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Biomedical subjects

G W Moore

Publications and source records attributed to G W Moore.

At least 19 recordsLinked to original sources

Low frequency of elevated prothrombin times in patients with lupus anticoagulants when using a recombinant thromboplastin reagent: implications for dosing and monitoring of oral anticoagulant therapy.

Many patients with lupus anticoagulants (LA) are treated with oral anticoagulation and monitored using the international normalised ratio (INR) derived from the prothrombin time (PT). Recent reports have produced conflicting conclusions about the extent to which LA interferes with PT determination. The degree of anticoagulation may be overestimated in a patient whose LA affects the PT. A number of reports conclude that specific thromboplastin reagents containing recombinant tissue factor are sensitive to the presence of LAs and should not be used to monitor oral anticoagulant therapy in these patients. These studies were performed on orally anticoagulated patients. The present retrospective study on 400 patients with LAs who were not receiving therapeutic anticoagulation was performed to ascertain the frequency of prolonged PT in these patients when using Innovin recombinant thromboplastin. Only 17 (4.3%) out of 400 had prolonged PT in the presence of LA. As this is a low prevalence, and not all patients with LAs will require anticoagulant therapy, it is concluded that baseline INR determination should be used to highlight the need to monitor individual patients with LA-insensitive reagents. As the use of moderate-intensity oral anticoagulation for patients with LAs and previous thrombosis is receiving wider acceptance, an informed approach to anticoagulant monitoring will reduce the possibility of under-anticoagulating patients receiving this therapy.

Administration, Oral↗

A new-generation dilute Russell's viper venom time assay system for lupus anticoagulants: evaluation of detection utilising frozen reagents and controls.

The dilute Russell's viper venom time (DRVVT) is one of the most widely used assays to detect lupus anticoagulants (LAs). Variation in diagnostic performance exists between DRVVT reagents from various manufacturers due to a variety of factors such as antibody heterogeneity, reagent phospholipid composition, venom heterogeneity, assay methodology and analytical technique. Recently, a new-generation DRVVT assay system has become available that utilises frozen reagents and controls that offer potential benefits to the diagnostic laboratory in terms of reagent quality and convenience of use. This study evaluates the diagnostic and analytical performance of these CryoCheck reagents and controls on a commonly employed automated coagulation analyser, the Sysmex CA 1500. Sensitivity is assessed by analysis of 60 samples shown to contain LAs by combinations of an alternative DRVVT, LA-sensitive dilute activated partial thromboplastin time and activated seven lupus anticoagulant assay. Specificity is assessed using 30 samples negative for LA, eight plasmas from non-LA orally anticoagulated patients and also immunodepleted factor-deficient plasmas. The CryoCheck reagents generated comparable diagnostic performance data to that previously reported for other reagents. There was a marked improvement in sensitivity when the BCSH recommended percent correction of ratio calculation for assessment of phospholipid dependence was employed in place of the manufacturer suggested test/confirm ratio. Slightly better diagnostic performance was achieved when using a frozen pooled normal control in place of a lyophilised normal control to generate sample/control ratios, giving sensitivity, specificity, positive predictive and negative predictive values of 88.2%, 86.8%, 90% and 85.2%, respectively. The combination of CryoCheck reagents and the Sysmex CA 1500 analyser provides a sensitive and specific LA detection technique comparable to those currently available.

Freezing↗

Alteration in the laboratory profile of a lupus anticoagulant in a patient with non-Hodgkin's lymphoma.

We describe a patient with non-Hodgkin's lymphoma who developed a lupus anticoagulant (LA) detectable by activated partial thromboplastin time (APTT), dilute Russell's viper venom time (DRVVT) and kaolin clotting time (KCT). IgM anticardiolipin antibodies (ACA) were elevated. At a later admission, and following treatment for the lymphoma, routine coagulation screening showed an elevated prothrombin time (PT) without correction in mixing tests using a recombinant thromboplastin. Routine APTT was below the reference range and ACA levels were normal. Raw data for one-stage factor assays demonstrated the presence of an inhibitor. Analysis for LA was undertaken by DRVVT, KCT, activated seven lupus anticoagulant assay, Taipan snake venom time, platelet neutralisation procedures (PNP), Ecarin time and PT using rabbit brain thromboplastin. The results revealed a LA capable of prolonging the clotting times of the PNPs and PT using recombinant thromboplastin, but that was corrected using Ecarin venom, modified PNP and brain thromboplastin. The antibody also demonstrated the lupus anticoagulant co-factor effect. The factor VIII: C was markedly raised which may have masked the LA in the APTT. The changing laboratory profile over time demonstrates the effects of LA heterogeneity and variations in sensitivity and specificity of assays for the detection of antiphospholipid antibodies.

Aged↗

The Activated Seven Lupus Anticoagulant (ASLA) assay: a new test for lupus anticoagulants (LAs). Evidence that some LAs are detectable only in extrinsic pathway-based assays.

Accurate and timely detection of lupus anticoagulants (LAs) is of diagnostic and prognostic importance due to the association of persistent LAs with thrombotic disease. In the present study, a sensitive and specific assay for LAs has been developed using recombinant activated factor VII to initiate in vitro coagulation. The Activated Seven Lupus Anticoagulant (ASLA) assay uses dilute brain-derived phospholipid in the screening test and a platelet neutralization procedure (PNP) in the confirmatory test. Tests are reported as ratios of patient clotting time to normal control clotting time and percentage correction by PNP assessed for abnormal ratios. Evaluation with 70 known LA-positive plasmas demonstrated higher detection rates than with individual assays from a wide range of commonly employed LA tests. The ASLA assay identified 61 of 70 (87%) known LAs, compared with 65.7% with the most sensitive of the other assays. The various LA assays were used to test 110 plasma samples from patients with thrombotic disease previously negative for LA. These experiments demonstrated that 18 of 110 (16.4%) contained LAs detectable only in extrinsic pathway-based assays, 10 of these by ASLA testing alone. ASLA testing showed high diagnostic precision and has the potential to make a significant contribution to LA detection.

Blood Coagulation Disorders↗

Intranet-based quality improvement documentation at the Veterans Affairs Maryland Health Care System.

The Pathology and Laboratory Medicine Service of the Veterans Affairs Maryland Health Care System is inspected biannually by the College of American Pathologists (CAP). As of the year 2000, all documentation in the Anatomic Pathology Section is available to all staff through the VA Intranet. Signed, supporting paper documents are on file in the office of the department chair. For the year 2000 CAP inspection, inspectors conducted their document review by use of these Web-based documents, in which each CAP question had a hyperlink to the corresponding section of the procedure manual. Thus inspectors were able to locate the documents relevant to each question quickly and efficiently. The procedure manuals consist of 87 procedures for surgical pathology, 52 procedures for cytopathology, and 25 procedures for autopsy pathology. Each CAP question requiring documentation had from one to three hyperlinks to the corresponding section of the procedure manual. Intranet documentation allows for easier sharing among decentralized institutions and for centralized updates of the laboratory documentation. These documents can be upgraded to allow for multimedia presentations, including text search for key words, hyperlinks to other documents, and images, audio, and video. Use of Web-based documents can improve the efficiency of the inspection process.

Databases, Factual↗

Improved detection of lupus anticoagulants by the dilute Russell's Viper venom time.

Accurate and timely detection of lupus anticoagulants (LAs) is of diagnostic and prognostic importance due to the association of persistent LAs with thrombotic disease. A review of LA screening results by kaolin clotting time and dilute Russell's Viper venom time (dRVVT) on 2843 patient samples demonstrated that only 40.7% (417 of 1024) of elevated dRVVT ratios could be interpreted as consistent with the presence of an LA by confirmatory procedures. Apart from those due to the effects of anticoagulant therapy, the remainder generated inconclusive interpretations, necessitating significant numbers of costly repeat investigations. Manipulation of dRVVT assay conditions by increasing confirmatory reagent concentration, and altering venom concentration to maintain analytical parity with the standard assay, revealed LAs not fully neutralized by confirmatory tests at standard concentrations. Further experiments were performed using Russell's Viper venom reagents from five different manufacturers to demonstrate that the findings were not a reagent-specific phenomenon. Higher detection rates were achieved using multiple conventional assays but samples remained that required a modified confirmatory test to demonstrate LA activity. A previously unreported group of LAs was identified with raised dRVVT ratios that failed to correct with any of the dRVVT assays but demonstrated significant correction with all reagents in the modified confirmatory test. Use of modified confirmatory tests enhances sensitivity and specificity, and doubles LA detection rates by dRVVT. Adoption of the technique will significantly increase cost-effectiveness of LA detection in clinical practice.

Animals↗

Practice guidelines for autopsy pathology: autopsy reporting. Autopsy Committee of the College of American Pathologists.

The Autopsy Committee of the College of American Pathologists has prepared this revised guideline to reflect changes that have occurred in the reporting of autopsies since the original guideline was published in February 1995. It is intended to be an instrument to assist pathologists in the reporting of autopsies. The guideline is to be regarded as being primarily an educational tool. Application of these recommendations on autopsy reporting is to be made on the basis of the judgment of the pathologist engaged in a specific case.

Autopsy↗

U.S. Senate Bill 422: the Genetic Confidentiality and Nondiscrimination Act of 1997.

On March 11, 1997, Senator Pete Domenici introduced U.S. Senate Bill 422, the Genetic Confidentiality and Non-Discrimination Act of 1997. The bill specifies that "existing legal protections for genetic information are inadequate to ensure genetic privacy and to prevent genetic discrimination." The first stated purpose of the bill is "to define the circumstances under which DNA samples may be collected, stored, and analyzed and genetic information may be collected, stored, analyzed, and disclosed." The bill reinforces statutes already passed in 19 states that guarantee patients certain rights of control over their own personal genetic information (Congressional Record, S2141). This bill fundamentally changes the mechanism whereby molecular biologists acquire tissue, and defines new obligations between researchers and human subjects. Even if this bill is not passed in its present form, it appears inevitable that legislation with a similar intent will soon emerge. Any such legislation will carry the full weight and penalties of law. Because many current research practices may violate these proposed new regulations, researchers should understand the provisions of S. 422. Furthermore, it is crucial that researchers understand the bill now, before it becomes law, because this may be their last opportunity to lobby for any modifications of the bill.

Confidentiality↗

A prototype Internet autopsy database. 1625 consecutive fetal and neonatal autopsy facesheets spanning 20 years.

OBJECTIVE: To demonstrate that cause-of-death statements can be generated by a computer algorithm from an autopsy database composed of diagnostic terms. DATA SOURCES: Over 49 000 autopsy facesheets contributed by over a dozen institutions were collected from a publicly accessible Internet autopsy database. This database is available at the following web site: http:@www.med.jhu.edu/pathology/iad.html STUDY SELECTION: To test the feasibility of creating and using a publicly available autopsy database, and to identify the technical and medicolegal problems that may arise with such a novel resource, a prototype study was designed by selecting autopsy facesheets from fetal and neonatal deaths. An algorithm was developed to determine the cause of death from the listing of anatomic diagnoses. DATA EXTRACTION: One thousand six hundred twenty-five fetal and neonatal autopsy facesheets were selected encompassing fetal and neonatal deaths occurring up to 28 days after birth. DATA SYNTHESIS: The algorithm determined causes of death from autopsy facesheet data in all cases. On review by an experienced pediatric pathologist, these automatically generated cause-of-death statements required no modification or only slight modification in over 90% of cases. CONCLUSIONS: A large multi-institutional autopsy database composed of demographic and diagnostic information has been deposited on the Internet. This information can be freely downloaded and used by any researcher without violating patient confidentiality. As a demonstration of one possible application of the database, fetal and neonatal autopsies generated cause-of-death statements using a computer algorithm. One can anticipate that the wealth of information contained in autopsy facesheets can be assembled into a database that will serve the public interest.

Algorithms↗

SNOMED-encoded surgical pathology databases: a tool for epidemiologic investigation.

Pathology departments have invested considerable energy, sometimes extending over several decades, toward coding their anatomic pathology reports. As a result of these labors, there is now a vast amount of electronically coded data from surgical pathology reports, holding a wealth of information relevant to virtually every recognized pathologic entity. The original intent of the Systematized Nomenclature of Medicine (SNOMED) was to prepare population-based disease data from pathology reports, but no such studies have emerged in the medical literature. This is due in part to the nonuniform, idiosyncratic, and incomplete manner in which most SNOMED databases are constructed. Automatic (computer-driven) coding provides uniformity and completeness of SNOMED databases and offers the possibility of customized recoding for an entire collection of reports using any nomenclature and any set of coding algorithms. In prior investigations, we described a computer program that SNOMED-codes surgical pathology reports, and we provided an analysis of a large surgical pathology SNOMED database. In this report, we describe the importance of coded surgical pathology databases for research, teaching, hospital administration, and public health, and we explain the functional differences between coded databases and free-text collections of surgical pathology data. Surgical pathology departments and vendors of laboratory information systems can ensure that surgical report files can be automatically coded or recoded with any chosen nomenclature by adhering to simple guidelines.

Disease↗

Elevated prostate-specific antigen levels in black men and white men.

The usual ranges for prostate-specific antigen (PSA) are derived from a community-based population of White men but are used for screening on all men on the assumption that the differences between the PSA levels of different racial groups are small or have no clinical significance. Recently published reports, however, suggest that PSA levels in a specific racial population may vary directly with the relative risk of prostatic cancer within that population. PSA ranges were determined in Black and White men registered with the Veterans Affairs Maryland Health Care System, Baltimore, Maryland. The total patient census of 122,602 has near-equal numbers of Black and White men and maintains records of race designation for inpatients. Among the male patients with no known prostatic cancer, there were 10,808 men 40 years of age or older and 19,482 PSA test results. In this group, there were 3274 men identified as Black; 2993 identified as White, Not of Hispanic Origin, and 4541 identified as Other Race or Race Unknown. The 95th percentile PSA values in Black men and White men 40 through 49 years of age were 2.80 ng/mL and 2.01 ng/mL, respectively; 50 through 59 years old, 5.40 ng/mL and 4.19 ng/mL, respectively; 60 through 69 years old, 9.59 ng/mL and 7.00 ng/mL, respectively; 70 through 79 years old, 15.45 ng/mL and 9.40 ng/mL, respectively; and for men older than 80 years of age, the 95th PSA values were 21.05 ng/mL in Black men and 18.25 ng/mL in White men. In every age group, Black men had a higher range (for the 95th percentile) than did White men. The largest difference was found in men 70 through 79 years old; in this age group, the ratio of the upper limit of PSA for Black men compared with White men was 1.6 ng/mL.

Adult↗

Maintaining patient confidentiality in the public domain Internet Autopsy Database (IAD).

The Internet provides the opportunity of permitting public access to large databases containing patient information that can be shared and utilized by epidemiologists, health planners, and medical researchers. Until now, large databases containing patient information have been held in strict confidence, with database access available only to approved researchers or to researchers with access limited to only specific portions of the database. The Internet Autopsy Database (IAD) consists of demographic and pathologic data from over 49,000 autopsies contributed by over a dozen academic medical institutions. Each autopsy record in the public database consists of a uniform set of demographics and SNOMED-compatible terms. To make the database publicly available, a strategy had to be devised that assured the privacy of every person included in the database. A key step involved translating the autopsy facesheets into a listing of SNOMED-compatible terms that effectively eliminated identifying terminology, replacing free text with a generic nomenclature that preserves diagnostic information. The entire database is available on the Internet at: http:@www.med.jhu.edu/pathology/iad.html

Autopsy↗