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Biomedical subjects

Michael Laposata

Publications and source records attributed to Michael Laposata.

53 records · Page 3Linked to original sources
PubMed2003

Clinical significance of a borderline titer in a negative ELISA test for heparin-induced thrombocytopenia.

We studied the usefulness of repeated enzyme-linked immunosorbent assay testing for heparin-induced thrombocytopenia (HIT) when the initial test result was negative and sought to determine whether the titer of the initial negative result correlated with the likelihood of obtaining a positive test result in repeated testing. We divided 150 patients who underwent HIT testing into 3 groups (50 patients each): (1) very low titer negative (0.0%-33.3% of the threshold for a positive test); (2) low titer negative (33.4%-66.6% of the threshold); and (3) high titer negative (66.7%-99.9% of the threshold). Among the patients who underwent a repeat test, 5% (1/20) of group 1 patients, 13% (4/32) of group 2 patients, and 43% (13/30) of group 3 patients tested positive in the repeat test (P = .0026). Thus, nearly half of patients with initially negative HIT test results had positive results in the repeat test if the negative titer was 66.7% or more of the threshold. If laboratories report the HIT titer, rather than just negative or positive, the titer might help clinicians predict which patients have HIT despite a negative initial test, and the overall sensitivity for diagnosing HIT might be improved.

Antibodies↗
PubMed2003

Fatty acid ethyl esters. Ethanol metabolites that reflect ethanol intake.

Fatty acid ethyl esters (FAEEs) are nonoxidative ethanol metabolites that have been implicated as mediators of alcohol-induced organ damage. FAEEs are detectable in the blood after ethanol ingestion, and on that basis represent markers of ethanol intake. FAEEs have also been quantitated in human liver and adipose tissue and have been shown to be postmortem markers of premortem ethanol intake. A substantial difference in FAEE concentration was found in liver and adipose tissue of patients with detectable blood ethanol at the time of autopsy vs those with no detectable blood ethanol, who were either chronic alcoholics or social drinkers. Most currently available diagnostic markers for chronic alcoholism have limited clinical utility. Data in this report demonstrate that the amount or type of FAEEs can be used to differentiate a chronic alcoholic from an episodic heavy drinker (binage drinker) at or near peak blood ethanol concentrations and approximately 24 hours after discontinuation of ethanol. Thus, FAEEs are markers of ethanol intake in blood and tissues and can be useful in distinguishing chronic alcoholics from binge drinkers.

Alcoholic Intoxication↗
PubMed2003

The timing of a positive test result for heparin-induced thrombocytopenia relative to the platelet count and anticoagulant therapy in 43 consecutive cases.

We studied the timing of a positive heparin-induced thrombocytopenia (HIT) test result relative to changes in platelet count and anticoagulant use. We obtained platelet counts in 100 consecutive HIT+ cases before, during, and after heparin therapy; 43 cases met study criteria and were included in study part 1. In part 2, platelet counts at the time of the HIT test in 2 groups (100 each HIT+ and HIT- cases) were compared. In part 1, cases could be divided into 4 groups based on the diagnosis of HIT relative to platelet counts (1, within 1-2 days of a major drop in platelet count [11.6%]; 2, after > 2 days of a major fall in platelet count [41.9%]; 3, in patients with already low platelet counts [27.9%]; 4, after platelet count was rising [18.6%]). In study part 2, the mean platelet counts for the HIT+ and HIT- groups were almost identical. HIT should be suspected in any thrombotic patient who had a previous decline in platelet count, has a low platelet count, or has a rising platelet count after a previous decline in association with heparin exposure. In study part 2, 1 platelet count value at the time of the HIT test did not provide useful information.

Anticoagulants↗
PubMed2002

Enhanced clinical consulting--moving toward the core competencies of laboratory professionals.

The large menu of laboratory assays available today makes it increasingly difficult for the non-specialist to order all necessary tests, avoid medical errors, and still contain cost. Curbside consultations, "intelligent" laboratory information systems, and medical information from the Internet cannot fully fill the need for expert advice on test selection and interpretation of laboratory results. In this communication, we show the need for a more active role for laboratory physicians to select and interpret tests, demonstrate that existing attempts to deal with this issue are insufficient, and describe the model system which we have instituted at our institution. We combine reflexive testing algorithms with narrative interpretations provided by medical laboratory professionals and thereby enable physicians to obtain relevant laboratory results and to arrive at a definitive diagnosis without having to order individual tests. In our experience, such an arrangement can significantly improve the quality of care and reduce the cost per case by decreasing the time to diagnosis, the number of tests ordered, and the number of patient visits. In addition, interpretations provide a new source of professional revenue for the expert laboratory physician. This leads to a new role for laboratory professionals, in which their expertise in the selection and interpretation of laboratory tests is fully utilized.

Algorithms↗
PubMed2002

Hypercoagulability test strategies in the protein C and protein S pathway.

The protein C-protein S pathway is critical in controlling normal clot formation to provide homeostasis between thrombosis and hemorrhage. Abnormalities have been described in which the pathway is altered because factor V cannot be degraded by activated protein C, producing activated protein C resistance. It has been known for nearly two decades that deficiencies in protein C and protein S can result in impaired inhibition of clot formation resulting in increased risk for thrombosis. This article describes the testing strategies associated with the diagnosis of activated protein C resistance, protein C deficiency, and protein S deficiency.

Algorithms↗
PubMed2002

Elevated concentrations of free fatty acids are associated with increased insulin response to standard glucose challenge in human immunodeficiency virus-infected subjects with fat redistribution.

Fat redistribution, defined by both increased abdominal visceral fat and/or decreased abdominal, extremity, and facial subcutaneous fat, is increasingly recognized among human immunodeficiency virus (HIV)-infected patients treated with combination antiretroviral therapy. Fat redistribution in this population is associated with insulin resistance and dyslipidemia and is often referred to as the HIV lipodystrophy syndrome (LIPO). Fatty acids are known to modulate insulin resistance in other disease states, but a comprehensive evaluation of fatty acids has not been undertaken among HIV-infected patients with fat redistribution. In this study, we investigated fatty acid concentrations in 64 HIV-infected individuals (45 men and 19 women) with evidence of fat redistribution (LIPO) in comparison to 30 HIV-infected individuals (20 men and 10 women) without evidence of fat redistribution (NONLIPO) and 32 HIV-negative healthy control subjects (C) (21 males and 11 females) of similar age and body mass index (BMI). Glucose, insulin, and free fatty acid (FFA) levels were measured in response to a 75-g oral glucose tolerance test (OGTT) in the LIPO, NONLIPO, and C subjects. In addition, fasting lipids were obtained, and body composition was determined by anthropometric measurements and dual-energy x-ray absorptiometry (DXA). Fasting FFA concentrations were significantly increased in the LIPO group as compared with NONLIPO and C subjects (0.74 +/- 0.03 v 0.60 +/- 0.04 [mean +/- SEM] mmol/L, P =.002, LIPO v NONLIPO; 0.74 +/- 0.03 v 0.59 +/- 0.03 mmol/L, P =.001, LIPO v C). In contrast, fasting FFA concentrations were not increased in the NONLIPO group (0.60 +/- 0.04 v 0.59 +/- 0.03, P =.909, NONLIPO v C). Similarly, fasting triglycerides and 120-minute OGTT FFA were significantly increased in the LIPO group as compared with the NONLIPO and C group. FFA decreased in HIV-infected LIPO, NONLIPO, and C subjects in response to OGTT, but the 120-minute FFA concentrations remained significantly elevated in LIPO patients compared with NONLIPO and C subjects. In a multivariate regression model of LIPO patients, fasting FFA (P =.027) was a strong independent predictor of insulin area under the curve (AUC), controlling for age, BMI, gender, and body composition (r(2) for model =.31). No differences were observed in FFA concentrations in the LIPO group in an analysis based on current protease inhibitor (PI) use. These data suggest that FFA concentrations are increased in HIV-infected patients with fat redistribution. Increased fasting concentrations of fatty acids are associated with abnormal insulin responses to standard glucose challenge in HIV-infected patients with fat redistribution. Further studies are necessary to determine the mechanism of increased fatty acid concentrations and the role played by increased FFA in mediating insulin resistance in this population.

Absorptiometry, Photon↗
PubMed2002

Alcoholic pancreatitis in rats: injury from nonoxidative metabolites of ethanol.

The mechanism by which alcohol injures the pancreas remains unknown. Recent investigations suggest a role for fatty acid ethyl ester (FAEE), a nonoxidative metabolite of ethanol, in the pathogenesis of alcohol pancreatitis. In this study, we characterized ethanol-induced injury in rats and evaluated the contribution of oxidative and nonoxidative ethanol metabolites in this form of acute pancreatitis. Pancreatic injury in rats was assessed by edema, intrapancreatic trypsinogen activation, and microscopy after infusing ethanol with or without inhibitors of oxidative ethanol metabolism. Plasma and tissue levels of FAEE and ethanol were measured and correlated with pancreatic injury. Ethanol infusion generated plasma and tissue FAEE and, in a dose-dependent fashion, induced a pancreas-specific injury consisting of edema, trypsinogen activation, and formation of vacuoles in the pancreatic acini. Inhibition of the oxidation of ethanol significantly increased both FAEE concentration in plasma and pancreas and worsened the pancreatitis-like injury. This study provides direct evidence that ethanol, through its nonoxidative metabolic pathway, can produce pancreas-specific toxicity in vivo and suggests that FAEE are responsible for the development of early pancreatic cell damage in acute alcohol-induced pancreatitis.

Alcohol Dehydrogenase↗
PubMed2002

Laboratory diagnosis of dysfibrinogenemia.

Dysfibrinogenemia is a coagulation disorder caused by a variety of structural abnormalities in the fibrinogen molecule that result in abnormal fibrinogen function. It can be inherited or acquired. The inherited form is associated with increased risk of bleeding, thrombosis, or both in the same patient or family. Traditionally, dysfibrinogenemia is diagnosed by abnormal tests of fibrin clot formation; the thrombin time and reptilase time are the screening tests, and the fibrinogen clotting activity-antigen ratio is the confirmatory test. The inherited form is diagnosed by demonstrating similar laboratory test abnormalities in family members, and if necessary by analysis of the fibrinogen protein or fibrinogen genes in the patient. The acquired form is diagnosed by demonstrating abnormal liver function tests and by ruling out dysfibrinogenemia in family members. This article reviews the laboratory testing of dysfibrinogenemia and presents an algorithm for sequential test selection that can be used for diagnosis.

Algorithms↗
PubMed2002

Activated protein C resistance, the factor V Leiden mutation, and a laboratory testing algorithm.

OBJECTIVES: To present the current understanding of factor V Leiden and activated protein C resistance, and to propose a laboratory testing algorithm. DATA SOURCES: Publications on MEDLINE with the terms factor V Leiden or activated protein C resistance through mid 2001, as well as publications in the authors' files, were screened for inclusion in this report. STUDY SELECTION: Original studies that report a novel finding on testing or clinical features of activated protein C resistance or factor V Leiden are included. Data Extraction.-The novel or key findings from the selected studies are analyzed. DATA SYNTHESIS: Protein C and protein S are the integral components of an anticoagulation pathway that limits fibrinogen conversion to fibrin through the degradation of factors Va and VIIIa. When factor Va is resistant to degradation by activated protein C, this anticoagulation pathway does not operate properly, and patients have an increased risk for thrombosis. This report describes the protein C/protein S pathway, the significance of activated protein C resistance and the factor V Leiden mutation, and the clinical testing used to detect activated protein C resistance and the factor V Leiden mutation. A proposed laboratory testing algorithm is also provided. CONCLUSIONS: Factor V Leiden is a risk factor for venous thrombosis and it is particularly common in white populations. A laboratory testing algorithm is proposed.

Activated Protein C Resistance↗
PubMed2002

Laboratory evaluation of hypercoagulability with venous or arterial thrombosis.

OBJECTIVE: To provide recommendations for hypercoagulation testing for patients with venous, arterial, or neurovascular thrombosis, as reflected in the medical literature and the consensus opinion of recognized experts in the field. DATA SOURCES, EXTRACTION, AND SYNTHESIS: The authors extensively examined the literature and current practices, and prepared a draft manuscript with preliminary recommendations. The draft manuscript was circulated to each of the expert participants (n = 30) in the consensus conference prior to the convening of the conference. The manuscript and recommendations were then presented at the conference for discussion. Recommendations were accepted if a consensus of the 28 experts attending the conference was reached. The discussions were also used to revise the manuscript into its final form. CONCLUSIONS: The resulting article provides 17 recommendations for hypercoagulation testing in the setting of venous, arterial, or neurovascular thrombosis. The supporting evidence for test selection is analyzed and cited, and consensus recommendations for test selection are presented. Issues for which a consensus was not reached at the conference are also discussed.

Arteries↗
PubMed2002

Diagnostic studies for thrombophilia in women on hormonal therapy and during pregnancy, and in children.

OBJECTIVE: To review the role of acquired and inherited prothrombotic risk factors that increase the risk of thrombosis in oral contraceptive users, during pregnancy, and in neonates, infants, and children; and to determine by the consensus opinion of recognized experts in the field which risk factors should be determined in which individuals at which time. DATA SOURCES: Review of the medical literature and current clinical practice by a panel of experts in the field of thrombophilia. DATA EXTRACTION AND SYNTHESIS: The experts made an extensive review of the published literature and prepared a draft manuscript, which included preliminary recommendations. The draft manuscript was circulated to participants in the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia prior to the conference. The manuscript and recommendations were then presented at the conference for discussion. 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: This report reviews the options for testing for thrombophilic states in women using oral contraceptives, during pregnancy, and in neonates and children. General guidelines for testing in these clinical situations are provided, along with citation of the appropriate supporting literature.

Abortion, Habitual↗
PubMed2002

Liver and adipose tissue fatty acid ethyl esters obtained at autopsy are postmortem markers for premortem ethanol intake.

BACKGROUND: Fatty acid ethyl esters (FAEEs) are nonoxidative ethanol metabolites that have been implicated as mediators of alcohol-induced organ damage. FAEEs are detectable in the blood after ethanol ingestion, and on that basis have been proposed as markers of ethanol intake. Because blood is not always available at autopsy, in this study we quantified FAEEs in human liver and adipose tissue as potential postmortem markers of premortem ethanol intake. METHODS: Twenty-four sets of samples were collected at the Massachusetts State Medical Examiner's Office, and 7 sets of samples were obtained from the Pathology Department of Massachusetts General Hospital. Samples of liver and adipose tissue were collected at autopsy, and FAEEs were isolated and quantified from these organs as mass per gram of wet weight. Postmortem analysis of blood involved assessment for ethanol and other drugs. RESULTS: The study shows a substantial difference in FAEE concentrations in liver and adipose tissue of patients with detectable blood ethanol at the time of autopsy vs those with no detectable blood ethanol, who were either chronic alcoholics or social drinkers. In addition, a specific FAEE, ethyl arachidonate, was found at concentrations >200 pmol/g almost exclusively in the liver and adipose tissue of individuals with detectable blood ethanol at the time of death, providing an additional FAEE-related marker for prior ethanol intake. CONCLUSIONS: The mass of FAEEs in liver and adipose tissue and the presence of ethyl arachidonate can serve as postmortem markers of premortem ethanol intake when no blood sample can be obtained.

Adipose Tissue↗
PubMed2002

Pathogenesis of alcoholic liver disease--recent advances.

The article summarizes the proceedings of a symposium on recent advances in research on the pathogenesis of alcoholic liver disease at the 2001 RSA meeting in Montreal, Canada. The chairs were Amin A. Nanji and Samuel W. French. The presentations were (1) Role of inflammatory mediators in alcoholic liver injury by Amin A. Nanji, (2) Role of endotoxin, lipopolysaccharide binding protein, CD14 and Toll receptors in alcoholic liver injury by Grace Su, (3) Fatty acid ethyl esters: toxicity, metabolism and markers of ethanol intake by Michael Laposata, and (4) Cyclic changes in gene expression when rats are fed alcohol at a constant rate by Samuel W. French.

Acyltransferases↗
PubMedDate not supplied

Fatty acid ethyl esters: recent observations.

Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, have been shown to be mediators of ethanol-induced cell injury and their presence in the blood and tissues is a marker of ethanol intake. Recently, it has been shown that FAEE are produced within seconds of infusion of ethanol into the heart, when using a protocol similar to that used for myocardial ablation. This raises the possibility that the mechanism for the death of myocytes in cardiac ablation involves the generation of toxic FAEE. It has also been recently demonstrated that chronic alcoholics have a high concentration of a specific FAEE species--ethyl oleate. The use of the serum ethyl oleate concentration may be helpful in differentiating binge drinkers from chronic alcoholics.

Alcoholism↗
PubMedDate not supplied

Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells.

BACKGROUND: Current evidence from both experimental and human studies indicates that omega-6 polyunsaturated fatty acids (n-6 PUFAs) promote breast tumor development, whereas long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) exert suppressive effects. The ratio of n-6 to n-3 fatty acids appears to be an important factor in controlling tumor development. Human cells usually have a very high n-6/n-3 fatty acid ratio because they cannot convert n-6 PUFAs to n-3 PUFAs due to lack of an n-3 desaturase found in C. elegans. MATERIALS AND METHODS: Adenoviral strategies were used to introduce the C. elegans fat-1 gene encoding an n-3 fatty acid desaturase into human breast cancer cells followed by examination of the n-6/n-3 fatty acid ratio and growth of the cells. RESULTS: Infection of MCF-7 cells with an adenovirus carrying the fat-1 gene resulted in a high expression of the n-3 fatty acid desaturase. Lipid analysis indicated a remarkable increase in the levels of n-3 PUFAs accompanied with a large decrease in the contents of n-6 PUFAs, leading to a change of the n-6/n-3 ratio from 12.0 to 0.8. Accordingly, production of the eicosanoids derived from n-6 PUFA was reduced significantly in cells expressing the fat-1 gene. Importantly, the gene transfer induced mass cell death and inhibited cell proliferation. CONCLUSION: The gene transfer of the n-3 fatty acid desaturase, as a novel approach, can effectively modify the n-6/n-3 fatty acid ratio of human tumor cells and provide an anticancer effect, without the need of exogenous n-3 PUFA supplementation. These data also increase the understanding of the effects of n-3 fatty acids and the n-6/n-3 ratio on cancer prevention and treatment.

Adenoviridae↗