Differential diagnosis of hereditary hemochromatosis from other liver disorders by genetic analysis: gene mutation analysis of patients previously diagnosed with hemochromatosis by liver biopsy.

BACKGROUND: Hereditary hemochromatosis, a common autosomal recessive trait caused by mutations in the HLA-H gene, is often diagnosed by the pathologist at the time of histologic examination. Unfortunately, histologic parameters alone do not differentiate between hereditary hemochromatosis and other causes of iron overload. We performed a retrospective study to determine the frequency of familial hemochromatosis in patients diagnosed with he mochromatosis by abnormal liver histology. METHODS AND RESULTS: DNA was isolated from paraffin-embedded tissue sections from 15 patients and used in a polymerase chain reaction-based assay in which we tested for the C282Y and H63D mutations. We found that in this group of patients, 5 (33%) were homozygous for the common C282Y genetic mutation, 3 (20%) were heterozygous, and 7 (47%) were normal. CONCLUSIONS: Our study shows that the molecular assay is the gold standard for the diagnosis of hereditary hemochromatosis. The case study also illustrates that a definitive diagnosis of familial hemochromatosis has significant counseling implications allowing for accurate family studies.

Adult↗
PubMed1998

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

OBJECTIVE: To review the state of the art of laboratory monitoring of oral anticoagulant therapy, as reflected by the medical literature and the consensus opinion of recognized experts in the field, and to make recommendations for improvement in laboratory monitoring of oral anticoagulant therapy. DATA SOURCES: Review of the medical literature, primarily from the last 10 years, and current laboratory practices by a panel of 8 international experts in the field of oral anticoagulant monitoring. DATA EXTRACTION AND SYNTHESIS: After an initial assessment of the literature, key points were identified. Experts were assigned to do an in-depth review of the literature and current practices relevant to each of the key points and to prepare a summary of their findings and recommendations. A draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy prior to the conference. Each of the key points and associated recommendations was then presented for discussion at the Conference. Recommendations were accepted if a consensus of the 26 experts attending the Conference was reached. The results of the discussion were used to revise the manuscript into its final form. CONCLUSIONS: Consensus was reached on 12 recommendations concerning the laboratory monitoring of oral anticoagulant therapy. Detailed discussion of the rationale for each of these recommendations is found in the text of this article. Discussion of points on which consensus was not reached is also included in the text. It is hoped that widespread adoption of these recommendations will further improve the laboratory monitoring of oral anticoagulant therapy.

Administration, Oral↗
PubMed1998

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↗
PubMed1997

Aberrant expression of CD19 as a marker of monocytic lineage in acute myelogenous leukemia.

Immunophenotypic analysis plays a critical role in the diagnosis and classification of acute leukemia. Certain characteristic immunophenotypic patterns have emerged that aid in the classification of acute myelogenous leukemia (AML). We describe a unique pattern of expression of CD19, a B cell-associated cell surface antigen, in cases of AML. We reviewed 59 cases of de novo AML to determine the pattern of CD19 expression in cases of AML using three different CD19 monoclonal antibodies, including B4 (Lytic), B4 89B (Coulter, Miami, Fla) and SJ25-C1 (GenTrak, Plymouth Meeting, Pa). We confirmed the known relationship between CD19 expression and t(8;21)-positive AML M2; in these cases, CD19 was detected with all three antibodies. We also found a unique pattern of CD19 expression in cases of AML with a substantial monocytic-monoblastic component. In 6 of 12 cases of AML M4 or M5, CD19 expression was evident only with the B4 (Lytic) antibody; CD19 expression was not observed using B4 89B or SJ25-C1. We did not observe any recurring chromosomal abnormalities in these cases of CD19-positive AML M4/M5; furthermore, none of these cases demonstrated a t(8;21). Using CD11b, CD14, and other myeloid markers, we found that AML M4 and AML M5 were characterized by dual populations of blasts. With the exception of a case of AML M4 eo, cases of AML M4 were associated with one population of blasts lacking both CD11b and CD14 and a second population with one or both of these antigens. Cases of AML M5 also had dual populations of blasts, but in contrast with AML M4, each population expressed CD11b, CD14, or both. Our findings suggest that specific immunophenotypic patterns, including the unique pattern of CD19 expression with the B4 (Lytic) monoclonal antibody, may prove useful in classifying cases of AML M4 and M5.

Adult↗
PubMed1996

The incidence of the gene for thermolabile methylene tetrahydrofolate reductase in African Americans.

Increased levels of homocysteine have been linked to both arterial and venous thromboembolic problems (1,2). Homocystinuria is a relatively rare disorder caused by a deficiency of cystathione synthase and is characterized by markedly increased levels of homocysteine and premature vascular disease (3-5). Epidemiological studies have suggested that mild elevations of homocysteine are also associated with vascular disease (2). Recent evidence suggests that a polymorphism of the gene encoding for 5,10-methylene tetrahydrofolate reductase (MTHFR) gives rise to a thermolabile form of the enzyme that is associated with increased levels of homocysteine when inherited as a homozygous trait (6). This polymorphism is due to a C --> T substitution at nucleotide 677 which converts an alanine to valine in a conserved portion of the molecule (6). The allele frequency for the thermolabile form of the enzyme was quite high (0.38) in a population of French Canadians. This polymorphism thus appears to be a common risk factor for increased plasma levels of homocysteine and vascular diseases. As the incidence of such genetic polymorphisms often varies among ethnic populations, we were interested in comparing the incidence of this polymorphism in Caucasians and African Americans.

Black or African American↗
PubMed1996

Phosphoinositide 3-kinase and p72syk noncovalently associate with the low affinity Fc gamma receptor on human platelets through an immunoreceptor tyrosine-based activation motif. Reconstitution with synthetic phosphopeptides.

Previously, we have demonstrated that the cytoplasmic tyrosine kinase p72syk is coupled to the platelet Fc receptor for IgG (Fc gamma RIIA) (Chacko, G. W., Duchemin, A. M., Coggeshall, K. M., Osborne, J. M., Brandt, J. T., and Anderson, C. L. (1994) J. Biol. Chem. 269, 32435-32440). Further analysis of the platelet activation by Fc gamma RIIA demonstrated that Fc gamma RIIA is also inducibly coupled to the serine/threonine and lipid kinase, phosphoinositide 3-kinase (PI 3-K). activation of platelets with anti-Fc gamma RIIA antibodies resulted in the noncovalent association of PI 3-K with Fc gamma RIIA as well as an increase in Fc gamma RIIA-associated PI 3-K activity. Binding of both p72syk and PI 3-K to Fc gamma RIIA was reconstituted with synthetic phosphopeptides corresponding to the sequence of the atypical immunoreceptor tyrosine-based activation motif (ITAM) in the cytoplasmic domain of Fc gamma RIIA. Our findings demonstrate that coupling of both p72syk and PI. 3-K activities to Fc gamma RIIA is regulated by tyrosine phosphorylation of the ITAM, and we speculate that p72syk might act as an adapter to recruit PI 3-K to activated Fc gamma RIIA.

Amino Acid Sequence↗
PubMed1996

The mechanism of platelet aggregation induced by HLA-related antibodies.

Immune-mediated platelet activation is emerging as an important pathogenic mechanism of thrombosis. In vitro studies have suggested two distinct pathways for immune-mediated platelet activation; one involving clustering of platelet Fc gamma RIIa, the other involving platelet-associated complement activation. HLA-related antibodies have been shown to cause platelet aggregation, but the mechanism has not been clarified. We evaluated the mechanism of platelet aggregation induced by HLA-related antibodies from nine patients. Antibody to platelet Fc gamma RIIa failed to block platelet aggregation with 8/9 samples, indicating that engagement of platelet Fc gamma RIIa is not necessary for the platelet aggregation induced by HLA-related antibodies. In contrast, platelet aggregation was blocked by antibodies to human C8 (5/7) or C9 (7/7). F(ab')2 fragments of patient IgG failed to induce platelet activation although they bound to HLA antigen on platelets. Intact patient IgG failed to aggregate washed platelets unless aged serum was added. The activating IgG could be adsorbed by incubation with lymphocytes and eluted from the lymphocytes. These results indicate that complement activation is involved in the aggregation response to HLA-related antibodies. This is the first demonstration of complement-mediated platelet aggregation by clinical samples. Five of the patients developed thrombocytopenia in relationship to blood transfusion and two patients developed acute thromboembolic disease, suggesting that these antibodies and the complement-dependent pathway of platelet aggregation may be of clinical significance.

Adult↗